id string | task_type string | pipeline string | difficulty string | num_hops int64 | question string | context string | reasoning_chain dict | answer string | choices list | modalities list | modality_data list | evidence list | metadata unknown | path_confidence_score float64 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
co_mech_00101 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_058216.3(RAD51C):c.293dup (p.Phe99fs) affects the Interaction of NuRD complexes with transcription factors pathway, citing each molecular step. | NM_058216.3(RAD51C):c.293dup (p.Phe99fs) VARIANT_IN_GENE RAD51C -> RAD51C PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> MTA3 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> MTA3 GENE_PARTICIPATES_IN_PATHWAY Interaction of NuRD complexes with transcription factors | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_058216.3(RAD51C):c.293dup (p.Phe99fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_058216.3(RAD51C):c.293dup (p.Phe99fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_058216.3(RAD51C):c.293dup (p.Phe99fs) VARIANT_IN_GENE RAD51C -> RAD51C PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> MTA3 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> MTA3 GENE_PARTICIPATES_IN_PATHWAY Interaction of NuRD complexes with transcription factors | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "RAD51C",
"source_db": "UniProt",
"payload": {
"accession": "O43502",
"sequence": "MRGKTFRFEMQRDLVSFPLSPAVRVKLVSAGFQTAEELLEVKPSELSKEVGISKAEALETLQIIRRECLTNKPRYAGTSESHKKCTALELLEQEHTQGFIITFCSALDDILGGGVPLMKTTEICGAPGVGKT... | [
{
"source_db": "ClinVar",
"source_id": "RAD51C",
"text": "NM_058216.3(RAD51C):c.293dup (p.Phe99fs) VARIANT_IN_GENE RAD51C",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA1",
"text": "RAD51C PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1",
"confidence": 0.98
},
{
... | {
"variant": "NM_058216.3(RAD51C):c.293dup (p.Phe99fs)",
"pathway": "Interaction of NuRD complexes with transcription factors"
} | 0.811906 |
co_mech_00102 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000051.4(ATM):c.7836dup (p.Arg2613fs) affects the Regulation of PLK1 Activity at G2/M Transition pathway, citing each molecular step. | NM_000051.4(ATM):c.7836dup (p.Arg2613fs) VARIANT_IN_GENE ATM -> ATM GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Degradation -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Degradation -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Regulation of PLK1 Activity at G2/M Transition | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000051.4(ATM):c.7836dup (p.Arg2613fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000051.4(ATM):c.7836dup (p.Arg2613fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_000051.4(ATM):c.7836dup (p.Arg2613fs) VARIANT_IN_GENE ATM -> ATM GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Degradation -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Degradation -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Regulation of PLK1 Activity at G2/M Transition | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ATM",
"source_db": "UniProt",
"payload": {
"accession": "Q13315",
"sequence": "MSLVLNDLLICCRQLEHDRATERKKEVEKFKRLIRDPETIKHLDRHSDSKQGKYLNWDAVFRFLQKYIQKETECLRIAKPNVSASTQASRQKKMQEISSLVKYFIKCANRRAPRLKCQELLNYIMDTVKDSSNGA... | [
{
"source_db": "ClinVar",
"source_id": "ATM",
"text": "NM_000051.4(ATM):c.7836dup (p.Arg2613fs) VARIANT_IN_GENE ATM",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-6804757",
"text": "ATM GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Degradation",
"confidence... | {
"variant": "NM_000051.4(ATM):c.7836dup (p.Arg2613fs)",
"pathway": "Regulation of PLK1 Activity at G2/M Transition"
} | 1 |
co_mech_00103 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_002087.4(GRN):c.373C>T (p.Gln125Ter) affects the Regulation of TP53 Activity through Methylation pathway, citing each molecular step. | NM_002087.4(GRN):c.373C>T (p.Gln125Ter) VARIANT_IN_GENE GRN -> GRN GENE_ANNOTATED_WITH_GO_TERM protein stabilization -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM protein stabilization -> CHEK2 GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Activity through Methylation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_002087.4(GRN):c.373C>T (p.Gln125Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_002087.4(GRN):c.373C>T (p.Gln125Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_002087.4(GRN):c.373C>T (p.Gln125Ter) VARIANT_IN_GENE GRN -> GRN GENE_ANNOTATED_WITH_GO_TERM protein stabilization -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM protein stabilization -> CHEK2 GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Activity through Methylation | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "GRN",
"source_db": "UniProt",
"payload": {
"accession": "P28799",
"sequence": "MWTLVSWVALTAGLVAGTRCPDGQFCPVACCLDPGGASYSCCRPLLDKWPTTLSRHLGGPCQVDAHCSAGHSCIFTVSGTSSCCPFPEAVACGDGHHCCPRGFHCSADGRSCFQRSGNNSVGAIQCPDSQFECPD... | [
{
"source_db": "ClinVar",
"source_id": "GRN",
"text": "NM_002087.4(GRN):c.373C>T (p.Gln125Ter) VARIANT_IN_GENE GRN",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0050821",
"text": "GRN GENE_ANNOTATED_WITH_GO_TERM protein stabilization",
"confidence": 0.6
},
{
... | {
"variant": "NM_002087.4(GRN):c.373C>T (p.Gln125Ter)",
"pathway": "Regulation of TP53 Activity through Methylation"
} | 0.774597 |
co_mech_00104 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_013254.4(TBK1):c.1972_1973del (p.Leu658fs) affects the alectinib-resistant ALK mutants pathway, citing each molecular step. | NM_013254.4(TBK1):c.1972_1973del (p.Leu658fs) VARIANT_IN_GENE TBK1 -> TBK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ALK GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ALK GENE_PARTICIPATES_IN_PATHWAY alectinib-resistant ALK mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_013254.4(TBK1):c.1972_1973del (p.Leu658fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_013254.4(TBK1):c.1972_1973del (p.Leu658fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_conf... | NM_013254.4(TBK1):c.1972_1973del (p.Leu658fs) VARIANT_IN_GENE TBK1 -> TBK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ALK GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ALK GENE_PARTICIPATES_IN_PATHWAY alectinib-resistant ALK mutants | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_013254.4(TBK1):c.1972_1973del (p.Leu658fs)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr12",
"pos": 64497658,
"track": "phyloP100way",
"window": 20,
"scores": [
-0.233874,
... | [
{
"source_db": "ClinVar",
"source_id": "TBK1",
"text": "NM_013254.4(TBK1):c.1972_1973del (p.Leu658fs) VARIANT_IN_GENE TBK1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "TBK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"... | {
"variant": "NM_013254.4(TBK1):c.1972_1973del (p.Leu658fs)",
"pathway": "alectinib-resistant ALK mutants"
} | 0.774597 |
co_mech_00105 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_003482.4(KMT2D):c.15680_15693dup (p.Ile5232fs) affects the Attenuation phase pathway, citing each molecular step. | NM_003482.4(KMT2D):c.15680_15693dup (p.Ile5232fs) VARIANT_IN_GENE KMT2D -> KMT2D GENE_PARTICIPATES_IN_PATHWAY MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis -> CREBBP GENE_PARTICIPATES_IN_PATHWAY MLL4 and MLL3 complexes regulate expression of PPARG target genes i... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_003482.4(KMT2D):c.15680_15693dup (p.Ile5232fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_003482.4(KMT2D):c.15680_15693dup (p.Ile5232fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"e... | NM_003482.4(KMT2D):c.15680_15693dup (p.Ile5232fs) VARIANT_IN_GENE KMT2D -> KMT2D GENE_PARTICIPATES_IN_PATHWAY MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis -> CREBBP GENE_PARTICIPATES_IN_PATHWAY MLL4 and MLL3 complexes regulate expression of PPARG target genes i... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KMT2D",
"source_db": "UniProt",
"payload": {
"accession": "O14686",
"sequence": "MDSQKLAGEDKDSEPAADGPAASEDPSATESDLPNPHVGEVSVLSSGSPRLQETPQDCSGGPVRRCALCNCGEPSLHGQRELRRFELPFDWPRCPVVSPGGSPGPNEAVLPSEDLSQIGFPEGLTPAHLGEPG... | [
{
"source_db": "ClinVar",
"source_id": "KMT2D",
"text": "NM_003482.4(KMT2D):c.15680_15693dup (p.Ile5232fs) VARIANT_IN_GENE KMT2D",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-9841922",
"text": "KMT2D GENE_PARTICIPATES_IN_PATHWAY MLL4 and MLL3 complexes regulate ... | {
"variant": "NM_003482.4(KMT2D):c.15680_15693dup (p.Ile5232fs)",
"pathway": "Attenuation phase"
} | 1 |
co_mech_00106 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_001199397.3(NEK1):c.1991_1992del (p.Lys664fs) affects the PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling pathway, citing each molecular step. | NM_001199397.3(NEK1):c.1991_1992del (p.Lys664fs) VARIANT_IN_GENE NEK1 -> NEK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_PARTICIPATES_IN_PATHWAY PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001199397.3(NEK1):c.1991_1992del (p.Lys664fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001199397.3(NEK1):c.1991_1992del (p.Lys664fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edg... | NM_001199397.3(NEK1):c.1991_1992del (p.Lys664fs) VARIANT_IN_GENE NEK1 -> NEK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_PARTICIPATES_IN_PATHWAY PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "NEK1",
"source_db": "UniProt",
"payload": {
"accession": "Q96PY6",
"sequence": "MEKYVRLQKIGEGSFGKAILVKSTEDGRQYVIKEINISRMSSKEREESRREVAVLANMKHPNIVQYRESFEENGSLYIVMDYCEGGDLFKRINAQKGVLFQEDQILDWFVQICLALKHVHDRKILHRDIKSQNI... | [
{
"source_db": "ClinVar",
"source_id": "NEK1",
"text": "NM_001199397.3(NEK1):c.1991_1992del (p.Lys664fs) VARIANT_IN_GENE NEK1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "NEK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
... | {
"variant": "NM_001199397.3(NEK1):c.1991_1992del (p.Lys664fs)",
"pathway": "PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling"
} | 0.774597 |
co_mech_00107 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_007294.4(BRCA1):c.5277+2T>G affects the Recruitment of mitotic centrosome proteins and complexes pathway, citing each molecular step. | NM_007294.4(BRCA1):c.5277+2T>G VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CDK1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Recruitment of mitotic centrosome proteins and complexes | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007294.4(BRCA1):c.5277+2T>G",
"source_node_type": "VARIANT",
"source_node_label": "NM_007294.4(BRCA1):c.5277+2T>G",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source... | NM_007294.4(BRCA1):c.5277+2T>G VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CDK1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Recruitment of mitotic centrosome proteins and complexes | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA1",
"source_db": "UniProt",
"payload": {
"accession": "P38398",
"sequence": "MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNR... | [
{
"source_db": "ClinVar",
"source_id": "BRCA1",
"text": "NM_007294.4(BRCA1):c.5277+2T>G VARIANT_IN_GENE BRCA1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0006974",
"text": "BRCA1 GENE_ANNOTATED_WITH_GO_TERM DNA damage response",
"confidence": 0.6
},
{
"sour... | {
"variant": "NM_007294.4(BRCA1):c.5277+2T>G",
"pathway": "Recruitment of mitotic centrosome proteins and complexes"
} | 0.774597 |
co_mech_00108 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000179.3(MSH6):c.3849del (p.Thr1284fs) affects the Activation of gene expression by SREBF (SREBP) pathway, citing each molecular step. | NM_000179.3(MSH6):c.3849del (p.Thr1284fs) VARIANT_IN_GENE MSH6 -> MSH6 GENE_ANNOTATED_WITH_GO_TERM damaged DNA binding -> CREBBP GENE_ANNOTATED_WITH_GO_TERM damaged DNA binding -> CREBBP GENE_PARTICIPATES_IN_PATHWAY Activation of gene expression by SREBF (SREBP) | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000179.3(MSH6):c.3849del (p.Thr1284fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000179.3(MSH6):c.3849del (p.Thr1284fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000179.3(MSH6):c.3849del (p.Thr1284fs) VARIANT_IN_GENE MSH6 -> MSH6 GENE_ANNOTATED_WITH_GO_TERM damaged DNA binding -> CREBBP GENE_ANNOTATED_WITH_GO_TERM damaged DNA binding -> CREBBP GENE_PARTICIPATES_IN_PATHWAY Activation of gene expression by SREBF (SREBP) | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH6",
"source_db": "UniProt",
"payload": {
"accession": "P52701",
"sequence": "MSRQSTLYSFFPKSPALSDANKASARASREGGRAAAAPGASPSPGGDAAWSEAGPGPRPLARSASPPKAKNLNGGLRRSVAPAAPTSCDFSPGDLVWAKMEGYPWWPCLVYNHPFDGTFIREKGKSVRVHVQFF... | [
{
"source_db": "ClinVar",
"source_id": "MSH6",
"text": "NM_000179.3(MSH6):c.3849del (p.Thr1284fs) VARIANT_IN_GENE MSH6",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0003684",
"text": "MSH6 GENE_ANNOTATED_WITH_GO_TERM damaged DNA binding",
"confidence": 0.6
},
{
... | {
"variant": "NM_000179.3(MSH6):c.3849del (p.Thr1284fs)",
"pathway": "Activation of gene expression by SREBF (SREBP)"
} | 0.774597 |
co_mech_00109 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_007194.4(CHEK2):c.1238T>A (p.Leu413Ter) affects the Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition pathway, citing each molecular step. | NM_007194.4(CHEK2):c.1238T>A (p.Leu413Ter) VARIANT_IN_GENE CHEK2 -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Regulation of MITF-M-dependent genes involv... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007194.4(CHEK2):c.1238T>A (p.Leu413Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007194.4(CHEK2):c.1238T>A (p.Leu413Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_007194.4(CHEK2):c.1238T>A (p.Leu413Ter) VARIANT_IN_GENE CHEK2 -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Regulation of MITF-M-dependent genes involv... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CHEK2",
"source_db": "UniProt",
"payload": {
"accession": "O96017",
"sequence": "MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTLSSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKSCEYCFDEPLLKRT... | [
{
"source_db": "ClinVar",
"source_id": "CHEK2",
"text": "NM_007194.4(CHEK2):c.1238T>A (p.Leu413Ter) VARIANT_IN_GENE CHEK2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045893",
"text": "CHEK2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription... | {
"variant": "NM_007194.4(CHEK2):c.1238T>A (p.Leu413Ter)",
"pathway": "Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition"
} | 0.774597 |
co_mech_00110 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000535.7(PMS2):c.1086_1087del (p.Met362fs) affects the SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription pathway, citing each molecular step. | NM_000535.7(PMS2):c.1086_1087del (p.Met362fs) VARIANT_IN_GENE PMS2 -> Single allele VARIANT_IN_GENE PMS2 -> Single allele VARIANT_IN_GENE MYC -> MYC GENE_PARTICIPATES_IN_PATHWAY SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000535.7(PMS2):c.1086_1087del (p.Met362fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000535.7(PMS2):c.1086_1087del (p.Met362fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_conf... | NM_000535.7(PMS2):c.1086_1087del (p.Met362fs) VARIANT_IN_GENE PMS2 -> Single allele VARIANT_IN_GENE PMS2 -> Single allele VARIANT_IN_GENE MYC -> MYC GENE_PARTICIPATES_IN_PATHWAY SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PMS2",
"source_db": "UniProt",
"payload": {
"accession": "P54278",
"sequence": "MERAESSSTEPAKAIKPIDRKSVHQICSGQVVLSLSTAVKELVENSLDAGATNIDLKLKDYGVDLIEVSDNGCGVEEENFEGLTLKHHTSKIQEFADLTQVETFGFRGEALSSLCALSDVTISTCHASAKVGTR... | [
{
"source_db": "ClinVar",
"source_id": "PMS2",
"text": "NM_000535.7(PMS2):c.1086_1087del (p.Met362fs) VARIANT_IN_GENE PMS2",
"confidence": 1
},
{
"source_db": "ClinVar",
"source_id": "Single allele",
"text": "Single allele VARIANT_IN_GENE PMS2",
"confidence": 1
},
{
"sour... | {
"variant": "NM_000535.7(PMS2):c.1086_1087del (p.Met362fs)",
"pathway": "SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription"
} | 1 |
co_mech_00111 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_000546.6(TP53):c.646GTG[2] (p.Val218del) affects the Signaling by RAF1 mutants pathway, citing each molecular step. | NM_000546.6(TP53):c.646GTG[2] (p.Val218del) VARIANT_IN_GENE TP53 -> MAPK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> MAPK1 GENE_PARTICIPATES_IN_PATHWAY Signaling by RAF1 mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000546.6(TP53):c.646GTG[2] (p.Val218del)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000546.6(TP53):c.646GTG[2] (p.Val218del)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_000546.6(TP53):c.646GTG[2] (p.Val218del) VARIANT_IN_GENE TP53 -> MAPK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> MAPK1 GENE_PARTICIPATES_IN_PATHWAY Signaling by RAF1 mutants | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "TP53",
"source_db": "UniProt",
"payload": {
"accession": "P04637",
"sequence": "MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMF... | [
{
"source_db": "ClinVar",
"source_id": "TP53",
"text": "NM_000546.6(TP53):c.646GTG[2] (p.Val218del) VARIANT_IN_GENE TP53",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "MAPK1",
"text": "MAPK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53",
"confidence": 0.998
},
{
... | {
"variant": "NM_000546.6(TP53):c.646GTG[2] (p.Val218del)",
"pathway": "Signaling by RAF1 mutants"
} | 0.999333 |
co_mech_00112 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_001042492.3(NF1):c.1492A>T (p.Lys498Ter) affects the TBC/RABGAPs pathway, citing each molecular step. | NM_001042492.3(NF1):c.1492A>T (p.Lys498Ter) VARIANT_IN_GENE NF1 -> NF1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> HTT GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> HTT PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH OPTN -> OPTN GENE_PARTICIPATES_IN_PATHWAY TBC/RABGAPs | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001042492.3(NF1):c.1492A>T (p.Lys498Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001042492.3(NF1):c.1492A>T (p.Lys498Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_001042492.3(NF1):c.1492A>T (p.Lys498Ter) VARIANT_IN_GENE NF1 -> NF1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> HTT GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> HTT PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH OPTN -> OPTN GENE_PARTICIPATES_IN_PATHWAY TBC/RABGAPs | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "NF1",
"source_db": "UniProt",
"payload": {
"accession": "P21359",
"sequence": "MAAHRPVEWVQAVVSRFDEQLPIKTGQQNTHTKVSTEHNKECLINISKYKFSLVISGLTTILKNVNNMRIFGEAAEKNLYLSQLIILDTLEKCLAGQPKDTMRLDETMLVKQLLPEICHFLHTCREGNQHAAELR... | [
{
"source_db": "ClinVar",
"source_id": "NF1",
"text": "NM_001042492.3(NF1):c.1492A>T (p.Lys498Ter) VARIANT_IN_GENE NF1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0043065",
"text": "NF1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process",
"confide... | {
"variant": "NM_001042492.3(NF1):c.1492A>T (p.Lys498Ter)",
"pathway": "TBC/RABGAPs"
} | 0.814703 |
co_mech_00113 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_007126.5(VCP):c.1874G>C (p.Arg625Pro) affects the Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) pathway, citing each molecular step. | NM_007126.5(VCP):c.1874G>C (p.Arg625Pro) VARIANT_IN_GENE VCP -> VCP GENE_ANNOTATED_WITH_GO_TERM regulation of apoptotic process -> APOE GENE_ANNOTATED_WITH_GO_TERM regulation of apoptotic process -> APOE GENE_PARTICIPATES_IN_PATHWAY Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Gro... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007126.5(VCP):c.1874G>C (p.Arg625Pro)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007126.5(VCP):c.1874G>C (p.Arg625Pro)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_007126.5(VCP):c.1874G>C (p.Arg625Pro) VARIANT_IN_GENE VCP -> VCP GENE_ANNOTATED_WITH_GO_TERM regulation of apoptotic process -> APOE GENE_ANNOTATED_WITH_GO_TERM regulation of apoptotic process -> APOE GENE_PARTICIPATES_IN_PATHWAY Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Gro... | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_007126.5(VCP):c.1874G>C (p.Arg625Pro)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr9",
"pos": 35059623,
"track": "phyloP100way",
"window": 20,
"scores": [
7.87425,
0.... | [
{
"source_db": "ClinVar",
"source_id": "VCP",
"text": "NM_007126.5(VCP):c.1874G>C (p.Arg625Pro) VARIANT_IN_GENE VCP",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0042981",
"text": "VCP GENE_ANNOTATED_WITH_GO_TERM regulation of apoptotic process",
"confidence": 0.6
... | {
"variant": "NM_007126.5(VCP):c.1874G>C (p.Arg625Pro)",
"pathway": "Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)"
} | 0.774597 |
co_mech_00114 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_007294.4(BRCA1):c.5236C>G (p.His1746Asp) affects the Regulation of ornithine decarboxylase (ODC) pathway, citing each molecular step. | NM_007294.4(BRCA1):c.5236C>G (p.His1746Asp) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Neddylation -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY Neddylation -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY Regulation of ornithine decarboxylase (ODC) | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007294.4(BRCA1):c.5236C>G (p.His1746Asp)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007294.4(BRCA1):c.5236C>G (p.His1746Asp)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_007294.4(BRCA1):c.5236C>G (p.His1746Asp) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Neddylation -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY Neddylation -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY Regulation of ornithine decarboxylase (ODC) | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA1",
"source_db": "UniProt",
"payload": {
"accession": "P38398",
"sequence": "MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNR... | [
{
"source_db": "ClinVar",
"source_id": "BRCA1",
"text": "NM_007294.4(BRCA1):c.5236C>G (p.His1746Asp) VARIANT_IN_GENE BRCA1",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-8951664",
"text": "BRCA1 GENE_PARTICIPATES_IN_PATHWAY Neddylation",
"confidence": 1
},
... | {
"variant": "NM_007294.4(BRCA1):c.5236C>G (p.His1746Asp)",
"pathway": "Regulation of ornithine decarboxylase (ODC)"
} | 1 |
co_mech_00115 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_000465.4(BARD1):c.158+1G>C affects the Impaired BRCA2 binding to SEM1 (DSS1) pathway, citing each molecular step. | NM_000465.4(BARD1):c.158+1G>C VARIANT_IN_GENE BARD1 -> BARD1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2 -> BRCA2 GENE_PARTICIPATES_IN_PATHWAY Impaired BRCA2 binding to SEM1 (DSS1) | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000465.4(BARD1):c.158+1G>C",
"source_node_type": "VARIANT",
"source_node_label": "NM_000465.4(BARD1):c.158+1G>C",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_d... | NM_000465.4(BARD1):c.158+1G>C VARIANT_IN_GENE BARD1 -> BARD1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2 -> BRCA2 GENE_PARTICIPATES_IN_PATHWAY Impaired BRCA2 binding to SEM1 (DSS1) | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BARD1",
"source_db": "UniProt",
"payload": {
"accession": "Q99728",
"sequence": "MPDNRQPRNRQPRIRSGNEPRSAPAMEPDGRGAWAHSRAALDRLEKLLRCSRCTNILREPVCLGGCEHIFCSNCVSDCIGTGCPVCYTPAWIQDLKINRQLDSMIQLCSKLRNLLHDNELSDLKEDKPRKSLF... | [
{
"source_db": "ClinVar",
"source_id": "BARD1",
"text": "NM_000465.4(BARD1):c.158+1G>C VARIANT_IN_GENE BARD1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA2",
"text": "BARD1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2",
"confidence": 0.999
},
{
"source_db... | {
"variant": "NM_000465.4(BARD1):c.158+1G>C",
"pathway": "Impaired BRCA2 binding to SEM1 (DSS1)"
} | 0.999667 |
co_mech_00116 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_001101.5(ACTB):c.217C>T (p.His73Tyr) affects the RHOH GTPase cycle pathway, citing each molecular step. | NM_001101.5(ACTB):c.217C>T (p.His73Tyr) VARIANT_IN_GENE ACTB -> ACTB GENE_ANNOTATED_WITH_GO_TERM ATP binding -> VCP GENE_ANNOTATED_WITH_GO_TERM ATP binding -> VCP GENE_PARTICIPATES_IN_PATHWAY RHOH GTPase cycle | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001101.5(ACTB):c.217C>T (p.His73Tyr)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001101.5(ACTB):c.217C>T (p.His73Tyr)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_001101.5(ACTB):c.217C>T (p.His73Tyr) VARIANT_IN_GENE ACTB -> ACTB GENE_ANNOTATED_WITH_GO_TERM ATP binding -> VCP GENE_ANNOTATED_WITH_GO_TERM ATP binding -> VCP GENE_PARTICIPATES_IN_PATHWAY RHOH GTPase cycle | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ACTB",
"source_db": "UniProt",
"payload": {
"accession": "P60709",
"sequence": "MDDDIAALVVDNGSGMCKAGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQSKRGILTLKYPIEHGIVTNWDDMEKIWHHTFYNELRVAPEEHPVLLTEAPLNPKANREKMTQIMFETFNTPAMYV... | [
{
"source_db": "ClinVar",
"source_id": "ACTB",
"text": "NM_001101.5(ACTB):c.217C>T (p.His73Tyr) VARIANT_IN_GENE ACTB",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "ACTB GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"source... | {
"variant": "NM_001101.5(ACTB):c.217C>T (p.His73Tyr)",
"pathway": "RHOH GTPase cycle"
} | 0.774597 |
co_mech_00117 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000314.8(PTEN):c.2T>G (p.Met1Arg) affects the COPI-mediated anterograde transport pathway, citing each molecular step. | NM_000314.8(PTEN):c.2T>G (p.Met1Arg) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM synapse assembly -> MAPT GENE_ANNOTATED_WITH_GO_TERM synapse assembly -> MAPT PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TUBA4A -> TUBA4A GENE_PARTICIPATES_IN_PATHWAY COPI-mediated anterograde transport | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000314.8(PTEN):c.2T>G (p.Met1Arg)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000314.8(PTEN):c.2T>G (p.Met1Arg)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000314.8(PTEN):c.2T>G (p.Met1Arg) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM synapse assembly -> MAPT GENE_ANNOTATED_WITH_GO_TERM synapse assembly -> MAPT PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TUBA4A -> TUBA4A GENE_PARTICIPATES_IN_PATHWAY COPI-mediated anterograde transport | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PTEN",
"source_db": "UniProt",
"payload": {
"accession": "P60484",
"sequence": "MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVM... | [
{
"source_db": "ClinVar",
"source_id": "PTEN",
"text": "NM_000314.8(PTEN):c.2T>G (p.Met1Arg) VARIANT_IN_GENE PTEN",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0007416",
"text": "PTEN GENE_ANNOTATED_WITH_GO_TERM synapse assembly",
"confidence": 0.6
},
{
"sour... | {
"variant": "NM_000314.8(PTEN):c.2T>G (p.Met1Arg)",
"pathway": "COPI-mediated anterograde transport"
} | 0.812072 |
co_mech_00118 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000249.4(MLH1):c.1731+5_1731+6delinsCC affects the Anchoring of the basal body to the plasma membrane pathway, citing each molecular step. | NM_000249.4(MLH1):c.1731+5_1731+6delinsCC VARIANT_IN_GENE MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Anchoring of the basal body to the plasma membrane | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000249.4(MLH1):c.1731+5_1731+6delinsCC",
"source_node_type": "VARIANT",
"source_node_label": "NM_000249.4(MLH1):c.1731+5_1731+6delinsCC",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000249.4(MLH1):c.1731+5_1731+6delinsCC VARIANT_IN_GENE MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Anchoring of the basal body to the plasma membrane | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MLH1",
"source_db": "UniProt",
"payload": {
"accession": "P40692",
"sequence": "MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGK... | [
{
"source_db": "ClinVar",
"source_id": "MLH1",
"text": "NM_000249.4(MLH1):c.1731+5_1731+6delinsCC VARIANT_IN_GENE MLH1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"sour... | {
"variant": "NM_000249.4(MLH1):c.1731+5_1731+6delinsCC",
"pathway": "Anchoring of the basal body to the plasma membrane"
} | 0.774597 |
co_mech_00119 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000059.4(BRCA2):c.4658del (p.Thr1553fs) affects the TRAF6 mediated IRF7 activation pathway, citing each molecular step. | NM_000059.4(BRCA2):c.4658del (p.Thr1553fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CREBBP GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CREBBP GENE_PARTICIPATES_IN_PATHWAY TRAF6 mediated IRF7 activation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000059.4(BRCA2):c.4658del (p.Thr1553fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000059.4(BRCA2):c.4658del (p.Thr1553fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_000059.4(BRCA2):c.4658del (p.Thr1553fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CREBBP GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CREBBP GENE_PARTICIPATES_IN_PATHWAY TRAF6 mediated IRF7 activation | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA2",
"source_db": "UniProt",
"payload": {
"accession": "P51587",
"sequence": "MPIGSKERPTFFEIFKTRCNKADLGPISLNWFEELSSEAPPYNSEPAEESEHKNNNYEPNLFKTPQRKPSYNQLASTPIIFKEQGLTLPLYQSPVKELDKFKLDLGRNVPNSRHKSLRTVKTKMDQADDVSCP... | [
{
"source_db": "ClinVar",
"source_id": "BRCA2",
"text": "NM_000059.4(BRCA2):c.4658del (p.Thr1553fs) VARIANT_IN_GENE BRCA2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045893",
"text": "BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription... | {
"variant": "NM_000059.4(BRCA2):c.4658del (p.Thr1553fs)",
"pathway": "TRAF6 mediated IRF7 activation"
} | 0.774597 |
co_mech_00120 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_005228.5(EGFR):c.2239_2256delinsCAA (p.Leu747_Ser752delinsGln) affects the Defective pyroptosis pathway, citing each molecular step. | NM_005228.5(EGFR):c.2239_2256delinsCAA (p.Leu747_Ser752delinsGln) VARIANT_IN_GENE EGFR -> EGFR GENE_ANNOTATED_WITH_GO_TERM neuron differentiation -> DNMT3A GENE_ANNOTATED_WITH_GO_TERM neuron differentiation -> DNMT3A GENE_PARTICIPATES_IN_PATHWAY Defective pyroptosis | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_005228.5(EGFR):c.2239_2256delinsCAA (p.Leu747_Ser752delinsGln)",
"source_node_type": "VARIANT",
"source_node_label": "NM_005228.5(EGFR):c.2239_2256delinsCAA (p.Leu747_Ser752delinsGln)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evi... | NM_005228.5(EGFR):c.2239_2256delinsCAA (p.Leu747_Ser752delinsGln) VARIANT_IN_GENE EGFR -> EGFR GENE_ANNOTATED_WITH_GO_TERM neuron differentiation -> DNMT3A GENE_ANNOTATED_WITH_GO_TERM neuron differentiation -> DNMT3A GENE_PARTICIPATES_IN_PATHWAY Defective pyroptosis | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "EGFR",
"source_db": "UniProt",
"payload": {
"accession": "P00533",
"sequence": "MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKE... | [
{
"source_db": "ClinVar",
"source_id": "EGFR",
"text": "NM_005228.5(EGFR):c.2239_2256delinsCAA (p.Leu747_Ser752delinsGln) VARIANT_IN_GENE EGFR",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0030182",
"text": "EGFR GENE_ANNOTATED_WITH_GO_TERM neuron differentiation",
"... | {
"variant": "NM_005228.5(EGFR):c.2239_2256delinsCAA (p.Leu747_Ser752delinsGln)",
"pathway": "Defective pyroptosis"
} | 0.774597 |
co_mech_00121 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_001040108.2(MLH3):c.2116del (p.Thr706fs) affects the The NLRP1 inflammasome pathway, citing each molecular step. | NM_001040108.2(MLH3):c.2116del (p.Thr706fs) VARIANT_IN_GENE MLH3 -> MLH3 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MSH6 -> MSH6 GENE_ANNOTATED_WITH_GO_TERM intrinsic apoptotic signaling pathway in response to DNA damage -> BCL2 GENE_ANNOTATED_WITH_GO_TERM intrinsic apoptotic signaling pathway in response to DNA damage -> BC... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001040108.2(MLH3):c.2116del (p.Thr706fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001040108.2(MLH3):c.2116del (p.Thr706fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_001040108.2(MLH3):c.2116del (p.Thr706fs) VARIANT_IN_GENE MLH3 -> MLH3 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MSH6 -> MSH6 GENE_ANNOTATED_WITH_GO_TERM intrinsic apoptotic signaling pathway in response to DNA damage -> BCL2 GENE_ANNOTATED_WITH_GO_TERM intrinsic apoptotic signaling pathway in response to DNA damage -> BC... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MLH3",
"source_db": "UniProt",
"payload": {
"accession": "Q9UHC1",
"sequence": "MIKCLSVEVQAKLRSGLAISSLGQCVEELALNSIDAEAKCVAVRVNMETFQVQVIDNGFGMGSDDVEKVGNRYFTSKCHSVQDLENPRFYGFRGEALANIADMASAVEISSKKNRTMKTFVKLFQSGKALKACE... | [
{
"source_db": "ClinVar",
"source_id": "MLH3",
"text": "NM_001040108.2(MLH3):c.2116del (p.Thr706fs) VARIANT_IN_GENE MLH3",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "MSH6",
"text": "MLH3 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MSH6",
"confidence": 0.999
},
{
"... | {
"variant": "NM_001040108.2(MLH3):c.2116del (p.Thr706fs)",
"pathway": "The NLRP1 inflammasome"
} | 0.81503 |
co_mech_00122 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000249.4(MLH1):c.1664T>G (p.Leu555Arg) affects the Signaling by ERBB2 ECD mutants pathway, citing each molecular step. | NM_000249.4(MLH1):c.1664T>G (p.Leu555Arg) VARIANT_IN_GENE MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_PARTICIPATES_IN_PATHWAY Signaling by ERBB2 ECD mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000249.4(MLH1):c.1664T>G (p.Leu555Arg)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000249.4(MLH1):c.1664T>G (p.Leu555Arg)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000249.4(MLH1):c.1664T>G (p.Leu555Arg) VARIANT_IN_GENE MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_ANNOTATED_WITH_GO_TERM ATP binding -> EGFR GENE_PARTICIPATES_IN_PATHWAY Signaling by ERBB2 ECD mutants | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MLH1",
"source_db": "UniProt",
"payload": {
"accession": "P40692",
"sequence": "MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGK... | [
{
"source_db": "ClinVar",
"source_id": "MLH1",
"text": "NM_000249.4(MLH1):c.1664T>G (p.Leu555Arg) VARIANT_IN_GENE MLH1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"sour... | {
"variant": "NM_000249.4(MLH1):c.1664T>G (p.Leu555Arg)",
"pathway": "Signaling by ERBB2 ECD mutants"
} | 0.774597 |
co_mech_00123 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_003106.4(SOX2):c.59del (p.Gly20fs) affects the Negative Regulation of DNA Double Strand Break Response pathway, citing each molecular step. | NM_003106.4(SOX2):c.59del (p.Gly20fs) VARIANT_IN_GENE SOX2 -> SOX2 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Negative Regulation of DNA Double Strand Break Response | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_003106.4(SOX2):c.59del (p.Gly20fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_003106.4(SOX2):c.59del (p.Gly20fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_003106.4(SOX2):c.59del (p.Gly20fs) VARIANT_IN_GENE SOX2 -> SOX2 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Negative Regulation of DNA Double Strand Break Response | null | [
"conservation",
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_003106.4(SOX2):c.59del (p.Gly20fs)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr3",
"pos": 181712414,
"track": "phyloP100way",
"window": 20,
"scores": [
6.91583,
6.60... | [
{
"source_db": "ClinVar",
"source_id": "SOX2",
"text": "NM_003106.4(SOX2):c.59del (p.Gly20fs) VARIANT_IN_GENE SOX2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0000976",
"text": "SOX2 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding",
"confide... | {
"variant": "NM_003106.4(SOX2):c.59del (p.Gly20fs)",
"pathway": "Negative Regulation of DNA Double Strand Break Response"
} | 0.774597 |
co_mech_00124 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000546.6(TP53):c.1101-2_1101-1inv affects the RUNX1 regulates transcription of genes involved in differentiation of HSCs pathway, citing each molecular step. | NM_000546.6(TP53):c.1101-2_1101-1inv VARIANT_IN_GENE TP53 -> TP53 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH ATM -> ABL1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH ATM -> ABL1 GENE_PARTICIPATES_IN_PATHWAY RUNX1 regulates transcription of genes involved in differentiation of HSCs | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000546.6(TP53):c.1101-2_1101-1inv",
"source_node_type": "VARIANT",
"source_node_label": "NM_000546.6(TP53):c.1101-2_1101-1inv",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000546.6(TP53):c.1101-2_1101-1inv VARIANT_IN_GENE TP53 -> TP53 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH ATM -> ABL1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH ATM -> ABL1 GENE_PARTICIPATES_IN_PATHWAY RUNX1 regulates transcription of genes involved in differentiation of HSCs | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "TP53",
"source_db": "UniProt",
"payload": {
"accession": "P04637",
"sequence": "MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMF... | [
{
"source_db": "ClinVar",
"source_id": "TP53",
"text": "NM_000546.6(TP53):c.1101-2_1101-1inv VARIANT_IN_GENE TP53",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "ATM",
"text": "TP53 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH ATM",
"confidence": 0.999
},
{
"source_db... | {
"variant": "NM_000546.6(TP53):c.1101-2_1101-1inv",
"pathway": "RUNX1 regulates transcription of genes involved in differentiation of HSCs"
} | 0.996737 |
co_mech_00125 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000179.3(MSH6):c.3863_3864del (p.Lys1288fs) affects the Oncogene Induced Senescence pathway, citing each molecular step. | NM_000179.3(MSH6):c.3863_3864del (p.Lys1288fs) VARIANT_IN_GENE MSH6 -> MSH6 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY Oncogene Induced Senescence | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000179.3(MSH6):c.3863_3864del (p.Lys1288fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000179.3(MSH6):c.3863_3864del (p.Lys1288fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_co... | NM_000179.3(MSH6):c.3863_3864del (p.Lys1288fs) VARIANT_IN_GENE MSH6 -> MSH6 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY Oncogene Induced Senescence | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH6",
"source_db": "UniProt",
"payload": {
"accession": "P52701",
"sequence": "MSRQSTLYSFFPKSPALSDANKASARASREGGRAAAAPGASPSPGGDAAWSEAGPGPRPLARSASPPKAKNLNGGLRRSVAPAAPTSCDFSPGDLVWAKMEGYPWWPCLVYNHPFDGTFIREKGKSVRVHVQFF... | [
{
"source_db": "ClinVar",
"source_id": "MSH6",
"text": "NM_000179.3(MSH6):c.3863_3864del (p.Lys1288fs) VARIANT_IN_GENE MSH6",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA1",
"text": "MSH6 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1",
"confidence": 0.996
},
{
... | {
"variant": "NM_000179.3(MSH6):c.3863_3864del (p.Lys1288fs)",
"pathway": "Oncogene Induced Senescence"
} | 0.998749 |
co_mech_00126 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_007294.4(BRCA1):c.3255del (p.Arg1085fs) affects the Degradation of AXIN pathway, citing each molecular step. | NM_007294.4(BRCA1):c.3255del (p.Arg1085fs) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> AXIN2 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> AXIN2 GENE_PARTICIPATES_IN_PATHWAY Degradation of AXIN | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007294.4(BRCA1):c.3255del (p.Arg1085fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007294.4(BRCA1):c.3255del (p.Arg1085fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_007294.4(BRCA1):c.3255del (p.Arg1085fs) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> AXIN2 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> AXIN2 GENE_PARTICIPATES_IN_PATHWAY Degradation of AXIN | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA1",
"source_db": "UniProt",
"payload": {
"accession": "P38398",
"sequence": "MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNR... | [
{
"source_db": "ClinVar",
"source_id": "BRCA1",
"text": "NM_007294.4(BRCA1):c.3255del (p.Arg1085fs) VARIANT_IN_GENE BRCA1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0031625",
"text": "BRCA1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding",
"confidence... | {
"variant": "NM_007294.4(BRCA1):c.3255del (p.Arg1085fs)",
"pathway": "Degradation of AXIN"
} | 0.774597 |
co_mech_00127 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_015338.6(ASXL1):c.4196dup (p.Leu1399fs) affects the Formation of the canonical BAF (cBAF) complex pathway, citing each molecular step. | NM_015338.6(ASXL1):c.4196dup (p.Leu1399fs) VARIANT_IN_GENE ASXL1 -> ASXL1 GENE_PARTICIPATES_IN_PATHWAY UCH proteinases -> ACTB GENE_PARTICIPATES_IN_PATHWAY UCH proteinases -> ACTB GENE_PARTICIPATES_IN_PATHWAY Formation of the canonical BAF (cBAF) complex | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_015338.6(ASXL1):c.4196dup (p.Leu1399fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_015338.6(ASXL1):c.4196dup (p.Leu1399fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_015338.6(ASXL1):c.4196dup (p.Leu1399fs) VARIANT_IN_GENE ASXL1 -> ASXL1 GENE_PARTICIPATES_IN_PATHWAY UCH proteinases -> ACTB GENE_PARTICIPATES_IN_PATHWAY UCH proteinases -> ACTB GENE_PARTICIPATES_IN_PATHWAY Formation of the canonical BAF (cBAF) complex | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ASXL1",
"source_db": "UniProt",
"payload": {
"accession": "Q8IXJ9",
"sequence": "MKDKQKKKKERTWAEAARLVLENYSDAPMTPKQILQVIEAEGLKEMRSGTSPLACLNAMLHSNSRGGEGLFYKLPGRISLFTLKKDALQWSRHPATVEGEEPEDTADVESCGSNEASTVSGENDVSLDETSSN... | [
{
"source_db": "ClinVar",
"source_id": "ASXL1",
"text": "NM_015338.6(ASXL1):c.4196dup (p.Leu1399fs) VARIANT_IN_GENE ASXL1",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-5689603",
"text": "ASXL1 GENE_PARTICIPATES_IN_PATHWAY UCH proteinases",
"confidence": 1
... | {
"variant": "NM_015338.6(ASXL1):c.4196dup (p.Leu1399fs)",
"pathway": "Formation of the canonical BAF (cBAF) complex"
} | 1 |
co_mech_00128 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000267.3:c.2964_2965insALU affects the sorafenib-resistant FLT3 mutants pathway, citing each molecular step. | NM_000267.3:c.2964_2965insALU VARIANT_IN_GENE NF1 -> NF1 GENE_ANNOTATED_WITH_GO_TERM liver development -> CEBPA GENE_ANNOTATED_WITH_GO_TERM liver development -> CEBPA PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FLT3 -> FLT3 GENE_PARTICIPATES_IN_PATHWAY sorafenib-resistant FLT3 mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000267.3:c.2964_2965insALU",
"source_node_type": "VARIANT",
"source_node_label": "NM_000267.3:c.2964_2965insALU",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_d... | NM_000267.3:c.2964_2965insALU VARIANT_IN_GENE NF1 -> NF1 GENE_ANNOTATED_WITH_GO_TERM liver development -> CEBPA GENE_ANNOTATED_WITH_GO_TERM liver development -> CEBPA PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FLT3 -> FLT3 GENE_PARTICIPATES_IN_PATHWAY sorafenib-resistant FLT3 mutants | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "NF1",
"source_db": "UniProt",
"payload": {
"accession": "P21359",
"sequence": "MAAHRPVEWVQAVVSRFDEQLPIKTGQQNTHTKVSTEHNKECLINISKYKFSLVISGLTTILKNVNNMRIFGEAAEKNLYLSQLIILDTLEKCLAGQPKDTMRLDETMLVKQLLPEICHFLHTCREGNQHAAELR... | [
{
"source_db": "ClinVar",
"source_id": "NF1",
"text": "NM_000267.3:c.2964_2965insALU VARIANT_IN_GENE NF1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0001889",
"text": "NF1 GENE_ANNOTATED_WITH_GO_TERM liver development",
"confidence": 0.6
},
{
"source_db": "... | {
"variant": "NM_000267.3:c.2964_2965insALU",
"pathway": "sorafenib-resistant FLT3 mutants"
} | 0.812072 |
co_mech_00129 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000051.4(ATM):c.2125-16_2128delinsCAAATTTATATT affects the Serotonin Neurotransmitter Release Cycle pathway, citing each molecular step. | NM_000051.4(ATM):c.2125-16_2128delinsCAAATTTATATT VARIANT_IN_GENE ATM -> ATM GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> SNCA GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> SLC18A2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH SNCA -> SLC18A2 GENE_PARTICIPATES_IN_PATHWAY Sero... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000051.4(ATM):c.2125-16_2128delinsCAAATTTATATT",
"source_node_type": "VARIANT",
"source_node_label": "NM_000051.4(ATM):c.2125-16_2128delinsCAAATTTATATT",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"e... | NM_000051.4(ATM):c.2125-16_2128delinsCAAATTTATATT VARIANT_IN_GENE ATM -> ATM GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> SNCA GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> SLC18A2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH SNCA -> SLC18A2 GENE_PARTICIPATES_IN_PATHWAY Sero... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ATM",
"source_db": "UniProt",
"payload": {
"accession": "Q13315",
"sequence": "MSLVLNDLLICCRQLEHDRATERKKEVEKFKRLIRDPETIKHLDRHSDSKQGKYLNWDAVFRFLQKYIQKETECLRIAKPNVSASTQASRQKKMQEISSLVKYFIKCANRRAPRLKCQELLNYIMDTVKDSSNGA... | [
{
"source_db": "ClinVar",
"source_id": "ATM",
"text": "NM_000051.4(ATM):c.2125-16_2128delinsCAAATTTATATT VARIANT_IN_GENE ATM",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0043065",
"text": "ATM GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process",
"c... | {
"variant": "NM_000051.4(ATM):c.2125-16_2128delinsCAAATTTATATT",
"pathway": "Serotonin Neurotransmitter Release Cycle"
} | 0.81174 |
co_mech_00130 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_000021.4(PSEN1):c.505T>C (p.Ser169Pro) affects the Cardiogenesis pathway, citing each molecular step. | NM_000021.4(PSEN1):c.505T>C (p.Ser169Pro) VARIANT_IN_GENE PSEN1 -> PSEN1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Cardiogenesis | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000021.4(PSEN1):c.505T>C (p.Ser169Pro)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000021.4(PSEN1):c.505T>C (p.Ser169Pro)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000021.4(PSEN1):c.505T>C (p.Ser169Pro) VARIANT_IN_GENE PSEN1 -> PSEN1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Cardiogenesis | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PSEN1",
"source_db": "UniProt",
"payload": {
"accession": "P49768",
"sequence": "MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSRQVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVGQRALHSI... | [
{
"source_db": "ClinVar",
"source_id": "PSEN1",
"text": "NM_000021.4(PSEN1):c.505T>C (p.Ser169Pro) VARIANT_IN_GENE PSEN1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "CTNNB1",
"text": "PSEN1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1",
"confidence": 0.999
},
{
... | {
"variant": "NM_000021.4(PSEN1):c.505T>C (p.Ser169Pro)",
"pathway": "Cardiogenesis"
} | 0.999667 |
co_mech_00131 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000059.4(BRCA2):c.9629_9630dup (p.Thr3211fs) affects the PCNA-Dependent Long Patch Base Excision Repair pathway, citing each molecular step. | NM_000059.4(BRCA2):c.9629_9630dup (p.Thr3211fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_PARTICIPATES_IN_PATHWAY HDR through Homologous Recombination (HRR) -> POLD1 GENE_PARTICIPATES_IN_PATHWAY HDR through Homologous Recombination (HRR) -> POLD1 GENE_PARTICIPATES_IN_PATHWAY PCNA-Dependent Long Patch Base Excision Repair | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000059.4(BRCA2):c.9629_9630dup (p.Thr3211fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000059.4(BRCA2):c.9629_9630dup (p.Thr3211fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_... | NM_000059.4(BRCA2):c.9629_9630dup (p.Thr3211fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_PARTICIPATES_IN_PATHWAY HDR through Homologous Recombination (HRR) -> POLD1 GENE_PARTICIPATES_IN_PATHWAY HDR through Homologous Recombination (HRR) -> POLD1 GENE_PARTICIPATES_IN_PATHWAY PCNA-Dependent Long Patch Base Excision Repair | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA2",
"source_db": "UniProt",
"payload": {
"accession": "P51587",
"sequence": "MPIGSKERPTFFEIFKTRCNKADLGPISLNWFEELSSEAPPYNSEPAEESEHKNNNYEPNLFKTPQRKPSYNQLASTPIIFKEQGLTLPLYQSPVKELDKFKLDLGRNVPNSRHKSLRTVKTKMDQADDVSCP... | [
{
"source_db": "ClinVar",
"source_id": "BRCA2",
"text": "NM_000059.4(BRCA2):c.9629_9630dup (p.Thr3211fs) VARIANT_IN_GENE BRCA2",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-5685942",
"text": "BRCA2 GENE_PARTICIPATES_IN_PATHWAY HDR through Homologous Recombinatio... | {
"variant": "NM_000059.4(BRCA2):c.9629_9630dup (p.Thr3211fs)",
"pathway": "PCNA-Dependent Long Patch Base Excision Repair"
} | 1 |
co_mech_00132 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_032043.3(BRIP1):c.2257+2_2257+8del affects the UCH proteinases pathway, citing each molecular step. | NM_032043.3(BRIP1):c.2257+2_2257+8del VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BARD1 -> BARD1 GENE_PARTICIPATES_IN_PATHWAY UCH proteinases | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_032043.3(BRIP1):c.2257+2_2257+8del",
"source_node_type": "VARIANT",
"source_node_label": "NM_032043.3(BRIP1):c.2257+2_2257+8del",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_032043.3(BRIP1):c.2257+2_2257+8del VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BARD1 -> BARD1 GENE_PARTICIPATES_IN_PATHWAY UCH proteinases | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRIP1",
"source_db": "UniProt",
"payload": {
"accession": "Q9BX63",
"sequence": "MSSMWSEYTIGGVKIYFPYKAYPSQLAMMNSILRGLNSKQHCLLESPTGSGKSLALLCSALAWQQSLSGKPADEGVSEKAEVQLSCCCACHSKDFTNNDMNQGTSRHFNYPSTPPSERNGTSSTCQDSPEKTT... | [
{
"source_db": "ClinVar",
"source_id": "BRIP1",
"text": "NM_032043.3(BRIP1):c.2257+2_2257+8del VARIANT_IN_GENE BRIP1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BARD1",
"text": "BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BARD1",
"confidence": 0.999
},
{
"s... | {
"variant": "NM_032043.3(BRIP1):c.2257+2_2257+8del",
"pathway": "UCH proteinases"
} | 0.999667 |
co_mech_00133 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_001042492.3(NF1):c.1395del (p.Thr467fs) affects the CD209 (DC-SIGN) signaling pathway, citing each molecular step. | NM_001042492.3(NF1):c.1395del (p.Thr467fs) VARIANT_IN_GENE NF1 -> NF1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY CD209 (DC-SIGN) signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001042492.3(NF1):c.1395del (p.Thr467fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001042492.3(NF1):c.1395del (p.Thr467fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_001042492.3(NF1):c.1395del (p.Thr467fs) VARIANT_IN_GENE NF1 -> NF1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY CD209 (DC-SIGN) signaling | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "NF1",
"source_db": "UniProt",
"payload": {
"accession": "P21359",
"sequence": "MAAHRPVEWVQAVVSRFDEQLPIKTGQQNTHTKVSTEHNKECLINISKYKFSLVISGLTTILKNVNNMRIFGEAAEKNLYLSQLIILDTLEKCLAGQPKDTMRLDETMLVKQLLPEICHFLHTCREGNQHAAELR... | [
{
"source_db": "ClinVar",
"source_id": "NF1",
"text": "NM_001042492.3(NF1):c.1395del (p.Thr467fs) VARIANT_IN_GENE NF1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "NRAS",
"text": "NF1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS",
"confidence": 0.994
},
{
"sour... | {
"variant": "NM_001042492.3(NF1):c.1395del (p.Thr467fs)",
"pathway": "CD209 (DC-SIGN) signaling"
} | 0.997996 |
co_mech_00134 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000455.5(STK11):c.634_652del (p.Thr212fs) affects the Cyclin A:Cdk2-associated events at S phase entry pathway, citing each molecular step. | NM_000455.5(STK11):c.634_652del (p.Thr212fs) VARIANT_IN_GENE STK11 -> STK11 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT1 GENE_PARTICIPATES_IN_PATHWAY Cyclin A:Cdk2-associated events at S phase entry | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000455.5(STK11):c.634_652del (p.Thr212fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000455.5(STK11):c.634_652del (p.Thr212fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_000455.5(STK11):c.634_652del (p.Thr212fs) VARIANT_IN_GENE STK11 -> STK11 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT1 GENE_PARTICIPATES_IN_PATHWAY Cyclin A:Cdk2-associated events at S phase entry | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "STK11",
"source_db": "UniProt",
"payload": {
"accession": "Q15831",
"sequence": "MEVVDPQQLGMFTEGELMSVGMDTFIHRIDSTEVIYQPRRKRAKLIGKYLMGDLLGEGSYGKVKEVLDSETLCRRAVKILKKKKLRRIPNGEANVKKEIQLLRRLRHKNVIQLVDVLYNEEKQKMYMVMEYCV... | [
{
"source_db": "ClinVar",
"source_id": "STK11",
"text": "NM_000455.5(STK11):c.634_652del (p.Thr212fs) VARIANT_IN_GENE STK11",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "STK11 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
... | {
"variant": "NM_000455.5(STK11):c.634_652del (p.Thr212fs)",
"pathway": "Cyclin A:Cdk2-associated events at S phase entry"
} | 0.774597 |
co_mech_00135 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000245.4(MET):c.3281A>G (p.His1094Arg) affects the Regulation of ornithine decarboxylase (ODC) pathway, citing each molecular step. | NM_000245.4(MET):c.3281A>G (p.His1094Arg) VARIANT_IN_GENE MET -> MET PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CBL -> CBL GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY Regulation of ornithine decarboxylase (ODC) | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000245.4(MET):c.3281A>G (p.His1094Arg)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000245.4(MET):c.3281A>G (p.His1094Arg)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000245.4(MET):c.3281A>G (p.His1094Arg) VARIANT_IN_GENE MET -> MET PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CBL -> CBL GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY Regulation of ornithine decarboxylase (ODC) | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_000245.4(MET):c.3281A>G (p.His1094Arg)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr7",
"pos": 116777410,
"track": "phyloP100way",
"window": 20,
"scores": [
-0.085126,
... | [
{
"source_db": "ClinVar",
"source_id": "MET",
"text": "NM_000245.4(MET):c.3281A>G (p.His1094Arg) VARIANT_IN_GENE MET",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "CBL",
"text": "MET PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CBL",
"confidence": 0.999
},
{
"source_... | {
"variant": "NM_000245.4(MET):c.3281A>G (p.His1094Arg)",
"pathway": "Regulation of ornithine decarboxylase (ODC)"
} | 0.81503 |
co_mech_00136 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000051.3:c.3862_3863insALU affects the LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production pathway, citing each molecular step. | NM_000051.3:c.3862_3863insALU VARIANT_IN_GENE ATM -> ATM GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> CTNNB1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000051.3:c.3862_3863insALU",
"source_node_type": "VARIANT",
"source_node_label": "NM_000051.3:c.3862_3863insALU",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_d... | NM_000051.3:c.3862_3863insALU VARIANT_IN_GENE ATM -> ATM GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> CTNNB1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ATM",
"source_db": "UniProt",
"payload": {
"accession": "Q13315",
"sequence": "MSLVLNDLLICCRQLEHDRATERKKEVEKFKRLIRDPETIKHLDRHSDSKQGKYLNWDAVFRFLQKYIQKETECLRIAKPNVSASTQASRQKKMQEISSLVKYFIKCANRRAPRLKCQELLNYIMDTVKDSSNGA... | [
{
"source_db": "ClinVar",
"source_id": "ATM",
"text": "NM_000051.3:c.3862_3863insALU VARIANT_IN_GENE ATM",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0043065",
"text": "ATM GENE_ANNOTATED_WITH_GO_TERM positive regulation of apoptotic process",
"confidence": 0.6
},... | {
"variant": "NM_000051.3:c.3862_3863insALU",
"pathway": "LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production"
} | 0.774597 |
co_mech_00137 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000249.4(MLH1):c.1771del (p.Asp591fs) affects the ER-Phagosome pathway pathway, citing each molecular step. | NM_000249.4(MLH1):c.1771del (p.Asp591fs) VARIANT_IN_GENE MLH1 -> MLH1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BLM -> BLM GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY ER-Phagosome pathway | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000249.4(MLH1):c.1771del (p.Asp591fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000249.4(MLH1):c.1771del (p.Asp591fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_000249.4(MLH1):c.1771del (p.Asp591fs) VARIANT_IN_GENE MLH1 -> MLH1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BLM -> BLM GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY ER-Phagosome pathway | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MLH1",
"source_db": "UniProt",
"payload": {
"accession": "P40692",
"sequence": "MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGK... | [
{
"source_db": "ClinVar",
"source_id": "MLH1",
"text": "NM_000249.4(MLH1):c.1771del (p.Asp591fs) VARIANT_IN_GENE MLH1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BLM",
"text": "MLH1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BLM",
"confidence": 0.999
},
{
"sourc... | {
"variant": "NM_000249.4(MLH1):c.1771del (p.Asp591fs)",
"pathway": "ER-Phagosome pathway"
} | 0.81503 |
co_mech_00138 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000038.6(APC):c.531+5_531+8del affects the Signaling by MAP2K mutants pathway, citing each molecular step. | NM_000038.6(APC):c.531+5_531+8del VARIANT_IN_GENE APC -> APC GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> MAPK1 GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> MAPK1 GENE_PARTICIPATES_IN_PATHWAY Signaling by MAP2K mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000038.6(APC):c.531+5_531+8del",
"source_node_type": "VARIANT",
"source_node_label": "NM_000038.6(APC):c.531+5_531+8del",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_... | NM_000038.6(APC):c.531+5_531+8del VARIANT_IN_GENE APC -> APC GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> MAPK1 GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway -> MAPK1 GENE_PARTICIPATES_IN_PATHWAY Signaling by MAP2K mutants | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "APC",
"source_db": "UniProt",
"payload": {
"accession": "P25054",
"sequence": "MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTKLETEASNMKEVLKQLQGSIEDEAMASSGQIDLLERLKELNLDSSNFPGVKLRSKMSLRSYGSREGSVSSRSGECSPVPMGSFPRRGFVNGSRESTGYLE... | [
{
"source_db": "ClinVar",
"source_id": "APC",
"text": "NM_000038.6(APC):c.531+5_531+8del VARIANT_IN_GENE APC",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008286",
"text": "APC GENE_ANNOTATED_WITH_GO_TERM insulin receptor signaling pathway",
"confidence": 0.6
},
... | {
"variant": "NM_000038.6(APC):c.531+5_531+8del",
"pathway": "Signaling by MAP2K mutants"
} | 0.774597 |
co_mech_00139 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000057.4(BLM):c.3504dup (p.Ala1169fs) affects the SOS-mediated signalling pathway, citing each molecular step. | NM_000057.4(BLM):c.3504dup (p.Ala1169fs) VARIANT_IN_GENE BLM -> BLM GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ALK GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ALK PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY SOS-mediated signalling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000057.4(BLM):c.3504dup (p.Ala1169fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000057.4(BLM):c.3504dup (p.Ala1169fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_000057.4(BLM):c.3504dup (p.Ala1169fs) VARIANT_IN_GENE BLM -> BLM GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ALK GENE_ANNOTATED_WITH_GO_TERM ATP binding -> ALK PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY SOS-mediated signalling | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BLM",
"source_db": "UniProt",
"payload": {
"accession": "P54132",
"sequence": "MAAVPQNNLQEQLERHSARTLNNKLSLSKPKFSGFTFKKKTSSDNNVSVTNVSVAKTPVLRNKDVNVTEDFSFSEPLPNTTNQQRVKDFFKNAPAGQETQRGGSKSLLPDFLQTPKEVVCTTQNTPTVKKSRDTA... | [
{
"source_db": "ClinVar",
"source_id": "BLM",
"text": "NM_000057.4(BLM):c.3504dup (p.Ala1169fs) VARIANT_IN_GENE BLM",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "BLM GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"source_d... | {
"variant": "NM_000057.4(BLM):c.3504dup (p.Ala1169fs)",
"pathway": "SOS-mediated signalling"
} | 0.812898 |
co_mech_00140 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000057.4(BLM):c.1220+1G>T affects the Voltage gated Potassium channels pathway, citing each molecular step. | NM_000057.4(BLM):c.1220+1G>T VARIANT_IN_GENE BLM -> BLM GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> AR GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> ERG PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH AR -> ERG GENE_PARTICIPATES_IN_PATHWAY Voltage gated Potassium channels | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000057.4(BLM):c.1220+1G>T",
"source_node_type": "VARIANT",
"source_node_label": "NM_000057.4(BLM):c.1220+1G>T",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_db"... | NM_000057.4(BLM):c.1220+1G>T VARIANT_IN_GENE BLM -> BLM GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> AR GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> ERG PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH AR -> ERG GENE_PARTICIPATES_IN_PATHWAY Voltage gated Potassium channels | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BLM",
"source_db": "UniProt",
"payload": {
"accession": "P54132",
"sequence": "MAAVPQNNLQEQLERHSARTLNNKLSLSKPKFSGFTFKKKTSSDNNVSVTNVSVAKTPVLRNKDVNVTEDFSFSEPLPNTTNQQRVKDFFKNAPAGQETQRGGSKSLLPDFLQTPKEVVCTTQNTPTVKKSRDTA... | [
{
"source_db": "ClinVar",
"source_id": "BLM",
"text": "NM_000057.4(BLM):c.1220+1G>T VARIANT_IN_GENE BLM",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008270",
"text": "BLM GENE_ANNOTATED_WITH_GO_TERM zinc ion binding",
"confidence": 0.6
},
{
"source_db": "GO... | {
"variant": "NM_000057.4(BLM):c.1220+1G>T",
"pathway": "Voltage gated Potassium channels"
} | 0.796949 |
co_mech_00141 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000041.3(APOE):c.[784G>A;787G>A] affects the MAPK3 (ERK1) activation pathway, citing each molecular step. | NM_000041.3(APOE):c.[784G>A;787G>A] VARIANT_IN_GENE APOE -> APOE GENE_ANNOTATED_WITH_GO_TERM positive regulation of nitric oxide biosynthetic process -> JAK2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of nitric oxide biosynthetic process -> JAK2 GENE_PARTICIPATES_IN_PATHWAY MAPK3 (ERK1) activation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000041.4(APOE):c.784G>A (p.Glu262Lys)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000041.3(APOE):c.[784G>A;787G>A]",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000041.3(APOE):c.[784G>A;787G>A] VARIANT_IN_GENE APOE -> APOE GENE_ANNOTATED_WITH_GO_TERM positive regulation of nitric oxide biosynthetic process -> JAK2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of nitric oxide biosynthetic process -> JAK2 GENE_PARTICIPATES_IN_PATHWAY MAPK3 (ERK1) activation | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "APOE",
"source_db": "UniProt",
"payload": {
"accession": "P02649",
"sequence": "MKVLWAALLVTFLAGCQAKVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVCGRLV... | [
{
"source_db": "ClinVar",
"source_id": "APOE",
"text": "NM_000041.3(APOE):c.[784G>A;787G>A] VARIANT_IN_GENE APOE",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045429",
"text": "APOE GENE_ANNOTATED_WITH_GO_TERM positive regulation of nitric oxide biosynthetic process",
... | {
"variant": "NM_000041.3(APOE):c.[784G>A;787G>A]",
"pathway": "MAPK3 (ERK1) activation"
} | 0.774597 |
co_mech_00142 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_001386135.1(AFF3):c.697G>A (p.Ala233Thr) affects the Signaling by high-kinase activity BRAF mutants pathway, citing each molecular step. | NM_001386135.1(AFF3):c.697G>A (p.Ala233Thr) VARIANT_IN_GENE AFF3 -> AFF3 GENE_PARTICIPATES_IN_PATHWAY Signaling by FGFR2 in disease -> NRAS GENE_PARTICIPATES_IN_PATHWAY Signaling by FGFR2 in disease -> NRAS GENE_PARTICIPATES_IN_PATHWAY Signaling by high-kinase activity BRAF mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001386135.1(AFF3):c.697G>A (p.Ala233Thr)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001386135.1(AFF3):c.697G>A (p.Ala233Thr)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_001386135.1(AFF3):c.697G>A (p.Ala233Thr) VARIANT_IN_GENE AFF3 -> AFF3 GENE_PARTICIPATES_IN_PATHWAY Signaling by FGFR2 in disease -> NRAS GENE_PARTICIPATES_IN_PATHWAY Signaling by FGFR2 in disease -> NRAS GENE_PARTICIPATES_IN_PATHWAY Signaling by high-kinase activity BRAF mutants | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_001386135.1(AFF3):c.697G>A (p.Ala233Thr)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr2",
"pos": 100006808,
"track": "phyloP100way",
"window": 20,
"scores": [
-1.56789,
... | [
{
"source_db": "ClinVar",
"source_id": "AFF3",
"text": "NM_001386135.1(AFF3):c.697G>A (p.Ala233Thr) VARIANT_IN_GENE AFF3",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-5655253",
"text": "AFF3 GENE_PARTICIPATES_IN_PATHWAY Signaling by FGFR2 in disease",
"confi... | {
"variant": "NM_001386135.1(AFF3):c.697G>A (p.Ala233Thr)",
"pathway": "Signaling by high-kinase activity BRAF mutants"
} | 1 |
co_mech_00143 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_007294.4(BRCA1):c.131_132delinsCT (p.Cys44Ser) affects the Role of LAT2/NTAL/LAB on calcium mobilization pathway, citing each molecular step. | NM_007294.4(BRCA1):c.131_132delinsCT (p.Cys44Ser) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> EGFR GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> EGFR PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PIK3CA -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Role of LAT2/NTAL/... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007294.4(BRCA1):c.131_132delinsCT (p.Cys44Ser)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007294.4(BRCA1):c.131_132delinsCT (p.Cys44Ser)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"e... | NM_007294.4(BRCA1):c.131_132delinsCT (p.Cys44Ser) VARIANT_IN_GENE BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> EGFR GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> EGFR PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PIK3CA -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Role of LAT2/NTAL/... | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA1",
"source_db": "UniProt",
"payload": {
"accession": "P38398",
"sequence": "MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNR... | [
{
"source_db": "ClinVar",
"source_id": "BRCA1",
"text": "NM_007294.4(BRCA1):c.131_132delinsCT (p.Cys44Ser) VARIANT_IN_GENE BRCA1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0031625",
"text": "BRCA1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding",
"con... | {
"variant": "NM_007294.4(BRCA1):c.131_132delinsCT (p.Cys44Ser)",
"pathway": "Role of LAT2/NTAL/LAB on calcium mobilization"
} | 0.81503 |
co_mech_00144 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NC_000011.10:g.(108286180_108289631)del affects the RUNX1 regulates estrogen receptor mediated transcription pathway, citing each molecular step. | NC_000011.10:g.(108286180_108289631)del VARIANT_IN_GENE ATM -> ATM PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> ESR1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> ESR1 GENE_PARTICIPATES_IN_PATHWAY RUNX1 regulates estrogen receptor mediated transcription | {
"steps": [
{
"hop": 1,
"source_node_id": "NC_000011.10:g.(108286180_108289631)del",
"source_node_type": "VARIANT",
"source_node_label": "NC_000011.10:g.(108286180_108289631)del",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NC_000011.10:g.(108286180_108289631)del VARIANT_IN_GENE ATM -> ATM PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> ESR1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> ESR1 GENE_PARTICIPATES_IN_PATHWAY RUNX1 regulates estrogen receptor mediated transcription | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ATM",
"source_db": "UniProt",
"payload": {
"accession": "Q13315",
"sequence": "MSLVLNDLLICCRQLEHDRATERKKEVEKFKRLIRDPETIKHLDRHSDSKQGKYLNWDAVFRFLQKYIQKETECLRIAKPNVSASTQASRQKKMQEISSLVKYFIKCANRRAPRLKCQELLNYIMDTVKDSSNGA... | [
{
"source_db": "ClinVar",
"source_id": "ATM",
"text": "NC_000011.10:g.(108286180_108289631)del VARIANT_IN_GENE ATM",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA1",
"text": "ATM PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1",
"confidence": 0.999
},
{
"sourc... | {
"variant": "NC_000011.10:g.(108286180_108289631)del",
"pathway": "RUNX1 regulates estrogen receptor mediated transcription"
} | 0.9995 |
co_mech_00145 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000535.7(PMS2):c.706-1G>A affects the Association of TriC/CCT with target proteins during biosynthesis pathway, citing each molecular step. | NM_000535.7(PMS2):c.706-1G>A VARIANT_IN_GENE PMS2 -> PMS2 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> TP53 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> TP53 GENE_PARTICIPATES_IN_PATHWAY Association of TriC/CCT with target proteins during biosynthe... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000535.7(PMS2):c.706-1G>A",
"source_node_type": "VARIANT",
"source_node_label": "NM_000535.7(PMS2):c.706-1G>A",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_db"... | NM_000535.7(PMS2):c.706-1G>A VARIANT_IN_GENE PMS2 -> PMS2 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> TP53 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> TP53 GENE_PARTICIPATES_IN_PATHWAY Association of TriC/CCT with target proteins during biosynthe... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PMS2",
"source_db": "UniProt",
"payload": {
"accession": "P54278",
"sequence": "MERAESSSTEPAKAIKPIDRKSVHQICSGQVVLSLSTAVKELVENSLDAGATNIDLKLKDYGVDLIEVSDNGCGVEEENFEGLTLKHHTSKIQEFADLTQVETFGFRGEALSSLCALSDVTISTCHASAKVGTR... | [
{
"source_db": "ClinVar",
"source_id": "PMS2",
"text": "NM_000535.7(PMS2):c.706-1G>A VARIANT_IN_GENE PMS2",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-6796648",
"text": "PMS2 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes",
"c... | {
"variant": "NM_000535.7(PMS2):c.706-1G>A",
"pathway": "Association of TriC/CCT with target proteins during biosynthesis"
} | 1 |
co_mech_00146 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which GRCh37/hg19 2q35(chr2:215632206-215634036)x1 affects the NOTCH3 Intracellular Domain Regulates Transcription pathway, citing each molecular step. | GRCh37/hg19 2q35(chr2:215632206-215634036)x1 VARIANT_IN_GENE BARD1 -> BARD1 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CREBBP GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CREBBP GENE_PARTICIPATES_IN_PATHWAY NOTCH3 Intracellular Domain Regulates Transcription | {
"steps": [
{
"hop": 1,
"source_node_id": "GRCh37/hg19 2q35(chr2:215632206-215634036)x1",
"source_node_type": "VARIANT",
"source_node_label": "GRCh37/hg19 2q35(chr2:215632206-215634036)x1",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | GRCh37/hg19 2q35(chr2:215632206-215634036)x1 VARIANT_IN_GENE BARD1 -> BARD1 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CREBBP GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CREBBP GENE_PARTICIPATES_IN_PATHWAY NOTCH3 Intracellular Domain Regulates Transcription | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BARD1",
"source_db": "UniProt",
"payload": {
"accession": "Q99728",
"sequence": "MPDNRQPRNRQPRIRSGNEPRSAPAMEPDGRGAWAHSRAALDRLEKLLRCSRCTNILREPVCLGGCEHIFCSNCVSDCIGTGCPVCYTPAWIQDLKINRQLDSMIQLCSKLRNLLHDNELSDLKEDKPRKSLF... | [
{
"source_db": "ClinVar",
"source_id": "BARD1",
"text": "GRCh37/hg19 2q35(chr2:215632206-215634036)x1 VARIANT_IN_GENE BARD1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008270",
"text": "BARD1 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding",
"confidence": 0.6
},
... | {
"variant": "GRCh37/hg19 2q35(chr2:215632206-215634036)x1",
"pathway": "NOTCH3 Intracellular Domain Regulates Transcription"
} | 0.774597 |
co_mech_00147 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_024675.4(PALB2):c.133_139del (p.Lys45fs) affects the Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) pathway, citing each molecular step. | NM_024675.4(PALB2):c.133_139del (p.Lys45fs) VARIANT_IN_GENE PALB2 -> PALB2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> CTNNB1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Synthesis, secretion, ... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_024675.4(PALB2):c.133_139del (p.Lys45fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_024675.4(PALB2):c.133_139del (p.Lys45fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_024675.4(PALB2):c.133_139del (p.Lys45fs) VARIANT_IN_GENE PALB2 -> PALB2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1 -> BRCA1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> CTNNB1 GENE_ANNOTATED_WITH_GO_TERM ubiquitin protein ligase binding -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Synthesis, secretion, ... | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PALB2",
"source_db": "UniProt",
"payload": {
"accession": "Q86YC2",
"sequence": "MDEPPGKPLSCEEKEKLKEKLAFLKREYSKTLARLQRAQRAEKIKHSIKKTVEEQDCLSQQDLSPQLKHSEPKNKICVYDKLHIKTHLDEETGEKTSITLDVGPESFNPGDGPGGLPIQRTDDTQEHFPHRVS... | [
{
"source_db": "ClinVar",
"source_id": "PALB2",
"text": "NM_024675.4(PALB2):c.133_139del (p.Lys45fs) VARIANT_IN_GENE PALB2",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA1",
"text": "PALB2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA1",
"confidence": 0.999
},
{
... | {
"variant": "NM_024675.4(PALB2):c.133_139del (p.Lys45fs)",
"pathway": "Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)"
} | 0.81503 |
co_mech_00148 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_001040108.2(MLH3):c.980dup (p.Ile328fs) affects the Metalloprotease DUBs pathway, citing each molecular step. | NM_001040108.2(MLH3):c.980dup (p.Ile328fs) VARIANT_IN_GENE MLH3 -> MLH3 GENE_PARTICIPATES_IN_PATHWAY Meiotic recombination -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Meiotic recombination -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Metalloprotease DUBs | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001040108.2(MLH3):c.980dup (p.Ile328fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001040108.2(MLH3):c.980dup (p.Ile328fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_001040108.2(MLH3):c.980dup (p.Ile328fs) VARIANT_IN_GENE MLH3 -> MLH3 GENE_PARTICIPATES_IN_PATHWAY Meiotic recombination -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Meiotic recombination -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY Metalloprotease DUBs | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MLH3",
"source_db": "UniProt",
"payload": {
"accession": "Q9UHC1",
"sequence": "MIKCLSVEVQAKLRSGLAISSLGQCVEELALNSIDAEAKCVAVRVNMETFQVQVIDNGFGMGSDDVEKVGNRYFTSKCHSVQDLENPRFYGFRGEALANIADMASAVEISSKKNRTMKTFVKLFQSGKALKACE... | [
{
"source_db": "ClinVar",
"source_id": "MLH3",
"text": "NM_001040108.2(MLH3):c.980dup (p.Ile328fs) VARIANT_IN_GENE MLH3",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-912446",
"text": "MLH3 GENE_PARTICIPATES_IN_PATHWAY Meiotic recombination",
"confidence": 1
... | {
"variant": "NM_001040108.2(MLH3):c.980dup (p.Ile328fs)",
"pathway": "Metalloprotease DUBs"
} | 1 |
co_mech_00149 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000465.4(BARD1):c.1944del (p.Glu649fs) affects the Synthesis of PC pathway, citing each molecular step. | NM_000465.4(BARD1):c.1944del (p.Glu649fs) VARIANT_IN_GENE BARD1 -> BARD1 GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> ACHE GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> ACHE GENE_PARTICIPATES_IN_PATHWAY Synthesis of PC | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000465.4(BARD1):c.1944del (p.Glu649fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000465.4(BARD1):c.1944del (p.Glu649fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000465.4(BARD1):c.1944del (p.Glu649fs) VARIANT_IN_GENE BARD1 -> BARD1 GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> ACHE GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity -> ACHE GENE_PARTICIPATES_IN_PATHWAY Synthesis of PC | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BARD1",
"source_db": "UniProt",
"payload": {
"accession": "Q99728",
"sequence": "MPDNRQPRNRQPRIRSGNEPRSAPAMEPDGRGAWAHSRAALDRLEKLLRCSRCTNILREPVCLGGCEHIFCSNCVSDCIGTGCPVCYTPAWIQDLKINRQLDSMIQLCSKLRNLLHDNELSDLKEDKPRKSLF... | [
{
"source_db": "ClinVar",
"source_id": "BARD1",
"text": "NM_000465.4(BARD1):c.1944del (p.Glu649fs) VARIANT_IN_GENE BARD1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0042803",
"text": "BARD1 GENE_ANNOTATED_WITH_GO_TERM protein homodimerization activity",
"confidence... | {
"variant": "NM_000465.4(BARD1):c.1944del (p.Glu649fs)",
"pathway": "Synthesis of PC"
} | 0.774597 |
co_mech_00150 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000251.3(MSH2):c.1272_1276+6del affects the Epigenetic regulation of gene expression by MLL3 and MLL4 complexes pathway, citing each molecular step. | NM_000251.3(MSH2):c.1272_1276+6del VARIANT_IN_GENE MSH2 -> Single allele VARIANT_IN_GENE MSH2 -> Single allele VARIANT_IN_GENE KMT2C -> KMT2C GENE_PARTICIPATES_IN_PATHWAY Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000251.3(MSH2):c.1272_1276+6del",
"source_node_type": "VARIANT",
"source_node_label": "NM_000251.3(MSH2):c.1272_1276+6del",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edg... | NM_000251.3(MSH2):c.1272_1276+6del VARIANT_IN_GENE MSH2 -> Single allele VARIANT_IN_GENE MSH2 -> Single allele VARIANT_IN_GENE KMT2C -> KMT2C GENE_PARTICIPATES_IN_PATHWAY Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH2",
"source_db": "UniProt",
"payload": {
"accession": "P43246",
"sequence": "MAVQPKETLQLESAAEVGFVRFFQGMPEKPTTTVRLFDRGDFYTAHGEDALLAAREVFKTQGVIKYMGPAGAKNLQSVVLSKMNFESFVKDLLLVRQYRVEVYKNRAGNKASKENDWYLAYKASPGNLSQFEDI... | [
{
"source_db": "ClinVar",
"source_id": "MSH2",
"text": "NM_000251.3(MSH2):c.1272_1276+6del VARIANT_IN_GENE MSH2",
"confidence": 1
},
{
"source_db": "ClinVar",
"source_id": "Single allele",
"text": "Single allele VARIANT_IN_GENE MSH2",
"confidence": 1
},
{
"source_db": "Cl... | {
"variant": "NM_000251.3(MSH2):c.1272_1276+6del",
"pathway": "Epigenetic regulation of gene expression by MLL3 and MLL4 complexes"
} | 1 |
co_mech_00151 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_007194.4(CHEK2):c.363T>A (p.Cys121Ter) affects the Endogenous sterols pathway, citing each molecular step. | NM_007194.4(CHEK2):c.363T>A (p.Cys121Ter) VARIANT_IN_GENE CHEK2 -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> RXRA GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> RXRA GENE_PARTICIPATES_IN_PATHWAY Endogenous sterols | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007194.4(CHEK2):c.363T>A (p.Cys121Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007194.4(CHEK2):c.363T>A (p.Cys121Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_007194.4(CHEK2):c.363T>A (p.Cys121Ter) VARIANT_IN_GENE CHEK2 -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> RXRA GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> RXRA GENE_PARTICIPATES_IN_PATHWAY Endogenous sterols | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CHEK2",
"source_db": "UniProt",
"payload": {
"accession": "O96017",
"sequence": "MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTLSSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKSCEYCFDEPLLKRT... | [
{
"source_db": "ClinVar",
"source_id": "CHEK2",
"text": "NM_007194.4(CHEK2):c.363T>A (p.Cys121Ter) VARIANT_IN_GENE CHEK2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045893",
"text": "CHEK2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription"... | {
"variant": "NM_007194.4(CHEK2):c.363T>A (p.Cys121Ter)",
"pathway": "Endogenous sterols"
} | 0.774597 |
co_mech_00152 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000546.6(TP53):c.595_598del (p.Gly199fs) affects the Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane pathway, citing each molecular step. | NM_000546.6(TP53):c.595_598del (p.Gly199fs) VARIANT_IN_GENE TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY PKR-mediated signaling -> TUBA4A GENE_PARTICIPATES_IN_PATHWAY PKR-mediated signaling -> TUBA4A GENE_PARTICIPATES_IN_PATHWAY Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000546.6(TP53):c.595_598del (p.Gly199fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000546.6(TP53):c.595_598del (p.Gly199fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_000546.6(TP53):c.595_598del (p.Gly199fs) VARIANT_IN_GENE TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY PKR-mediated signaling -> TUBA4A GENE_PARTICIPATES_IN_PATHWAY PKR-mediated signaling -> TUBA4A GENE_PARTICIPATES_IN_PATHWAY Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "TP53",
"source_db": "UniProt",
"payload": {
"accession": "P04637",
"sequence": "MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMF... | [
{
"source_db": "ClinVar",
"source_id": "TP53",
"text": "NM_000546.6(TP53):c.595_598del (p.Gly199fs) VARIANT_IN_GENE TP53",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-9833482",
"text": "TP53 GENE_PARTICIPATES_IN_PATHWAY PKR-mediated signaling",
"confidence":... | {
"variant": "NM_000546.6(TP53):c.595_598del (p.Gly199fs)",
"pathway": "Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane"
} | 1 |
co_mech_00153 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_001008212.2(OPTN):c.666del (p.Lys223fs) affects the midostaurin-resistant FLT3 mutants pathway, citing each molecular step. | NM_001008212.2(OPTN):c.666del (p.Lys223fs) VARIANT_IN_GENE OPTN -> OPTN PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TBK1 -> TBK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_PARTICIPATES_IN_PATHWAY midostaurin-resistant FLT3 mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001008212.2(OPTN):c.666del (p.Lys223fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001008212.2(OPTN):c.666del (p.Lys223fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_001008212.2(OPTN):c.666del (p.Lys223fs) VARIANT_IN_GENE OPTN -> OPTN PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TBK1 -> TBK1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_PARTICIPATES_IN_PATHWAY midostaurin-resistant FLT3 mutants | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "OPTN",
"source_db": "UniProt",
"payload": {
"accession": "Q96CV9",
"sequence": "MSHQPLSCLTEKEDSPSESTGNGPPHLAHPNLDTFTPEELLQQMKELLTENHQLKEAMKLNNQAMKGRFEELSAWTEKQKEERQFFEIQSKEAKERLMALSHENEKLKEELGKLKGKSERSSEDPTDDSRLPRA... | [
{
"source_db": "ClinVar",
"source_id": "OPTN",
"text": "NM_001008212.2(OPTN):c.666del (p.Lys223fs) VARIANT_IN_GENE OPTN",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "TBK1",
"text": "OPTN PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TBK1",
"confidence": 0.999
},
{
"s... | {
"variant": "NM_001008212.2(OPTN):c.666del (p.Lys223fs)",
"pathway": "midostaurin-resistant FLT3 mutants"
} | 0.81503 |
co_mech_00154 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_058216.3(RAD51C):c.502A>T (p.Arg168Ter) affects the PPARA activates gene expression pathway, citing each molecular step. | NM_058216.3(RAD51C):c.502A>T (p.Arg168Ter) VARIANT_IN_GENE RAD51C -> RAD51C PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> RXRA GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> RXRA GENE_PARTICIPATES_... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_058216.3(RAD51C):c.502A>T (p.Arg168Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_058216.3(RAD51C):c.502A>T (p.Arg168Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_058216.3(RAD51C):c.502A>T (p.Arg168Ter) VARIANT_IN_GENE RAD51C -> RAD51C PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> RXRA GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> RXRA GENE_PARTICIPATES_... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "RAD51C",
"source_db": "UniProt",
"payload": {
"accession": "O43502",
"sequence": "MRGKTFRFEMQRDLVSFPLSPAVRVKLVSAGFQTAEELLEVKPSELSKEVGISKAEALETLQIIRRECLTNKPRYAGTSESHKKCTALELLEQEHTQGFIITFCSALDDILGGGVPLMKTTEICGAPGVGKT... | [
{
"source_db": "ClinVar",
"source_id": "RAD51C",
"text": "NM_058216.3(RAD51C):c.502A>T (p.Arg168Ter) VARIANT_IN_GENE RAD51C",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA2",
"text": "RAD51C PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2",
"confidence": 0.999
},
... | {
"variant": "NM_058216.3(RAD51C):c.502A>T (p.Arg168Ter)",
"pathway": "PPARA activates gene expression"
} | 0.81503 |
co_mech_00155 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_022552.5(DNMT3A):c.1761_1762dup (p.His588fs) affects the Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation pathway, citing each molecular step. | NM_022552.5(DNMT3A):c.1761_1762dup (p.His588fs) VARIANT_IN_GENE DNMT3A -> DNMT3A GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> SOD1 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> SOD1 GENE_PARTICIPATES_IN_PATHWAY Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_022552.5(DNMT3A):c.1761_1762dup (p.His588fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_022552.5(DNMT3A):c.1761_1762dup (p.His588fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_... | NM_022552.5(DNMT3A):c.1761_1762dup (p.His588fs) VARIANT_IN_GENE DNMT3A -> DNMT3A GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> SOD1 GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> SOD1 GENE_PARTICIPATES_IN_PATHWAY Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "DNMT3A",
"source_db": "UniProt",
"payload": {
"accession": "Q9Y6K1",
"sequence": "MPAMPSSGPGDTSSSAAEREEDRKDGEEQEEPRGKEERQEPSTTARKVGRPGRKRKHPPVESGDTPKDPAVISKSPSMAQDSGASELLPNGDLEKRSEPQPEEGSPAGGQKGGAPAEGEGAAETLPEASRAV... | [
{
"source_db": "ClinVar",
"source_id": "DNMT3A",
"text": "NM_022552.5(DNMT3A):c.1761_1762dup (p.His588fs) VARIANT_IN_GENE DNMT3A",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008270",
"text": "DNMT3A GENE_ANNOTATED_WITH_GO_TERM zinc ion binding",
"confidence": 0.6
... | {
"variant": "NM_022552.5(DNMT3A):c.1761_1762dup (p.His588fs)",
"pathway": "Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation"
} | 0.774597 |
co_mech_00156 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000465.4(BARD1):c.2135dup (p.Asp712fs) affects the RHOA GTPase cycle pathway, citing each molecular step. | NM_000465.4(BARD1):c.2135dup (p.Asp712fs) VARIANT_IN_GENE BARD1 -> BARD1 GENE_ANNOTATED_WITH_GO_TERM protein heterodimerization activity -> VAPB GENE_ANNOTATED_WITH_GO_TERM protein heterodimerization activity -> VAPB GENE_PARTICIPATES_IN_PATHWAY RHOA GTPase cycle | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000465.4(BARD1):c.2135dup (p.Asp712fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000465.4(BARD1):c.2135dup (p.Asp712fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000465.4(BARD1):c.2135dup (p.Asp712fs) VARIANT_IN_GENE BARD1 -> BARD1 GENE_ANNOTATED_WITH_GO_TERM protein heterodimerization activity -> VAPB GENE_ANNOTATED_WITH_GO_TERM protein heterodimerization activity -> VAPB GENE_PARTICIPATES_IN_PATHWAY RHOA GTPase cycle | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BARD1",
"source_db": "UniProt",
"payload": {
"accession": "Q99728",
"sequence": "MPDNRQPRNRQPRIRSGNEPRSAPAMEPDGRGAWAHSRAALDRLEKLLRCSRCTNILREPVCLGGCEHIFCSNCVSDCIGTGCPVCYTPAWIQDLKINRQLDSMIQLCSKLRNLLHDNELSDLKEDKPRKSLF... | [
{
"source_db": "ClinVar",
"source_id": "BARD1",
"text": "NM_000465.4(BARD1):c.2135dup (p.Asp712fs) VARIANT_IN_GENE BARD1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0046982",
"text": "BARD1 GENE_ANNOTATED_WITH_GO_TERM protein heterodimerization activity",
"confiden... | {
"variant": "NM_000465.4(BARD1):c.2135dup (p.Asp712fs)",
"pathway": "RHOA GTPase cycle"
} | 0.774597 |
co_mech_00157 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000059.4(BRCA2):c.5504dup (p.Asn1835fs) affects the Late endosomal microautophagy pathway, citing each molecular step. | NM_000059.4(BRCA2):c.5504dup (p.Asn1835fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM protease binding -> PINK1 GENE_ANNOTATED_WITH_GO_TERM protease binding -> PINK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PARK7 -> PARK7 GENE_PARTICIPATES_IN_PATHWAY Late endosomal microautophagy | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000059.4(BRCA2):c.5504dup (p.Asn1835fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000059.4(BRCA2):c.5504dup (p.Asn1835fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_000059.4(BRCA2):c.5504dup (p.Asn1835fs) VARIANT_IN_GENE BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM protease binding -> PINK1 GENE_ANNOTATED_WITH_GO_TERM protease binding -> PINK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PARK7 -> PARK7 GENE_PARTICIPATES_IN_PATHWAY Late endosomal microautophagy | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA2",
"source_db": "UniProt",
"payload": {
"accession": "P51587",
"sequence": "MPIGSKERPTFFEIFKTRCNKADLGPISLNWFEELSSEAPPYNSEPAEESEHKNNNYEPNLFKTPQRKPSYNQLASTPIIFKEQGLTLPLYQSPVKELDKFKLDLGRNVPNSRHKSLRTVKTKMDQADDVSCP... | [
{
"source_db": "ClinVar",
"source_id": "BRCA2",
"text": "NM_000059.4(BRCA2):c.5504dup (p.Asn1835fs) VARIANT_IN_GENE BRCA2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0002020",
"text": "BRCA2 GENE_ANNOTATED_WITH_GO_TERM protease binding",
"confidence": 0.6
},
{
... | {
"variant": "NM_000059.4(BRCA2):c.5504dup (p.Asn1835fs)",
"pathway": "Late endosomal microautophagy"
} | 0.81503 |
co_mech_00158 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000059.4(BRCA2):c.4593_4594del (p.Lys1531fs) affects the Loss of Nlp from mitotic centrosomes pathway, citing each molecular step. | NM_000059.4(BRCA2):c.4593_4594del (p.Lys1531fs) VARIANT_IN_GENE BRCA2 -> BRCA2 PROTEIN_MEMBER_OF_COMPLEX BRCA1 / BRCA2 / CCNA2 / CDK2... -> CCNA2 PROTEIN_MEMBER_OF_COMPLEX BRCA1 / BRCA2 / CCNA2 / CDK2... -> CDK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CCNA2 -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Loss of Nlp from mitotic cen... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000059.4(BRCA2):c.4593_4594del (p.Lys1531fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000059.4(BRCA2):c.4593_4594del (p.Lys1531fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_... | NM_000059.4(BRCA2):c.4593_4594del (p.Lys1531fs) VARIANT_IN_GENE BRCA2 -> BRCA2 PROTEIN_MEMBER_OF_COMPLEX BRCA1 / BRCA2 / CCNA2 / CDK2... -> CCNA2 PROTEIN_MEMBER_OF_COMPLEX BRCA1 / BRCA2 / CCNA2 / CDK2... -> CDK1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CCNA2 -> CDK1 GENE_PARTICIPATES_IN_PATHWAY Loss of Nlp from mitotic cen... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA2",
"source_db": "UniProt",
"payload": {
"accession": "P51587",
"sequence": "MPIGSKERPTFFEIFKTRCNKADLGPISLNWFEELSSEAPPYNSEPAEESEHKNNNYEPNLFKTPQRKPSYNQLASTPIIFKEQGLTLPLYQSPVKELDKFKLDLGRNVPNSRHKSLRTVKTKMDQADDVSCP... | [
{
"source_db": "ClinVar",
"source_id": "BRCA2",
"text": "NM_000059.4(BRCA2):c.4593_4594del (p.Lys1531fs) VARIANT_IN_GENE BRCA2",
"confidence": 1
},
{
"source_db": "OmniPath",
"source_id": "Compleat:HC6487",
"text": "BRCA2 PROTEIN_MEMBER_OF_COMPLEX BRCA1 / BRCA2 / CCNA2 / CDK2...",
... | {
"variant": "NM_000059.4(BRCA2):c.4593_4594del (p.Lys1531fs)",
"pathway": "Loss of Nlp from mitotic centrosomes"
} | 0.9998 |
co_mech_00159 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000465.4(BARD1):c.601del (p.Arg201fs) affects the Sphingolipid de novo biosynthesis pathway, citing each molecular step. | NM_000465.4(BARD1):c.601del (p.Arg201fs) VARIANT_IN_GENE BARD1 -> BARD1 GENE_ANNOTATED_WITH_GO_TERM protein heterodimerization activity -> VAPB GENE_ANNOTATED_WITH_GO_TERM protein heterodimerization activity -> VAPB GENE_PARTICIPATES_IN_PATHWAY Sphingolipid de novo biosynthesis | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000465.4(BARD1):c.601del (p.Arg201fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000465.4(BARD1):c.601del (p.Arg201fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_000465.4(BARD1):c.601del (p.Arg201fs) VARIANT_IN_GENE BARD1 -> BARD1 GENE_ANNOTATED_WITH_GO_TERM protein heterodimerization activity -> VAPB GENE_ANNOTATED_WITH_GO_TERM protein heterodimerization activity -> VAPB GENE_PARTICIPATES_IN_PATHWAY Sphingolipid de novo biosynthesis | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_000465.4(BARD1):c.601del (p.Arg201fs)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr2",
"pos": 214781273,
"track": "phyloP100way",
"window": 20,
"scores": [
0.0116299,
... | [
{
"source_db": "ClinVar",
"source_id": "BARD1",
"text": "NM_000465.4(BARD1):c.601del (p.Arg201fs) VARIANT_IN_GENE BARD1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0046982",
"text": "BARD1 GENE_ANNOTATED_WITH_GO_TERM protein heterodimerization activity",
"confidenc... | {
"variant": "NM_000465.4(BARD1):c.601del (p.Arg201fs)",
"pathway": "Sphingolipid de novo biosynthesis"
} | 0.774597 |
co_mech_00160 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_001211.6(BUB1B):c.1198A>T (p.Lys400Ter) affects the Formation of Senescence-Associated Heterochromatin Foci (SAHF) pathway, citing each molecular step. | NM_001211.6(BUB1B):c.1198A>T (p.Lys400Ter) VARIANT_IN_GENE BUB1B -> BIRC5 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BUB1B -> BIRC5 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH AURKA -> AURKA PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY Formation of Senescence-Associated Heterochromatin Foci (SAHF) | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001211.6(BUB1B):c.1198A>T (p.Lys400Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001211.6(BUB1B):c.1198A>T (p.Lys400Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_001211.6(BUB1B):c.1198A>T (p.Lys400Ter) VARIANT_IN_GENE BUB1B -> BIRC5 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BUB1B -> BIRC5 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH AURKA -> AURKA PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY Formation of Senescence-Associated Heterochromatin Foci (SAHF) | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BUB1B",
"source_db": "UniProt",
"payload": {
"accession": "O60566",
"sequence": "MAAVKKEGGALSEAMSLEGDEWELSKENVQPLRQGRIMSTLQGALAQESACNNTLQQQKRAFEYEIRFYTGNDPLDVWDRYISWTEQNYPQGGKESNMSTLLERAVEALQGEKRYYSDPRFLNLWLKLGRLCN... | [
{
"source_db": "ClinVar",
"source_id": "BUB1B",
"text": "NM_001211.6(BUB1B):c.1198A>T (p.Lys400Ter) VARIANT_IN_GENE BUB1B",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BIRC5",
"text": "BIRC5 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BUB1B",
"confidence": 0.987
},
{
... | {
"variant": "NM_001211.6(BUB1B):c.1198A>T (p.Lys400Ter)",
"pathway": "Formation of Senescence-Associated Heterochromatin Foci (SAHF)"
} | 0.995587 |
co_mech_00161 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_004360.5(CDH1):c.1143_1145delinsA (p.Gly382fs) affects the Signaling by LTK in cancer pathway, citing each molecular step. | NM_004360.5(CDH1):c.1143_1145delinsA (p.Gly382fs) VARIANT_IN_GENE CDH1 -> CDH1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH EGFR -> EGFR PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PIK3CA -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Signaling by LTK in cancer | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004360.5(CDH1):c.1143_1145delinsA (p.Gly382fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004360.5(CDH1):c.1143_1145delinsA (p.Gly382fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"e... | NM_004360.5(CDH1):c.1143_1145delinsA (p.Gly382fs) VARIANT_IN_GENE CDH1 -> CDH1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH EGFR -> EGFR PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH PIK3CA -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Signaling by LTK in cancer | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CDH1",
"source_db": "UniProt",
"payload": {
"accession": "P12830",
"sequence": "MGPWSRSLSALLLLLQVSSWLCQEPEPCHPGFDAESYTFTVPRRHLERGRVLGRVNFEDCTGRQRTAYFSLDTRFKVGTDGVITVKRPLRFHNPQIHFLVYAWDSTYRKFSTKVTLNTVGHHHRPPPHQASVSG... | [
{
"source_db": "ClinVar",
"source_id": "CDH1",
"text": "NM_004360.5(CDH1):c.1143_1145delinsA (p.Gly382fs) VARIANT_IN_GENE CDH1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "EGFR",
"text": "CDH1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH EGFR",
"confidence": 0.999
},
{... | {
"variant": "NM_004360.5(CDH1):c.1143_1145delinsA (p.Gly382fs)",
"pathway": "Signaling by LTK in cancer"
} | 0.9995 |
co_mech_00162 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000179.3(MSH6):c.962delinsAGAGCTAGTTGCT (p.Ser321Ter) affects the Activation of AKT2 pathway, citing each molecular step. | NM_000179.3(MSH6):c.962delinsAGAGCTAGTTGCT (p.Ser321Ter) VARIANT_IN_GENE MSH6 -> MSH6 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT2 GENE_PARTICIPATES_IN_PATHWAY Activation of AKT2 | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000179.3(MSH6):c.962delinsAGAGCTAGTTGCT (p.Ser321Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000179.3(MSH6):c.962delinsAGAGCTAGTTGCT (p.Ser321Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "cura... | NM_000179.3(MSH6):c.962delinsAGAGCTAGTTGCT (p.Ser321Ter) VARIANT_IN_GENE MSH6 -> MSH6 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> AKT2 GENE_PARTICIPATES_IN_PATHWAY Activation of AKT2 | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH6",
"source_db": "UniProt",
"payload": {
"accession": "P52701",
"sequence": "MSRQSTLYSFFPKSPALSDANKASARASREGGRAAAAPGASPSPGGDAAWSEAGPGPRPLARSASPPKAKNLNGGLRRSVAPAAPTSCDFSPGDLVWAKMEGYPWWPCLVYNHPFDGTFIREKGKSVRVHVQFF... | [
{
"source_db": "ClinVar",
"source_id": "MSH6",
"text": "NM_000179.3(MSH6):c.962delinsAGAGCTAGTTGCT (p.Ser321Ter) VARIANT_IN_GENE MSH6",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "MSH6 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
}... | {
"variant": "NM_000179.3(MSH6):c.962delinsAGAGCTAGTTGCT (p.Ser321Ter)",
"pathway": "Activation of AKT2"
} | 0.774597 |
co_mech_00163 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_170606.3(KMT2C):c.749G>A (p.Trp250Ter) affects the Clathrin-mediated endocytosis pathway, citing each molecular step. | NM_170606.3(KMT2C):c.749G>A (p.Trp250Ter) VARIANT_IN_GENE KMT2C -> KMT2C GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_PARTICIPATES_IN_PATHWAY Clathrin-mediated endocytosis | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_170606.3(KMT2C):c.749G>A (p.Trp250Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_170606.3(KMT2C):c.749G>A (p.Trp250Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_170606.3(KMT2C):c.749G>A (p.Trp250Ter) VARIANT_IN_GENE KMT2C -> KMT2C GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_PARTICIPATES_IN_PATHWAY Clathrin-mediated endocytosis | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KMT2C",
"source_db": "UniProt",
"payload": {
"accession": "Q8NEZ4",
"sequence": "MSSEEDKSVEQPQPPPPPPEEPGAPAPSPAAADKRPRGRPRKDGASPFQRARKKPRSRGKTAVEDEDSMDGLETTETETIVETEIKEQSAEEDAEAEVDNSKQLIPTLQRSVSEESANSLVSVGVEAKISEQL... | [
{
"source_db": "ClinVar",
"source_id": "KMT2C",
"text": "NM_170606.3(KMT2C):c.749G>A (p.Trp250Ter) VARIANT_IN_GENE KMT2C",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045944",
"text": "KMT2C GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymer... | {
"variant": "NM_170606.3(KMT2C):c.749G>A (p.Trp250Ter)",
"pathway": "Clathrin-mediated endocytosis"
} | 0.774597 |
co_mech_00164 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_000038.6(APC):c.1171del (p.Ile391fs) affects the Regulation of MITF-M-dependent genes involved in pigmentation pathway, citing each molecular step. | NM_000038.6(APC):c.1171del (p.Ile391fs) VARIANT_IN_GENE APC -> APC PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Regulation of MITF-M-dependent genes involved in pigmentation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000038.6(APC):c.1171del (p.Ile391fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000038.6(APC):c.1171del (p.Ile391fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000038.6(APC):c.1171del (p.Ile391fs) VARIANT_IN_GENE APC -> APC PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY Regulation of MITF-M-dependent genes involved in pigmentation | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "APC",
"source_db": "UniProt",
"payload": {
"accession": "P25054",
"sequence": "MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTKLETEASNMKEVLKQLQGSIEDEAMASSGQIDLLERLKELNLDSSNFPGVKLRSKMSLRSYGSREGSVSSRSGECSPVPMGSFPRRGFVNGSRESTGYLE... | [
{
"source_db": "ClinVar",
"source_id": "APC",
"text": "NM_000038.6(APC):c.1171del (p.Ile391fs) VARIANT_IN_GENE APC",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "CTNNB1",
"text": "APC PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1",
"confidence": 0.999
},
{
"sou... | {
"variant": "NM_000038.6(APC):c.1171del (p.Ile391fs)",
"pathway": "Regulation of MITF-M-dependent genes involved in pigmentation"
} | 0.999667 |
co_mech_00165 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_032043.3(BRIP1):c.781dup (p.Arg261fs) affects the Sensory processing of sound by inner hair cells of the cochlea pathway, citing each molecular step. | NM_032043.3(BRIP1):c.781dup (p.Arg261fs) VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BARD1 -> BARD1 GENE_PARTICIPATES_IN_PATHWAY UCH proteinases -> ACTB GENE_PARTICIPATES_IN_PATHWAY UCH proteinases -> ACTB GENE_PARTICIPATES_IN_PATHWAY Sensory processing of sound by inner hair cells of the cochle... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_032043.3(BRIP1):c.781dup (p.Arg261fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_032043.3(BRIP1):c.781dup (p.Arg261fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_032043.3(BRIP1):c.781dup (p.Arg261fs) VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BARD1 -> BARD1 GENE_PARTICIPATES_IN_PATHWAY UCH proteinases -> ACTB GENE_PARTICIPATES_IN_PATHWAY UCH proteinases -> ACTB GENE_PARTICIPATES_IN_PATHWAY Sensory processing of sound by inner hair cells of the cochle... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRIP1",
"source_db": "UniProt",
"payload": {
"accession": "Q9BX63",
"sequence": "MSSMWSEYTIGGVKIYFPYKAYPSQLAMMNSILRGLNSKQHCLLESPTGSGKSLALLCSALAWQQSLSGKPADEGVSEKAEVQLSCCCACHSKDFTNNDMNQGTSRHFNYPSTPPSERNGTSSTCQDSPEKTT... | [
{
"source_db": "ClinVar",
"source_id": "BRIP1",
"text": "NM_032043.3(BRIP1):c.781dup (p.Arg261fs) VARIANT_IN_GENE BRIP1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BARD1",
"text": "BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BARD1",
"confidence": 0.999
},
{
... | {
"variant": "NM_032043.3(BRIP1):c.781dup (p.Arg261fs)",
"pathway": "Sensory processing of sound by inner hair cells of the cochlea"
} | 0.9998 |
co_mech_00166 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000314.8(PTEN):c.79T>A (p.Tyr27Asn) affects the RHO GTPases activate IQGAPs pathway, citing each molecular step. | NM_000314.8(PTEN):c.79T>A (p.Tyr27Asn) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_PARTICIPATES_IN_PATHWAY RHO GTPases activate IQGAPs | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000314.8(PTEN):c.79T>A (p.Tyr27Asn)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000314.8(PTEN):c.79T>A (p.Tyr27Asn)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000314.8(PTEN):c.79T>A (p.Tyr27Asn) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_PARTICIPATES_IN_PATHWAY RHO GTPases activate IQGAPs | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PTEN",
"source_db": "UniProt",
"payload": {
"accession": "P60484",
"sequence": "MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVM... | [
{
"source_db": "ClinVar",
"source_id": "PTEN",
"text": "NM_000314.8(PTEN):c.79T>A (p.Tyr27Asn) VARIANT_IN_GENE PTEN",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0030336",
"text": "PTEN GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration",
"confidence":... | {
"variant": "NM_000314.8(PTEN):c.79T>A (p.Tyr27Asn)",
"pathway": "RHO GTPases activate IQGAPs"
} | 0.774597 |
co_mech_00167 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_001288705.3(CSF1R):c.2060dup (p.Ser688fs) affects the Activated NTRK2 signals through FYN pathway, citing each molecular step. | NM_001288705.3(CSF1R):c.2060dup (p.Ser688fs) VARIANT_IN_GENE CSF1R -> CSF1R GENE_ANNOTATED_WITH_GO_TERM axon guidance -> BDNF GENE_ANNOTATED_WITH_GO_TERM axon guidance -> BDNF GENE_PARTICIPATES_IN_PATHWAY Activated NTRK2 signals through FYN | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001288705.3(CSF1R):c.2060dup (p.Ser688fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001288705.3(CSF1R):c.2060dup (p.Ser688fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_001288705.3(CSF1R):c.2060dup (p.Ser688fs) VARIANT_IN_GENE CSF1R -> CSF1R GENE_ANNOTATED_WITH_GO_TERM axon guidance -> BDNF GENE_ANNOTATED_WITH_GO_TERM axon guidance -> BDNF GENE_PARTICIPATES_IN_PATHWAY Activated NTRK2 signals through FYN | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CSF1R",
"source_db": "UniProt",
"payload": {
"accession": "P07333",
"sequence": "MGPGVLLLLLVATAWHGQGIPVIEPSVPELVVKPGATVTLRCVGNGSVEWDGPPSPHWTLYSDGSSSILSTNNATFQNTGTYRCTEPGDPLGGSAAIHLYVKDPARPWNVLAQEVVVFEDQDALLPCLLTDPV... | [
{
"source_db": "ClinVar",
"source_id": "CSF1R",
"text": "NM_001288705.3(CSF1R):c.2060dup (p.Ser688fs) VARIANT_IN_GENE CSF1R",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0007411",
"text": "CSF1R GENE_ANNOTATED_WITH_GO_TERM axon guidance",
"confidence": 0.6
},
{
... | {
"variant": "NM_001288705.3(CSF1R):c.2060dup (p.Ser688fs)",
"pathway": "Activated NTRK2 signals through FYN"
} | 0.774597 |
co_mech_00168 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_004333.6(BRAF):c.1802A>T (p.Lys601Ile) affects the Activated NTRK2 signals through PLCG1 pathway, citing each molecular step. | NM_004333.6(BRAF):c.1802A>T (p.Lys601Ile) VARIANT_IN_GENE BRAF -> BRAF PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY Activated NTRK2 signals through FRS2 and FRS3 -> BDNF GENE_PARTICIPATES_IN_PATHWAY Activated NTRK2 signals through FRS2 and FRS3 -> BDNF GENE_PARTICIPATES_IN_PATHWAY Acti... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004333.6(BRAF):c.1802A>T (p.Lys601Ile)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004333.6(BRAF):c.1802A>T (p.Lys601Ile)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_004333.6(BRAF):c.1802A>T (p.Lys601Ile) VARIANT_IN_GENE BRAF -> BRAF PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS -> NRAS GENE_PARTICIPATES_IN_PATHWAY Activated NTRK2 signals through FRS2 and FRS3 -> BDNF GENE_PARTICIPATES_IN_PATHWAY Activated NTRK2 signals through FRS2 and FRS3 -> BDNF GENE_PARTICIPATES_IN_PATHWAY Acti... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRAF",
"source_db": "UniProt",
"payload": {
"accession": "P15056",
"sequence": "MAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQEHIEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLGNGTDFSVSSSASMDTVTSSSSSSLSVLPSS... | [
{
"source_db": "ClinVar",
"source_id": "BRAF",
"text": "NM_004333.6(BRAF):c.1802A>T (p.Lys601Ile) VARIANT_IN_GENE BRAF",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "NRAS",
"text": "BRAF PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH NRAS",
"confidence": 0.999
},
{
"so... | {
"variant": "NM_004333.6(BRAF):c.1802A>T (p.Lys601Ile)",
"pathway": "Activated NTRK2 signals through PLCG1"
} | 0.9998 |
co_mech_00169 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000249.4(MLH1):c.2103+2T>A affects the Oxidative Stress Induced Senescence pathway, citing each molecular step. | NM_000249.4(MLH1):c.2103+2T>A VARIANT_IN_GENE MLH1 -> MLH1 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> TP53 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> TP53 GENE_PARTICIPATES_IN_PATHWAY Oxidative Stress Induced Senescence | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000249.4(MLH1):c.2103+2T>A",
"source_node_type": "VARIANT",
"source_node_label": "NM_000249.4(MLH1):c.2103+2T>A",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_d... | NM_000249.4(MLH1):c.2103+2T>A VARIANT_IN_GENE MLH1 -> MLH1 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> TP53 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes -> TP53 GENE_PARTICIPATES_IN_PATHWAY Oxidative Stress Induced Senescence | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MLH1",
"source_db": "UniProt",
"payload": {
"accession": "P40692",
"sequence": "MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGK... | [
{
"source_db": "ClinVar",
"source_id": "MLH1",
"text": "NM_000249.4(MLH1):c.2103+2T>A VARIANT_IN_GENE MLH1",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-6796648",
"text": "MLH1 GENE_PARTICIPATES_IN_PATHWAY TP53 Regulates Transcription of DNA Repair Genes",
"... | {
"variant": "NM_000249.4(MLH1):c.2103+2T>A",
"pathway": "Oxidative Stress Induced Senescence"
} | 1 |
co_mech_00170 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_004360.5(CDH1):c.464_467dup (p.Trp156Ter) affects the Regulation of MECP2 expression and activity pathway, citing each molecular step. | NM_004360.5(CDH1):c.464_467dup (p.Trp156Ter) VARIANT_IN_GENE CDH1 -> CDH1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CAMK4 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CAMK4 GENE_PARTICIPATES_IN_PATHWAY Regulation of MECP2 expression and activi... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004360.5(CDH1):c.464_467dup (p.Trp156Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004360.5(CDH1):c.464_467dup (p.Trp156Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_004360.5(CDH1):c.464_467dup (p.Trp156Ter) VARIANT_IN_GENE CDH1 -> CDH1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CAMK4 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CAMK4 GENE_PARTICIPATES_IN_PATHWAY Regulation of MECP2 expression and activi... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CDH1",
"source_db": "UniProt",
"payload": {
"accession": "P12830",
"sequence": "MGPWSRSLSALLLLLQVSSWLCQEPEPCHPGFDAESYTFTVPRRHLERGRVLGRVNFEDCTGRQRTAYFSLDTRFKVGTDGVITVKRPLRFHNPQIHFLVYAWDSTYRKFSTKVTLNTVGHHHRPPPHQASVSG... | [
{
"source_db": "ClinVar",
"source_id": "CDH1",
"text": "NM_004360.5(CDH1):c.464_467dup (p.Trp156Ter) VARIANT_IN_GENE CDH1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045893",
"text": "CDH1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription"... | {
"variant": "NM_004360.5(CDH1):c.464_467dup (p.Trp156Ter)",
"pathway": "Regulation of MECP2 expression and activity"
} | 0.774597 |
co_mech_00171 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000179.3(MSH6):c.644_645insCT (p.Val215_Thr216insTer) affects the Formation of the ureteric bud pathway, citing each molecular step. | NM_000179.3(MSH6):c.644_645insCT (p.Val215_Thr216insTer) VARIANT_IN_GENE MSH6 -> MSH6 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> RET GENE_ANNOTATED_WITH_GO_TERM ATP binding -> RET GENE_PARTICIPATES_IN_PATHWAY Formation of the ureteric bud | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000179.3(MSH6):c.644_645insCT (p.Val215_Thr216insTer)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000179.3(MSH6):c.644_645insCT (p.Val215_Thr216insTer)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "cura... | NM_000179.3(MSH6):c.644_645insCT (p.Val215_Thr216insTer) VARIANT_IN_GENE MSH6 -> MSH6 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> RET GENE_ANNOTATED_WITH_GO_TERM ATP binding -> RET GENE_PARTICIPATES_IN_PATHWAY Formation of the ureteric bud | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "MSH6",
"source_db": "UniProt",
"payload": {
"accession": "P52701",
"sequence": "MSRQSTLYSFFPKSPALSDANKASARASREGGRAAAAPGASPSPGGDAAWSEAGPGPRPLARSASPPKAKNLNGGLRRSVAPAAPTSCDFSPGDLVWAKMEGYPWWPCLVYNHPFDGTFIREKGKSVRVHVQFF... | [
{
"source_db": "ClinVar",
"source_id": "MSH6",
"text": "NM_000179.3(MSH6):c.644_645insCT (p.Val215_Thr216insTer) VARIANT_IN_GENE MSH6",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "MSH6 GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
}... | {
"variant": "NM_000179.3(MSH6):c.644_645insCT (p.Val215_Thr216insTer)",
"pathway": "Formation of the ureteric bud"
} | 0.774597 |
co_mech_00172 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_001097577.3(ANG):c.189C>G (p.Cys63Trp) affects the SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription pathway, citing each molecular step. | NM_001097577.3(ANG):c.189C>G (p.Cys63Trp) VARIANT_IN_GENE ANG -> ANG GENE_ANNOTATED_WITH_GO_TERM negative regulation of apoptotic process -> MYC GENE_ANNOTATED_WITH_GO_TERM negative regulation of apoptotic process -> MYC GENE_PARTICIPATES_IN_PATHWAY SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001097577.3(ANG):c.189C>G (p.Cys63Trp)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001097577.3(ANG):c.189C>G (p.Cys63Trp)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_001097577.3(ANG):c.189C>G (p.Cys63Trp) VARIANT_IN_GENE ANG -> ANG GENE_ANNOTATED_WITH_GO_TERM negative regulation of apoptotic process -> MYC GENE_ANNOTATED_WITH_GO_TERM negative regulation of apoptotic process -> MYC GENE_PARTICIPATES_IN_PATHWAY SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_001097577.3(ANG):c.189C>G (p.Cys63Trp)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr14",
"pos": 20693753,
"track": "phyloP100way",
"window": 20,
"scores": [
-0.22641699999999... | [
{
"source_db": "ClinVar",
"source_id": "ANG",
"text": "NM_001097577.3(ANG):c.189C>G (p.Cys63Trp) VARIANT_IN_GENE ANG",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0043066",
"text": "ANG GENE_ANNOTATED_WITH_GO_TERM negative regulation of apoptotic process",
"confidenc... | {
"variant": "NM_001097577.3(ANG):c.189C>G (p.Cys63Trp)",
"pathway": "SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription"
} | 0.774597 |
co_mech_00173 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_006231.4(POLE):c.2468+1G>T affects the RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression pathway, citing each molecular step. | NM_006231.4(POLE):c.2468+1G>T VARIANT_IN_GENE POLE -> POLE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> RXRA GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> RXRA GENE_PARTICIPATES_IN_PATHWAY RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_006231.4(POLE):c.2468+1G>T",
"source_node_type": "VARIANT",
"source_node_label": "NM_006231.4(POLE):c.2468+1G>T",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_d... | NM_006231.4(POLE):c.2468+1G>T VARIANT_IN_GENE POLE -> POLE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> RXRA GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> RXRA GENE_PARTICIPATES_IN_PATHWAY RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "POLE",
"source_db": "UniProt",
"payload": {
"accession": "Q07864",
"sequence": "MSLRSGGRRRADPGADGEASRDDGATSSVSALKRLERSQWTDKMDLRFGFERLKEPGEKTGWLINMHPTEILDEDKRLGSAVDYYFIQDDGSRFKVALPYKPYFYIATRKGCEREVSSFLSKKFQGKIAKVETV... | [
{
"source_db": "ClinVar",
"source_id": "POLE",
"text": "NM_006231.4(POLE):c.2468+1G>T VARIANT_IN_GENE POLE",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008270",
"text": "POLE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding",
"confidence": 0.6
},
{
"source_db":... | {
"variant": "NM_006231.4(POLE):c.2468+1G>T",
"pathway": "RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression"
} | 0.774597 |
co_mech_00174 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_006231.4(POLE):c.802-2A>G affects the TRAF3-dependent IRF activation pathway pathway, citing each molecular step. | NM_006231.4(POLE):c.802-2A>G VARIANT_IN_GENE POLE -> POLE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CREBBP GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CREBBP GENE_PARTICIPATES_IN_PATHWAY TRAF3-dependent IRF activation pathway | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_006231.4(POLE):c.802-2A>G",
"source_node_type": "VARIANT",
"source_node_label": "NM_006231.4(POLE):c.802-2A>G",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_db"... | NM_006231.4(POLE):c.802-2A>G VARIANT_IN_GENE POLE -> POLE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CREBBP GENE_ANNOTATED_WITH_GO_TERM zinc ion binding -> CREBBP GENE_PARTICIPATES_IN_PATHWAY TRAF3-dependent IRF activation pathway | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "POLE",
"source_db": "UniProt",
"payload": {
"accession": "Q07864",
"sequence": "MSLRSGGRRRADPGADGEASRDDGATSSVSALKRLERSQWTDKMDLRFGFERLKEPGEKTGWLINMHPTEILDEDKRLGSAVDYYFIQDDGSRFKVALPYKPYFYIATRKGCEREVSSFLSKKFQGKIAKVETV... | [
{
"source_db": "ClinVar",
"source_id": "POLE",
"text": "NM_006231.4(POLE):c.802-2A>G VARIANT_IN_GENE POLE",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008270",
"text": "POLE GENE_ANNOTATED_WITH_GO_TERM zinc ion binding",
"confidence": 0.6
},
{
"source_db": ... | {
"variant": "NM_006231.4(POLE):c.802-2A>G",
"pathway": "TRAF3-dependent IRF activation pathway"
} | 0.774597 |
co_mech_00175 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000546.6(TP53):c.1168_1171dup (p.Asp391delinsAlaTer) affects the Signaling by RAS GAP mutants pathway, citing each molecular step. | NM_000546.6(TP53):c.1168_1171dup (p.Asp391delinsAlaTer) VARIANT_IN_GENE TP53 -> TP53 GENE_ANNOTATED_WITH_GO_TERM positive regulation of cellular senescence -> KRAS GENE_ANNOTATED_WITH_GO_TERM positive regulation of cellular senescence -> KRAS GENE_PARTICIPATES_IN_PATHWAY Signaling by RAS GAP mutants | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000546.6(TP53):c.1168_1171dup (p.Asp391delinsAlaTer)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000546.6(TP53):c.1168_1171dup (p.Asp391delinsAlaTer)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curate... | NM_000546.6(TP53):c.1168_1171dup (p.Asp391delinsAlaTer) VARIANT_IN_GENE TP53 -> TP53 GENE_ANNOTATED_WITH_GO_TERM positive regulation of cellular senescence -> KRAS GENE_ANNOTATED_WITH_GO_TERM positive regulation of cellular senescence -> KRAS GENE_PARTICIPATES_IN_PATHWAY Signaling by RAS GAP mutants | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "TP53",
"source_db": "UniProt",
"payload": {
"accession": "P04637",
"sequence": "MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMF... | [
{
"source_db": "ClinVar",
"source_id": "TP53",
"text": "NM_000546.6(TP53):c.1168_1171dup (p.Asp391delinsAlaTer) VARIANT_IN_GENE TP53",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:2000774",
"text": "TP53 GENE_ANNOTATED_WITH_GO_TERM positive regulation of cellular senescen... | {
"variant": "NM_000546.6(TP53):c.1168_1171dup (p.Asp391delinsAlaTer)",
"pathway": "Signaling by RAS GAP mutants"
} | 0.774597 |
co_mech_00176 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_015338.6(ASXL1):c.4254_4260delinsCTCAC (p.Lys1419fs) affects the Respiratory syncytial virus (RSV) attachment and entry pathway, citing each molecular step. | NM_015338.6(ASXL1):c.4254_4260delinsCTCAC (p.Lys1419fs) VARIANT_IN_GENE ASXL1 -> ASXL1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_PARTICIPATES_IN_PATHWAY Respiratory sync... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_015338.6(ASXL1):c.4254_4260delinsCTCAC (p.Lys1419fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_015338.6(ASXL1):c.4254_4260delinsCTCAC (p.Lys1419fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curate... | NM_015338.6(ASXL1):c.4254_4260delinsCTCAC (p.Lys1419fs) VARIANT_IN_GENE ASXL1 -> ASXL1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription by RNA polymerase II -> EGFR GENE_PARTICIPATES_IN_PATHWAY Respiratory sync... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ASXL1",
"source_db": "UniProt",
"payload": {
"accession": "Q8IXJ9",
"sequence": "MKDKQKKKKERTWAEAARLVLENYSDAPMTPKQILQVIEAEGLKEMRSGTSPLACLNAMLHSNSRGGEGLFYKLPGRISLFTLKKDALQWSRHPATVEGEEPEDTADVESCGSNEASTVSGENDVSLDETSSN... | [
{
"source_db": "ClinVar",
"source_id": "ASXL1",
"text": "NM_015338.6(ASXL1):c.4254_4260delinsCTCAC (p.Lys1419fs) VARIANT_IN_GENE ASXL1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045944",
"text": "ASXL1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of transcription ... | {
"variant": "NM_015338.6(ASXL1):c.4254_4260delinsCTCAC (p.Lys1419fs)",
"pathway": "Respiratory syncytial virus (RSV) attachment and entry"
} | 0.774597 |
co_mech_00177 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_003482.4(KMT2D):c.6323dup (p.Gln2109fs) affects the ERBB2 Activates PTK6 Signaling pathway, citing each molecular step. | NM_003482.4(KMT2D):c.6323dup (p.Gln2109fs) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> EGFR GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> EGFR GENE_PARTICIPATES_IN_PATHWAY ERBB2 Activates PTK6 Signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_003482.4(KMT2D):c.6323dup (p.Gln2109fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_003482.4(KMT2D):c.6323dup (p.Gln2109fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_003482.4(KMT2D):c.6323dup (p.Gln2109fs) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> EGFR GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferation -> EGFR GENE_PARTICIPATES_IN_PATHWAY ERBB2 Activates PTK6 Signaling | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KMT2D",
"source_db": "UniProt",
"payload": {
"accession": "O14686",
"sequence": "MDSQKLAGEDKDSEPAADGPAASEDPSATESDLPNPHVGEVSVLSSGSPRLQETPQDCSGGPVRRCALCNCGEPSLHGQRELRRFELPFDWPRCPVVSPGGSPGPNEAVLPSEDLSQIGFPEGLTPAHLGEPG... | [
{
"source_db": "ClinVar",
"source_id": "KMT2D",
"text": "NM_003482.4(KMT2D):c.6323dup (p.Gln2109fs) VARIANT_IN_GENE KMT2D",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0008284",
"text": "KMT2D GENE_ANNOTATED_WITH_GO_TERM positive regulation of cell population proliferati... | {
"variant": "NM_003482.4(KMT2D):c.6323dup (p.Gln2109fs)",
"pathway": "ERBB2 Activates PTK6 Signaling"
} | 0.774597 |
co_mech_00178 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000057.4(BLM):c.2258T>A (p.Leu753Ter) affects the VEGF pathway, citing each molecular step. | NM_000057.4(BLM):c.2258T>A (p.Leu753Ter) VARIANT_IN_GENE BLM -> BLM GENE_PARTICIPATES_IN_PATHWAY SUMOylation of DNA damage response and repair proteins -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY SUMOylation of DNA damage response and repair proteins -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY VEGF | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000057.4(BLM):c.2258T>A (p.Leu753Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000057.4(BLM):c.2258T>A (p.Leu753Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_000057.4(BLM):c.2258T>A (p.Leu753Ter) VARIANT_IN_GENE BLM -> BLM GENE_PARTICIPATES_IN_PATHWAY SUMOylation of DNA damage response and repair proteins -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY SUMOylation of DNA damage response and repair proteins -> BRCA1 GENE_PARTICIPATES_IN_PATHWAY VEGF | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BLM",
"source_db": "UniProt",
"payload": {
"accession": "P54132",
"sequence": "MAAVPQNNLQEQLERHSARTLNNKLSLSKPKFSGFTFKKKTSSDNNVSVTNVSVAKTPVLRNKDVNVTEDFSFSEPLPNTTNQQRVKDFFKNAPAGQETQRGGSKSLLPDFLQTPKEVVCTTQNTPTVKKSRDTA... | [
{
"source_db": "ClinVar",
"source_id": "BLM",
"text": "NM_000057.4(BLM):c.2258T>A (p.Leu753Ter) VARIANT_IN_GENE BLM",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-3108214",
"text": "BLM GENE_PARTICIPATES_IN_PATHWAY SUMOylation of DNA damage response and repair pr... | {
"variant": "NM_000057.4(BLM):c.2258T>A (p.Leu753Ter)",
"pathway": "VEGF"
} | 0.960185 |
co_mech_00179 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_004360.5(CDH1):c.1228G>T (p.Glu410Ter) affects the CHD6, CHD7, CHD8, CHD9 subfamily pathway, citing each molecular step. | NM_004360.5(CDH1):c.1228G>T (p.Glu410Ter) VARIANT_IN_GENE CDH1 -> CDH1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY CHD6, CHD7, CHD8, CHD9 subfamily | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004360.5(CDH1):c.1228G>T (p.Glu410Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004360.5(CDH1):c.1228G>T (p.Glu410Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_004360.5(CDH1):c.1228G>T (p.Glu410Ter) VARIANT_IN_GENE CDH1 -> CDH1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY CHD6, CHD7, CHD8, CHD9 subfamily | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CDH1",
"source_db": "UniProt",
"payload": {
"accession": "P12830",
"sequence": "MGPWSRSLSALLLLLQVSSWLCQEPEPCHPGFDAESYTFTVPRRHLERGRVLGRVNFEDCTGRQRTAYFSLDTRFKVGTDGVITVKRPLRFHNPQIHFLVYAWDSTYRKFSTKVTLNTVGHHHRPPPHQASVSG... | [
{
"source_db": "ClinVar",
"source_id": "CDH1",
"text": "NM_004360.5(CDH1):c.1228G>T (p.Glu410Ter) VARIANT_IN_GENE CDH1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "CTNNB1",
"text": "CDH1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1",
"confidence": 0.999
},
{
... | {
"variant": "NM_004360.5(CDH1):c.1228G>T (p.Glu410Ter)",
"pathway": "CHD6, CHD7, CHD8, CHD9 subfamily"
} | 0.999667 |
co_mech_00180 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_007194.4(CHEK2):c.1341del (p.Phe447fs) affects the Developmental Lineage of Mammary Gland Myoepithelial Cells pathway, citing each molecular step. | NM_007194.4(CHEK2):c.1341del (p.Phe447fs) VARIANT_IN_GENE CHEK2 -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Developmental Lineage of Mammary Gland Myoep... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007194.4(CHEK2):c.1341del (p.Phe447fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007194.4(CHEK2):c.1341del (p.Phe447fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_007194.4(CHEK2):c.1341del (p.Phe447fs) VARIANT_IN_GENE CHEK2 -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Developmental Lineage of Mammary Gland Myoep... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "CHEK2",
"source_db": "UniProt",
"payload": {
"accession": "O96017",
"sequence": "MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTLSSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKSCEYCFDEPLLKRT... | [
{
"source_db": "ClinVar",
"source_id": "CHEK2",
"text": "NM_007194.4(CHEK2):c.1341del (p.Phe447fs) VARIANT_IN_GENE CHEK2",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0045893",
"text": "CHEK2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription"... | {
"variant": "NM_007194.4(CHEK2):c.1341del (p.Phe447fs)",
"pathway": "Developmental Lineage of Mammary Gland Myoepithelial Cells"
} | 0.774597 |
co_mech_00181 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NC_000011.9:g.(?_108163336)_(108170622_?)del affects the Activated NTRK2 signals through CDK5 pathway, citing each molecular step. | NC_000011.9:g.(?_108163336)_(108170622_?)del VARIANT_IN_GENE ATM -> ATM PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MSH2 -> MSH2 GENE_ANNOTATED_WITH_GO_TERM negative regulation of neuron apoptotic process -> BDNF GENE_ANNOTATED_WITH_GO_TERM negative regulation of neuron apoptotic process -> BDNF GENE_PARTICIPATES_IN_PATHWAY A... | {
"steps": [
{
"hop": 1,
"source_node_id": "NC_000011.9:g.(?_108163336)_(108170622_?)del",
"source_node_type": "VARIANT",
"source_node_label": "NC_000011.9:g.(?_108163336)_(108170622_?)del",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NC_000011.9:g.(?_108163336)_(108170622_?)del VARIANT_IN_GENE ATM -> ATM PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MSH2 -> MSH2 GENE_ANNOTATED_WITH_GO_TERM negative regulation of neuron apoptotic process -> BDNF GENE_ANNOTATED_WITH_GO_TERM negative regulation of neuron apoptotic process -> BDNF GENE_PARTICIPATES_IN_PATHWAY A... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ATM",
"source_db": "UniProt",
"payload": {
"accession": "Q13315",
"sequence": "MSLVLNDLLICCRQLEHDRATERKKEVEKFKRLIRDPETIKHLDRHSDSKQGKYLNWDAVFRFLQKYIQKETECLRIAKPNVSASTQASRQKKMQEISSLVKYFIKCANRRAPRLKCQELLNYIMDTVKDSSNGA... | [
{
"source_db": "ClinVar",
"source_id": "ATM",
"text": "NC_000011.9:g.(?_108163336)_(108170622_?)del VARIANT_IN_GENE ATM",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "MSH2",
"text": "ATM PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MSH2",
"confidence": 0.999
},
{
"so... | {
"variant": "NC_000011.9:g.(?_108163336)_(108170622_?)del",
"pathway": "Activated NTRK2 signals through CDK5"
} | 0.81503 |
co_mech_00182 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000546.6(TP53):c.560-19_560-9del affects the RET signaling pathway, citing each molecular step. | NM_000546.6(TP53):c.560-19_560-9del VARIANT_IN_GENE TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY Signaling by ALK fusions and activated point mutants -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Signaling by ALK fusions and activated point mutants -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY RET signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000546.6(TP53):c.560-19_560-9del",
"source_node_type": "VARIANT",
"source_node_label": "NM_000546.6(TP53):c.560-19_560-9del",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"e... | NM_000546.6(TP53):c.560-19_560-9del VARIANT_IN_GENE TP53 -> TP53 GENE_PARTICIPATES_IN_PATHWAY Signaling by ALK fusions and activated point mutants -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY Signaling by ALK fusions and activated point mutants -> PIK3CA GENE_PARTICIPATES_IN_PATHWAY RET signaling | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "TP53",
"source_db": "UniProt",
"payload": {
"accession": "P04637",
"sequence": "MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMF... | [
{
"source_db": "ClinVar",
"source_id": "TP53",
"text": "NM_000546.6(TP53):c.560-19_560-9del VARIANT_IN_GENE TP53",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-9725370",
"text": "TP53 GENE_PARTICIPATES_IN_PATHWAY Signaling by ALK fusions and activated point mutan... | {
"variant": "NM_000546.6(TP53):c.560-19_560-9del",
"pathway": "RET signaling"
} | 1 |
co_mech_00183 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_000051.4(ATM):c.6054_6056dup (p.Tyr2019Ter) affects the Cyclin A:Cdk2-associated events at S phase entry pathway, citing each molecular step. | NM_000051.4(ATM):c.6054_6056dup (p.Tyr2019Ter) VARIANT_IN_GENE ATM -> ATM GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Degradation -> AKT1 GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Degradation -> AKT1 GENE_PARTICIPATES_IN_PATHWAY Cyclin A:Cdk2-associated events at S phase entry | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000051.4(ATM):c.6054_6056dup (p.Tyr2019Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000051.4(ATM):c.6054_6056dup (p.Tyr2019Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_co... | NM_000051.4(ATM):c.6054_6056dup (p.Tyr2019Ter) VARIANT_IN_GENE ATM -> ATM GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Degradation -> AKT1 GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Degradation -> AKT1 GENE_PARTICIPATES_IN_PATHWAY Cyclin A:Cdk2-associated events at S phase entry | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ATM",
"source_db": "UniProt",
"payload": {
"accession": "Q13315",
"sequence": "MSLVLNDLLICCRQLEHDRATERKKEVEKFKRLIRDPETIKHLDRHSDSKQGKYLNWDAVFRFLQKYIQKETECLRIAKPNVSASTQASRQKKMQEISSLVKYFIKCANRRAPRLKCQELLNYIMDTVKDSSNGA... | [
{
"source_db": "ClinVar",
"source_id": "ATM",
"text": "NM_000051.4(ATM):c.6054_6056dup (p.Tyr2019Ter) VARIANT_IN_GENE ATM",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-6804757",
"text": "ATM GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Degradation",
"conf... | {
"variant": "NM_000051.4(ATM):c.6054_6056dup (p.Tyr2019Ter)",
"pathway": "Cyclin A:Cdk2-associated events at S phase entry"
} | 1 |
co_mech_00184 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000057.4(BLM):c.1795del (p.Arg599fs) affects the APC truncation mutants are not K63 polyubiquitinated pathway, citing each molecular step. | NM_000057.4(BLM):c.1795del (p.Arg599fs) VARIANT_IN_GENE BLM -> BLM GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> APC GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> APC GENE_PARTICIPATES_IN_PATHWAY APC truncation mutants are not K63 polyubiquitinated | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000057.4(BLM):c.1795del (p.Arg599fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000057.4(BLM):c.1795del (p.Arg599fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000057.4(BLM):c.1795del (p.Arg599fs) VARIANT_IN_GENE BLM -> BLM GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> APC GENE_ANNOTATED_WITH_GO_TERM DNA damage response -> APC GENE_PARTICIPATES_IN_PATHWAY APC truncation mutants are not K63 polyubiquitinated | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BLM",
"source_db": "UniProt",
"payload": {
"accession": "P54132",
"sequence": "MAAVPQNNLQEQLERHSARTLNNKLSLSKPKFSGFTFKKKTSSDNNVSVTNVSVAKTPVLRNKDVNVTEDFSFSEPLPNTTNQQRVKDFFKNAPAGQETQRGGSKSLLPDFLQTPKEVVCTTQNTPTVKKSRDTA... | [
{
"source_db": "ClinVar",
"source_id": "BLM",
"text": "NM_000057.4(BLM):c.1795del (p.Arg599fs) VARIANT_IN_GENE BLM",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0006974",
"text": "BLM GENE_ANNOTATED_WITH_GO_TERM DNA damage response",
"confidence": 0.6
},
{
"s... | {
"variant": "NM_000057.4(BLM):c.1795del (p.Arg599fs)",
"pathway": "APC truncation mutants are not K63 polyubiquitinated"
} | 0.774597 |
co_mech_00185 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_004984.4(KIF5A):c.737G>T (p.Gly246Val) affects the Defective Mismatch Repair Associated With MSH3 pathway, citing each molecular step. | NM_004984.4(KIF5A):c.737G>T (p.Gly246Val) VARIANT_IN_GENE KIF5A -> KIF5A GENE_ANNOTATED_WITH_GO_TERM ATP binding -> MSH2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> MSH2 GENE_PARTICIPATES_IN_PATHWAY Defective Mismatch Repair Associated With MSH3 | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004984.4(KIF5A):c.737G>T (p.Gly246Val)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004984.4(KIF5A):c.737G>T (p.Gly246Val)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_004984.4(KIF5A):c.737G>T (p.Gly246Val) VARIANT_IN_GENE KIF5A -> KIF5A GENE_ANNOTATED_WITH_GO_TERM ATP binding -> MSH2 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> MSH2 GENE_PARTICIPATES_IN_PATHWAY Defective Mismatch Repair Associated With MSH3 | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KIF5A",
"source_db": "UniProt",
"payload": {
"accession": "Q12840",
"sequence": "MAETNNECSIKVLCRFRPLNQAEILRGDKFIPIFQGDDSVVIGGKPYVFDRVFPPNTTQEQVYHACAMQIVKDVLAGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIARDIFNHIYSMDENLEFHIKV... | [
{
"source_db": "ClinVar",
"source_id": "KIF5A",
"text": "NM_004984.4(KIF5A):c.737G>T (p.Gly246Val) VARIANT_IN_GENE KIF5A",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0005524",
"text": "KIF5A GENE_ANNOTATED_WITH_GO_TERM ATP binding",
"confidence": 0.6
},
{
"s... | {
"variant": "NM_004984.4(KIF5A):c.737G>T (p.Gly246Val)",
"pathway": "Defective Mismatch Repair Associated With MSH3"
} | 0.774597 |
co_mech_00186 | mechanistic_explanation | coding_variant | hard | 3 | Explain the molecular mechanism by which NM_000038.6(APC):c.5387_5390del (p.Lys1796fs) affects the TCF dependent signaling in response to WNT pathway, citing each molecular step. | NM_000038.6(APC):c.5387_5390del (p.Lys1796fs) VARIANT_IN_GENE APC -> APC PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY TCF dependent signaling in response to WNT | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000038.6(APC):c.5387_5390del (p.Lys1796fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000038.6(APC):c.5387_5390del (p.Lys1796fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_conf... | NM_000038.6(APC):c.5387_5390del (p.Lys1796fs) VARIANT_IN_GENE APC -> APC PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1 -> CTNNB1 GENE_PARTICIPATES_IN_PATHWAY TCF dependent signaling in response to WNT | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "APC",
"source_db": "UniProt",
"payload": {
"accession": "P25054",
"sequence": "MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTKLETEASNMKEVLKQLQGSIEDEAMASSGQIDLLERLKELNLDSSNFPGVKLRSKMSLRSYGSREGSVSSRSGECSPVPMGSFPRRGFVNGSRESTGYLE... | [
{
"source_db": "ClinVar",
"source_id": "APC",
"text": "NM_000038.6(APC):c.5387_5390del (p.Lys1796fs) VARIANT_IN_GENE APC",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "CTNNB1",
"text": "APC PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH CTNNB1",
"confidence": 0.999
},
{
... | {
"variant": "NM_000038.6(APC):c.5387_5390del (p.Lys1796fs)",
"pathway": "TCF dependent signaling in response to WNT"
} | 0.999667 |
co_mech_00187 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000314.8(PTEN):c.428dup (p.Lys144fs) affects the Degradation of CDH1 pathway, citing each molecular step. | NM_000314.8(PTEN):c.428dup (p.Lys144fs) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Degradation of CDH1 | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000314.8(PTEN):c.428dup (p.Lys144fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000314.8(PTEN):c.428dup (p.Lys144fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
... | NM_000314.8(PTEN):c.428dup (p.Lys144fs) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration -> CDH1 GENE_PARTICIPATES_IN_PATHWAY Degradation of CDH1 | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PTEN",
"source_db": "UniProt",
"payload": {
"accession": "P60484",
"sequence": "MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVM... | [
{
"source_db": "ClinVar",
"source_id": "PTEN",
"text": "NM_000314.8(PTEN):c.428dup (p.Lys144fs) VARIANT_IN_GENE PTEN",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0030336",
"text": "PTEN GENE_ANNOTATED_WITH_GO_TERM negative regulation of cell migration",
"confidence"... | {
"variant": "NM_000314.8(PTEN):c.428dup (p.Lys144fs)",
"pathway": "Degradation of CDH1"
} | 0.774597 |
co_mech_00188 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_001042492.3(NF1):c.3691_3698dup (p.Cys1233fs) affects the Post-translational protein phosphorylation pathway, citing each molecular step. | NM_001042492.3(NF1):c.3691_3698dup (p.Cys1233fs) VARIANT_IN_GENE NF1 -> NF1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of endothelial cell proliferation -> APOE GENE_ANNOTATED_WITH_GO_TERM negative regulation of endothelial cell proliferation -> APOE GENE_PARTICIPATES_IN_PATHWAY Post-translational protein phosphor... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_001042492.3(NF1):c.3691_3698dup (p.Cys1233fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_001042492.3(NF1):c.3691_3698dup (p.Cys1233fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edg... | NM_001042492.3(NF1):c.3691_3698dup (p.Cys1233fs) VARIANT_IN_GENE NF1 -> NF1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of endothelial cell proliferation -> APOE GENE_ANNOTATED_WITH_GO_TERM negative regulation of endothelial cell proliferation -> APOE GENE_PARTICIPATES_IN_PATHWAY Post-translational protein phosphor... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "NF1",
"source_db": "UniProt",
"payload": {
"accession": "P21359",
"sequence": "MAAHRPVEWVQAVVSRFDEQLPIKTGQQNTHTKVSTEHNKECLINISKYKFSLVISGLTTILKNVNNMRIFGEAAEKNLYLSQLIILDTLEKCLAGQPKDTMRLDETMLVKQLLPEICHFLHTCREGNQHAAELR... | [
{
"source_db": "ClinVar",
"source_id": "NF1",
"text": "NM_001042492.3(NF1):c.3691_3698dup (p.Cys1233fs) VARIANT_IN_GENE NF1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0001937",
"text": "NF1 GENE_ANNOTATED_WITH_GO_TERM negative regulation of endothelial cell proliferat... | {
"variant": "NM_001042492.3(NF1):c.3691_3698dup (p.Cys1233fs)",
"pathway": "Post-translational protein phosphorylation"
} | 0.774597 |
co_mech_00189 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_007294.4(BRCA1):c.1009_1010del (p.Glu337fs) affects the Regulation of MECP2 expression and activity pathway, citing each molecular step. | NM_007294.4(BRCA1):c.1009_1010del (p.Glu337fs) VARIANT_IN_GENE BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> HTT PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> HTT GENE_PARTICIPATES_IN_PATHWAY Regulation of MECP2 expression and activity | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_007294.4(BRCA1):c.1009_1010del (p.Glu337fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_007294.4(BRCA1):c.1009_1010del (p.Glu337fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_co... | NM_007294.4(BRCA1):c.1009_1010del (p.Glu337fs) VARIANT_IN_GENE BRCA1 -> BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> HTT PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53 -> HTT GENE_PARTICIPATES_IN_PATHWAY Regulation of MECP2 expression and activity | null | [
"expression",
"intercell_role",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRCA1",
"source_db": "UniProt",
"payload": {
"accession": "P38398",
"sequence": "MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNR... | [
{
"source_db": "ClinVar",
"source_id": "BRCA1",
"text": "NM_007294.4(BRCA1):c.1009_1010del (p.Glu337fs) VARIANT_IN_GENE BRCA1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "TP53",
"text": "BRCA1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH TP53",
"confidence": 0.999
},
{... | {
"variant": "NM_007294.4(BRCA1):c.1009_1010del (p.Glu337fs)",
"pathway": "Regulation of MECP2 expression and activity"
} | 0.99925 |
co_mech_00190 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_203446.3(SYNJ1):c.2125C>T (p.Arg709Ter) affects the Constitutive Signaling by Overexpressed ERBB2 pathway, citing each molecular step. | NM_203446.3(SYNJ1):c.2125C>T (p.Arg709Ter) VARIANT_IN_GENE SYNJ1 -> SYNJ1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH GRB2 -> ERBB2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH GRB2 -> ERBB2 GENE_PARTICIPATES_IN_PATHWAY Constitutive Signaling by Overexpressed ERBB2 | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_203446.3(SYNJ1):c.2125C>T (p.Arg709Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_203446.3(SYNJ1):c.2125C>T (p.Arg709Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_203446.3(SYNJ1):c.2125C>T (p.Arg709Ter) VARIANT_IN_GENE SYNJ1 -> SYNJ1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH GRB2 -> ERBB2 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH GRB2 -> ERBB2 GENE_PARTICIPATES_IN_PATHWAY Constitutive Signaling by Overexpressed ERBB2 | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "SYNJ1",
"source_db": "UniProt",
"payload": {
"accession": "O43426",
"sequence": "MAFSKGFRIYHKLDPPPFSLIVETRHKEECLMFESGAVAVLSSAEKEAIKGTYSKVLDAYGLLGVLRLNLGDTMLHYLVLVTGCMSVGKIQESEVFRVTSTEFISLRIDSSDEDRISEVRKVLNSGNFYFAWS... | [
{
"source_db": "ClinVar",
"source_id": "SYNJ1",
"text": "NM_203446.3(SYNJ1):c.2125C>T (p.Arg709Ter) VARIANT_IN_GENE SYNJ1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "GRB2",
"text": "SYNJ1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH GRB2",
"confidence": 0.95
},
{
... | {
"variant": "NM_203446.3(SYNJ1):c.2125C>T (p.Arg709Ter)",
"pathway": "Constitutive Signaling by Overexpressed ERBB2"
} | 0.987012 |
co_mech_00191 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_006158.5(NEFL):c.1240dup (p.Gln414fs) affects the Processing of Capped Intron-Containing Pre-mRNA pathway, citing each molecular step. | NM_006158.5(NEFL):c.1240dup (p.Gln414fs) VARIANT_IN_GENE NEFL -> NEFL PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH SOD1 -> SOD1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FUS -> FUS GENE_PARTICIPATES_IN_PATHWAY Processing of Capped Intron-Containing Pre-mRNA | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_006158.5(NEFL):c.1240dup (p.Gln414fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_006158.5(NEFL):c.1240dup (p.Gln414fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1... | NM_006158.5(NEFL):c.1240dup (p.Gln414fs) VARIANT_IN_GENE NEFL -> NEFL PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH SOD1 -> SOD1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH FUS -> FUS GENE_PARTICIPATES_IN_PATHWAY Processing of Capped Intron-Containing Pre-mRNA | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "NEFL",
"source_db": "UniProt",
"payload": {
"accession": "P07196",
"sequence": "MSSFSYEPYYSTSYKRRYVETPRVHISSVRSGYSTARSAYSSYSAPVSSSLSVRRSYSSSSGSLMPSLENLDLSQVAAISNDLKSIRTQEKAQLQDLNDRFASFIERVHELEQQNKVLEAELLVLRQKHSEPSR... | [
{
"source_db": "ClinVar",
"source_id": "NEFL",
"text": "NM_006158.5(NEFL):c.1240dup (p.Gln414fs) VARIANT_IN_GENE NEFL",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "SOD1",
"text": "NEFL PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH SOD1",
"confidence": 0.976
},
{
"sou... | {
"variant": "NM_006158.5(NEFL):c.1240dup (p.Gln414fs)",
"pathway": "Processing of Capped Intron-Containing Pre-mRNA"
} | 0.991951 |
co_mech_00192 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_032043.3(BRIP1):c.918+1G>A affects the Negative regulation of FLT3 pathway, citing each molecular step. | NM_032043.3(BRIP1):c.918+1G>A VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_PARTICIPATES_IN_PATHWAY Negative regulation of FLT3 | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_032043.3(BRIP1):c.918+1G>A",
"source_node_type": "VARIANT",
"source_node_label": "NM_032043.3(BRIP1):c.918+1G>A",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source_d... | NM_032043.3(BRIP1):c.918+1G>A VARIANT_IN_GENE BRIP1 -> BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MLH1 -> MLH1 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_ANNOTATED_WITH_GO_TERM ATP binding -> FLT3 GENE_PARTICIPATES_IN_PATHWAY Negative regulation of FLT3 | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BRIP1",
"source_db": "UniProt",
"payload": {
"accession": "Q9BX63",
"sequence": "MSSMWSEYTIGGVKIYFPYKAYPSQLAMMNSILRGLNSKQHCLLESPTGSGKSLALLCSALAWQQSLSGKPADEGVSEKAEVQLSCCCACHSKDFTNNDMNQGTSRHFNYPSTPPSERNGTSSTCQDSPEKTT... | [
{
"source_db": "ClinVar",
"source_id": "BRIP1",
"text": "NM_032043.3(BRIP1):c.918+1G>A VARIANT_IN_GENE BRIP1",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "MLH1",
"text": "BRIP1 PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH MLH1",
"confidence": 0.999
},
{
"source_db":... | {
"variant": "NM_032043.3(BRIP1):c.918+1G>A",
"pathway": "Negative regulation of FLT3"
} | 0.81503 |
co_mech_00193 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_000465.4(BARD1):c.540_542del (p.Tyr180_Glu181delinsTer) affects the Erythropoietin activates STAT5 pathway, citing each molecular step. | NM_000465.4(BARD1):c.540_542del (p.Tyr180_Glu181delinsTer) VARIANT_IN_GENE BARD1 -> Single allele VARIANT_IN_GENE BARD1 -> Single allele VARIANT_IN_GENE LEPR -> LEPR PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH JAK2 -> JAK2 GENE_PARTICIPATES_IN_PATHWAY Erythropoietin activates STAT5 | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000465.4(BARD1):c.540_542del (p.Tyr180_Glu181delinsTer)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000465.4(BARD1):c.540_542del (p.Tyr180_Glu181delinsTer)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "... | NM_000465.4(BARD1):c.540_542del (p.Tyr180_Glu181delinsTer) VARIANT_IN_GENE BARD1 -> Single allele VARIANT_IN_GENE BARD1 -> Single allele VARIANT_IN_GENE LEPR -> LEPR PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH JAK2 -> JAK2 GENE_PARTICIPATES_IN_PATHWAY Erythropoietin activates STAT5 | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "BARD1",
"source_db": "UniProt",
"payload": {
"accession": "Q99728",
"sequence": "MPDNRQPRNRQPRIRSGNEPRSAPAMEPDGRGAWAHSRAALDRLEKLLRCSRCTNILREPVCLGGCEHIFCSNCVSDCIGTGCPVCYTPAWIQDLKINRQLDSMIQLCSKLRNLLHDNELSDLKEDKPRKSLF... | [
{
"source_db": "ClinVar",
"source_id": "BARD1",
"text": "NM_000465.4(BARD1):c.540_542del (p.Tyr180_Glu181delinsTer) VARIANT_IN_GENE BARD1",
"confidence": 1
},
{
"source_db": "ClinVar",
"source_id": "Single allele",
"text": "Single allele VARIANT_IN_GENE BARD1",
"confidence": 1
... | {
"variant": "NM_000465.4(BARD1):c.540_542del (p.Tyr180_Glu181delinsTer)",
"pathway": "Erythropoietin activates STAT5"
} | 0.9998 |
co_mech_00194 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000314.8(PTEN):c.730_745del (p.Pro244fs) affects the Pre-NOTCH Processing in the Endoplasmic Reticulum pathway, citing each molecular step. | NM_000314.8(PTEN):c.730_745del (p.Pro244fs) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM heart development -> NOTCH1 GENE_ANNOTATED_WITH_GO_TERM heart development -> NOTCH1 GENE_PARTICIPATES_IN_PATHWAY Pre-NOTCH Processing in the Endoplasmic Reticulum | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000314.8(PTEN):c.730_745del (p.Pro244fs)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000314.8(PTEN):c.730_745del (p.Pro244fs)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confiden... | NM_000314.8(PTEN):c.730_745del (p.Pro244fs) VARIANT_IN_GENE PTEN -> PTEN GENE_ANNOTATED_WITH_GO_TERM heart development -> NOTCH1 GENE_ANNOTATED_WITH_GO_TERM heart development -> NOTCH1 GENE_PARTICIPATES_IN_PATHWAY Pre-NOTCH Processing in the Endoplasmic Reticulum | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PTEN",
"source_db": "UniProt",
"payload": {
"accession": "P60484",
"sequence": "MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVM... | [
{
"source_db": "ClinVar",
"source_id": "PTEN",
"text": "NM_000314.8(PTEN):c.730_745del (p.Pro244fs) VARIANT_IN_GENE PTEN",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0007507",
"text": "PTEN GENE_ANNOTATED_WITH_GO_TERM heart development",
"confidence": 0.6
},
{
... | {
"variant": "NM_000314.8(PTEN):c.730_745del (p.Pro244fs)",
"pathway": "Pre-NOTCH Processing in the Endoplasmic Reticulum"
} | 0.774597 |
co_mech_00195 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which GRCh38/hg38 7p22.1(chr7:5448387-6276950)x1 affects the Signaling by ALK pathway, citing each molecular step. | GRCh38/hg38 7p22.1(chr7:5448387-6276950)x1 VARIANT_IN_GENE ACTB -> ACTB GENE_ANNOTATED_WITH_GO_TERM chromatin remodeling -> MYC GENE_ANNOTATED_WITH_GO_TERM chromatin remodeling -> MYC GENE_PARTICIPATES_IN_PATHWAY Signaling by ALK | {
"steps": [
{
"hop": 1,
"source_node_id": "GRCh38/hg38 7p22.1(chr7:5448387-6276950)x1",
"source_node_type": "VARIANT",
"source_node_label": "GRCh38/hg38 7p22.1(chr7:5448387-6276950)x1",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | GRCh38/hg38 7p22.1(chr7:5448387-6276950)x1 VARIANT_IN_GENE ACTB -> ACTB GENE_ANNOTATED_WITH_GO_TERM chromatin remodeling -> MYC GENE_ANNOTATED_WITH_GO_TERM chromatin remodeling -> MYC GENE_PARTICIPATES_IN_PATHWAY Signaling by ALK | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "ACTB",
"source_db": "UniProt",
"payload": {
"accession": "P60709",
"sequence": "MDDDIAALVVDNGSGMCKAGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQSKRGILTLKYPIEHGIVTNWDDMEKIWHHTFYNELRVAPEEHPVLLTEAPLNPKANREKMTQIMFETFNTPAMYV... | [
{
"source_db": "ClinVar",
"source_id": "ACTB",
"text": "GRCh38/hg38 7p22.1(chr7:5448387-6276950)x1 VARIANT_IN_GENE ACTB",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0006338",
"text": "ACTB GENE_ANNOTATED_WITH_GO_TERM chromatin remodeling",
"confidence": 0.6
},
{... | {
"variant": "GRCh38/hg38 7p22.1(chr7:5448387-6276950)x1",
"pathway": "Signaling by ALK"
} | 0.774597 |
co_mech_00196 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_003482.4(KMT2D):c.10625T>C (p.Leu3542Pro) affects the PI5P Regulates TP53 Acetylation pathway, citing each molecular step. | NM_003482.4(KMT2D):c.10625T>C (p.Leu3542Pro) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> TP53 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> TP53 GENE_PARTICIPATES_IN_PATHWAY PI5P Regulates TP53 Acetylation | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_003482.4(KMT2D):c.10625T>C (p.Leu3542Pro)",
"source_node_type": "VARIANT",
"source_node_label": "NM_003482.4(KMT2D):c.10625T>C (p.Leu3542Pro)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confid... | NM_003482.4(KMT2D):c.10625T>C (p.Leu3542Pro) VARIANT_IN_GENE KMT2D -> KMT2D GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> TP53 GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding -> TP53 GENE_PARTICIPATES_IN_PATHWAY PI5P Regulates TP53 Acetylation | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "KMT2D",
"source_db": "UniProt",
"payload": {
"accession": "O14686",
"sequence": "MDSQKLAGEDKDSEPAADGPAASEDPSATESDLPNPHVGEVSVLSSGSPRLQETPQDCSGGPVRRCALCNCGEPSLHGQRELRRFELPFDWPRCPVVSPGGSPGPNEAVLPSEDLSQIGFPEGLTPAHLGEPG... | [
{
"source_db": "ClinVar",
"source_id": "KMT2D",
"text": "NM_003482.4(KMT2D):c.10625T>C (p.Leu3542Pro) VARIANT_IN_GENE KMT2D",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0000976",
"text": "KMT2D GENE_ANNOTATED_WITH_GO_TERM transcription cis-regulatory region binding",
... | {
"variant": "NM_003482.4(KMT2D):c.10625T>C (p.Leu3542Pro)",
"pathway": "PI5P Regulates TP53 Acetylation"
} | 0.774597 |
co_mech_00197 | mechanistic_explanation | coding_variant | medium | 4 | Explain the molecular mechanism by which NM_004217.4(AURKB):c.847C>T (p.Arg283Cys) affects the SUMOylation of transcription factors pathway, citing each molecular step. | NM_004217.4(AURKB):c.847C>T (p.Arg283Cys) VARIANT_IN_GENE AURKB -> AURKB GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Activity through Phosphorylation -> TP53 GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Activity through Phosphorylation -> TP53 GENE_PARTICIPATES_IN_PATHWAY SUMOylation of transcription factors | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_004217.4(AURKB):c.847C>T (p.Arg283Cys)",
"source_node_type": "VARIANT",
"source_node_label": "NM_004217.4(AURKB):c.847C>T (p.Arg283Cys)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_004217.4(AURKB):c.847C>T (p.Arg283Cys) VARIANT_IN_GENE AURKB -> AURKB GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Activity through Phosphorylation -> TP53 GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Activity through Phosphorylation -> TP53 GENE_PARTICIPATES_IN_PATHWAY SUMOylation of transcription factors | null | [
"conservation",
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "evolutionary",
"tag": "conservation",
"anchor_node_id": "NM_004217.4(AURKB):c.847C>T (p.Arg283Cys)",
"source_db": "UCSC_phyloP",
"payload": {
"chrom": "chr17",
"pos": 8205230,
"track": "phyloP100way",
"window": 20,
"scores": [
-0.214015999999999... | [
{
"source_db": "ClinVar",
"source_id": "AURKB",
"text": "NM_004217.4(AURKB):c.847C>T (p.Arg283Cys) VARIANT_IN_GENE AURKB",
"confidence": 1
},
{
"source_db": "Reactome",
"source_id": "R-HSA-6804756",
"text": "AURKB GENE_PARTICIPATES_IN_PATHWAY Regulation of TP53 Activity through Phosp... | {
"variant": "NM_004217.4(AURKB):c.847C>T (p.Arg283Cys)",
"pathway": "SUMOylation of transcription factors"
} | 1 |
co_mech_00198 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_017617.5(NOTCH1):c.743-1G>T affects the Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex pathway, citing each molecular step. | NM_017617.5(NOTCH1):c.743-1G>T VARIANT_IN_GENE NOTCH1 -> NOTCH1 GENE_ANNOTATED_WITH_GO_TERM DNA-templated transcription -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM DNA-templated transcription -> CHEK2 GENE_PARTICIPATES_IN_PATHWAY Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_017617.5(NOTCH1):c.743-1G>T",
"source_node_type": "VARIANT",
"source_node_label": "NM_017617.5(NOTCH1):c.743-1G>T",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence": 1,
"edge_source... | NM_017617.5(NOTCH1):c.743-1G>T VARIANT_IN_GENE NOTCH1 -> NOTCH1 GENE_ANNOTATED_WITH_GO_TERM DNA-templated transcription -> CHEK2 GENE_ANNOTATED_WITH_GO_TERM DNA-templated transcription -> CHEK2 GENE_PARTICIPATES_IN_PATHWAY Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "NOTCH1",
"source_db": "UniProt",
"payload": {
"accession": "P46531",
"sequence": "MPPLLAPLLCLALLPALAARGPRCSQPGETCLNGGKCEAANGTEACVCGGAFVGPRCQDPNPCLSTPCKNAGTCHVVDRRGVADYACSCALGFSGPLCLTPLDNACLTNPCRNGGTCDLLTLTEYKCRCPPG... | [
{
"source_db": "ClinVar",
"source_id": "NOTCH1",
"text": "NM_017617.5(NOTCH1):c.743-1G>T VARIANT_IN_GENE NOTCH1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0006351",
"text": "NOTCH1 GENE_ANNOTATED_WITH_GO_TERM DNA-templated transcription",
"confidence": 0.6
},
... | {
"variant": "NM_017617.5(NOTCH1):c.743-1G>T",
"pathway": "Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex"
} | 0.774597 |
co_mech_00199 | mechanistic_explanation | coding_variant | hard | 5 | Explain the molecular mechanism by which NM_058216.3(RAD51C):c.829A>T (p.Arg277Ter) affects the Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells pathway, citing each molecular step. | NM_058216.3(RAD51C):c.829A>T (p.Arg277Ter) VARIANT_IN_GENE RAD51C -> RAD51C PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CREBBP GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CREBBP GENE_PARTICIPA... | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_058216.3(RAD51C):c.829A>T (p.Arg277Ter)",
"source_node_type": "VARIANT",
"source_node_label": "NM_058216.3(RAD51C):c.829A>T (p.Arg277Ter)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence... | NM_058216.3(RAD51C):c.829A>T (p.Arg277Ter) VARIANT_IN_GENE RAD51C -> RAD51C PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2 -> BRCA2 GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CREBBP GENE_ANNOTATED_WITH_GO_TERM positive regulation of DNA-templated transcription -> CREBBP GENE_PARTICIPA... | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "RAD51C",
"source_db": "UniProt",
"payload": {
"accession": "O43502",
"sequence": "MRGKTFRFEMQRDLVSFPLSPAVRVKLVSAGFQTAEELLEVKPSELSKEVGISKAEALETLQIIRRECLTNKPRYAGTSESHKKCTALELLEQEHTQGFIITFCSALDDILGGGVPLMKTTEICGAPGVGKT... | [
{
"source_db": "ClinVar",
"source_id": "RAD51C",
"text": "NM_058216.3(RAD51C):c.829A>T (p.Arg277Ter) VARIANT_IN_GENE RAD51C",
"confidence": 1
},
{
"source_db": "STRING",
"source_id": "BRCA2",
"text": "RAD51C PROTEIN_FUNCTIONALLY_ASSOCIATED_WITH BRCA2",
"confidence": 0.999
},
... | {
"variant": "NM_058216.3(RAD51C):c.829A>T (p.Arg277Ter)",
"pathway": "Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells"
} | 0.81503 |
co_mech_00200 | mechanistic_explanation | coding_variant | hard | 4 | Explain the molecular mechanism by which NM_000021.4(PSEN1):c.548G>T (p.Gly183Val) affects the NIK-->noncanonical NF-kB signaling pathway, citing each molecular step. | NM_000021.4(PSEN1):c.548G>T (p.Gly183Val) VARIANT_IN_GENE PSEN1 -> PSEN1 GENE_ANNOTATED_WITH_GO_TERM endopeptidase activity -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM endopeptidase activity -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY NIK-->noncanonical NF-kB signaling | {
"steps": [
{
"hop": 1,
"source_node_id": "NM_000021.4(PSEN1):c.548G>T (p.Gly183Val)",
"source_node_type": "VARIANT",
"source_node_label": "NM_000021.4(PSEN1):c.548G>T (p.Gly183Val)",
"edge_relation": "VARIANT_IN_GENE",
"edge_evidence_type": "curated",
"edge_confidence":... | NM_000021.4(PSEN1):c.548G>T (p.Gly183Val) VARIANT_IN_GENE PSEN1 -> PSEN1 GENE_ANNOTATED_WITH_GO_TERM endopeptidase activity -> PSMA6 GENE_ANNOTATED_WITH_GO_TERM endopeptidase activity -> PSMA6 GENE_PARTICIPATES_IN_PATHWAY NIK-->noncanonical NF-kB signaling | null | [
"expression",
"protein_sequence",
"protein_structure"
] | [
{
"family": "sequence",
"tag": "protein_sequence",
"anchor_node_id": "PSEN1",
"source_db": "UniProt",
"payload": {
"accession": "P49768",
"sequence": "MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSRQVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVGQRALHSI... | [
{
"source_db": "ClinVar",
"source_id": "PSEN1",
"text": "NM_000021.4(PSEN1):c.548G>T (p.Gly183Val) VARIANT_IN_GENE PSEN1",
"confidence": 1
},
{
"source_db": "GO",
"source_id": "GO:0004175",
"text": "PSEN1 GENE_ANNOTATED_WITH_GO_TERM endopeptidase activity",
"confidence": 0.6
},... | {
"variant": "NM_000021.4(PSEN1):c.548G>T (p.Gly183Val)",
"pathway": "NIK-->noncanonical NF-kB signaling"
} | 0.774597 |
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