{"entity":{"id":"notch3","kind":"target","name":"NOTCH3","aka":["notch receptor 3","Neurogenic locus notch homolog protein 3","CASIL","CADASIL"],"tldr":"NOTCH3 (Neurogenic locus notch homolog protein 3) is a protein that switches other genes on and off. The public catalogues list it as a drug target and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Pancreatic ductal adenocarcinoma.","summary":"Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD), it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs.\n\nCIViC holds 2 clinical evidence items and 0 assertions across 1 variant, naming Tarextumab.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:7883","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7883"},{"label":"UniProt Q9UM47","url":"https://www.uniprot.org/uniprotkb/Q9UM47/entry"},{"label":"NCBI Gene 4854","url":"https://www.ncbi.nlm.nih.gov/gene/4854"},{"label":"Ensembl ENSG00000074181","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000074181"}],"tags":["cancer-genes-wave"],"related":["civic"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 1 therapies; CIViC holds 2 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Rectum Cancer."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"NOTCH3","role":["drug-target","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:7883","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7883","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9UM47","url":"https://www.uniprot.org/uniprotkb/Q9UM47/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene NOTCH3","url":"https://civicdb.org/features/3936","note":"2 evidence items, 0 assertions, 1 variants; diseases: Pancreatic Cancer, Rectum Cancer (GraphQL API, CC0)"}],"distribution":"one-type","specificityNote":"Specificity not established: no corpus medicine is aimed at it and the catalogues give it only the roles drug-target, biomarker; HPA finds the RNA tissue enhanced, which says where the protein sits but not whether the tumour differs from normal tissue. HPA NOTCH3: RNA tissue enhanced (blood vessel 201 nTPM); high antibody staining in 3 normal tissues; highest cancer staining carcinoid (2 of 4 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Pancreatic ductal adenocarcinoma); Open Targets associates it with 1 specific cancer type at or above 0.5 (myofibromatosis, infantile, 2). (No rule of scripts/fetch-target-specificity.ts fired.)","specificitySources":[{"label":"Human Protein Atlas NOTCH3 tissue","url":"https://www.proteinatlas.org/ENSG00000074181-NOTCH3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000074181 associations","url":"https://platform.opentargets.org/target/ENSG00000074181/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7883","ensembl":"ENSG00000074181","uniprot":"Q9UM47","entrez":"4854","firstDescribed":1996,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Joutel et al, Nature, 1996, \"Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8878478/","biology":"Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD), it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Location: Cell membrane; Nucleus (UniProt). Locus 19p13.12 (HGNC).","whereFound":["Pancreatic ductal adenocarcinoma: CIViC evidence names this disease"],"targetClass":"transcription","prevalence":[]},"route":"/targets/notch3/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"}],"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}]}}