{"entity":{"id":"notch1","kind":"target","name":"NOTCH1","aka":["notch receptor 1","Neurogenic locus notch homolog protein 1","TAN1"],"tldr":"NOTCH1 (Neurogenic locus notch homolog protein 1) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Leukaemia, Non-Hodgkin lymphoma, Head and neck squamous cell carcinoma and 5 more.","summary":"Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) 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 33 clinical evidence items and 0 assertions across 33 variants, naming Prednisone, Porcupine Inhibitor WNT974, Nirogacestat and NOTCH1 Antibody (PF-06293622) and others. Open Targets scores its association with cancer at 0.85 (direct and indirect evidence; datatypes clinical 0.08, affected pathway 0.97, literature 1.00, genetic association 0.00, somatic mutation 0.95, animal model 0.43). IntOGen calls it a driver in 39 cohorts (10 activating, 29 loss-of-function), covering Acute Lymphoblastic Leukaemia, Angiosarcoma, Basal Cell Carcinoma, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Cervical Squamous Cell Carcinoma and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:7881","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7881"},{"label":"UniProt P46531","url":"https://www.uniprot.org/uniprotkb/P46531/entry"},{"label":"NCBI Gene 4851","url":"https://www.ncbi.nlm.nih.gov/gene/4851"},{"label":"Ensembl ENSG00000148400","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000148400"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["leukaemia","non-hodgkin-lymphoma","head-and-neck","lung-cancer","esophageal","salivary-gland","colorectal","cervical","tnbc","sclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["field-cancerisation","notch"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-stoeck-notch-rearrangements-tnbc-cancer-discov-2014","paper-wang-notch-pest-mutations-tnbc-ccr-2015","paper-george-sclc-genomic-profiles-nature-2015"],"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: Open Targets known-drug datatype score 0.08; IntOGen calls it an activating (Act) driver in 10 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 29 cohorts; CIViC holds 33 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: T-cell Acute Lymphoblastic Leukaemia; Adult T-cell Leukaemia/lymphoma; Low-Grade Glioma, NOS.","Triple-negative breast cancer: activating NOTCH1/NOTCH2 rearrangements in 6 of 66 TNBCs and no other solid tumour (Stoeck 2014); PEST-domain mutations of NOTCH1 to 3 enriched in TNBC and sensitive to gamma-secretase inhibition in xenografts (Wang 2015); NOTCH1 mutation 5% of METABRIC and MSK triple-negative samples (cBioPortal).","Lung cancer: a tumour suppressor in both squamous and small-cell disease, the opposite of its role in T-cell leukaemia. Truncating mutations in 7.9% of squamous tumours (cBioPortal), and NOTCH family inactivation in 25% of small-cell cancers, where switching NOTCH back on in mice reduced tumour number and abolished the neuroendocrine programme (George 2015)."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"NOTCH1","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:7881","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7881","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P46531","url":"https://www.uniprot.org/uniprotkb/P46531/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene NOTCH1","url":"https://civicdb.org/features/50","note":"33 evidence items, 0 assertions, 33 variants; diseases: T-cell Acute Lymphoblastic Leukaemia, Chronic Lymphocytic Leukaemia, Lung Non-small Cell Carcinoma, Mantle Cell Lymphoma, Colorectal Cancer and 3 more (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000148400","url":"https://platform.opentargets.org/target/ENSG00000148400/associations","note":"association with cancer (MONDO_0004992) 0.85; per-cancer scores at or above 0.5: oesophageal cancer 0.56, cervical cancer 0.53, head and neck squamous cell carcinoma 0.69, acute lymphoblastic leukaemia 0.79, B-cell chronic lymphocytic leukaemia 0.74, non-Hodgkin lymphoma 0.81 (GraphQL API, CC0)"},{"label":"IntOGen NOTCH1","url":"https://www.intogen.org/search?gene=NOTCH1","note":"driver in 39 cohorts (Act 10, LoF 29); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA NOTCH1: RNA low tissue specificity; high antibody staining in 8 normal tissues; highest cancer staining colorectal cancer (12 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Leukaemia, Lymphoma, Head and neck squamous cell carcinoma, Lung cancer (all types), Oesophageal cancer, Salivary gland cancers, Colorectal cancer and more); Open Targets associates it with 4 specific cancer types at or above 0.5 (B-cell chronic lymphocytic leukemia, head and neck squamous cell carcinoma, lymphoid leukemia, squamous cell lung carcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P46531","url":"https://www.uniprot.org/uniprotkb/P46531/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene NOTCH1","url":"https://civicdb.org/features/50","note":"33 evidence items, 0 assertions, 33 variants; diseases: T-cell Acute Lymphoblastic Leukaemia, Chronic Lymphocytic Leukaemia, Lung Non-small Cell Carcinoma, Mantle Cell Lymphoma, Colorectal Cancer and 3 more (GraphQL API, CC0)"},{"label":"IntOGen NOTCH1","url":"https://www.intogen.org/search?gene=NOTCH1","note":"driver in 39 cohorts (Act 10, LoF 29); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas NOTCH1 tissue","url":"https://www.proteinatlas.org/ENSG00000148400-NOTCH1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000148400 associations","url":"https://platform.opentargets.org/target/ENSG00000148400/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7881","ensembl":"ENSG00000148400","uniprot":"P46531","entrez":"4851","firstDescribed":1991,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Ellisen L.W. et al, Cell, 1991, \"TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1831692/","biology":"Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) 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. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. Location: Cell membrane; Late endosome membrane; Nucleus (UniProt). Locus 9q34.3 (HGNC).","whereFound":["Leukaemia: Open Targets association 0.82 with leukaemia (MONDO_0005059)","Non-Hodgkin lymphoma: Open Targets association 0.81 with non-Hodgkin lymphoma (MONDO_0018908)","Head and neck squamous cell carcinoma: Open Targets association 0.69 with head and neck squamous cell carcinoma (MONDO_0010150); CIViC evidence names this disease","Lung cancer: Open Targets association 0.66 with lung cancer (MONDO_0008903)","Oesophageal cancer: Open Targets association 0.56 with oesophageal cancer (MONDO_0007576); IntOGen driver in 3 cohorts (ESCA)","Salivary gland cancers: IntOGen driver in 3 cohorts (SACA)","Triple-negative breast cancer: activating rearrangement, pest-domain mutation or amplification 5-9%","Small-cell lung cancer: inactivating mutation 13-25%"],"targetClass":"transcription","prevalence":[{"cancerId":"tnbc","pct":"5-9","measure":"Activating rearrangement, PEST-domain mutation or amplification","source":"https://doi.org/10.1158/2159-8290.CD-13-0830","note":"NOTCH1 and NOTCH2 rearrangements causing constitutive activation in 6 of 66 TNBCs, 9%, and in no other solid tumour type (Stoeck 2014); PEST-domain mutations of NOTCH1, NOTCH2 and NOTCH3 and focal NOTCH2/NOTCH3 amplifications significantly enriched in the TNBC subset of TCGA (Wang 2015); cBioPortal: NOTCH1 mutation in 16 of 299, 5.4%, in brca_metabric and 9 of 176, 5.1%, in breast_msk_2018; NOTCH2 amplification in 21 of 119, 17.6%, in brca_tcga_pan_can_atlas_2018."},{"cancerId":"sclc","pct":"13-25","measure":"Inactivating mutation","source":"https://www.cbioportal.org/study/summary?id=sclc_ucologne_2015","note":"cBioPortal: NOTCH1 mutated in 16 of 120, 13.3%, in sclc_ucologne_2015. Inactivating mutations across the NOTCH family were found in 25% of the sequenced tumours, and activating Notch signalling in a mouse model strikingly reduced tumour number, extended survival and abolished neuroendocrine gene expression (George 2015)."}]},"route":"/targets/notch1/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"richter-transformation-cll","kind":"cancer","name":"Richter transformation of chronic lymphocytic leukaemia","route":"/cancers/richter-transformation-cll/"},{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"pathway":[{"id":"field-cancerisation","kind":"pathway","name":"Field cancerisation","route":"/pathways/field-cancerisation/"},{"id":"notch","kind":"pathway","name":"Notch signalling","route":"/pathways/notch/"}],"paper":[{"id":"paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020","kind":"paper","name":"A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications","route":"/key-papers/paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020/"},{"id":"paper-tcga-lung-squamous-nature-2012","kind":"paper","name":"Comprehensive genomic characterization of squamous cell lung cancers","route":"/key-papers/paper-tcga-lung-squamous-nature-2012/"},{"id":"paper-george-sclc-genomic-profiles-nature-2015","kind":"paper","name":"Comprehensive genomic profiles of small cell lung cancer","route":"/key-papers/paper-george-sclc-genomic-profiles-nature-2015/"},{"id":"paper-stoeck-notch-rearrangements-tnbc-cancer-discov-2014","kind":"paper","name":"Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma","route":"/key-papers/paper-stoeck-notch-rearrangements-tnbc-cancer-discov-2014/"},{"id":"paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018","kind":"paper","name":"Genetics and pathogenesis of diffuse large B-cell lymphoma","route":"/key-papers/paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018/"},{"id":"paper-wang-notch-pest-mutations-tnbc-ccr-2015","kind":"paper","name":"PEST domain mutations in Notch receptors comprise an oncogenic driver segment in triple-negative breast cancer sensitive to a gamma-secretase inhibitor","route":"/key-papers/paper-wang-notch-pest-mutations-tnbc-ccr-2015/"},{"id":"paper-erices-chilean-gallbladder-landscape-front-oncol-2025","kind":"paper","name":"The mutational landscape and actionable targets of gallbladder cancer: an ancestry-informed and comparative analysis of a Chilean population","route":"/key-papers/paper-erices-chilean-gallbladder-landscape-front-oncol-2025/"}],"term":[{"id":"lymphoma-bio-lymphgen","kind":"term","name":"LymphGen and the genetic clusters of large B-cell lymphoma","route":"/terms/lymphoma-bio-lymphgen/"}],"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}]}}