{"entity":{"id":"notch2","kind":"target","name":"NOTCH2","aka":["notch receptor 2","Neurogenic locus notch homolog protein 2"],"tldr":"NOTCH2 (Neurogenic locus notch homolog protein 2) 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 Non-Hodgkin lymphoma, Breast cancer, Lung cancer 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 2 clinical evidence items and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.78 (direct and indirect evidence; datatypes clinical 0.16, affected pathway 0.83, literature 0.98, genetic association 0.38, somatic mutation 0.96, animal model 0.54). IntOGen calls it a driver in 19 cohorts (6 activating, 13 loss-of-function), covering Adenoid Cystic Carcinoma, Acute Myeloid Leukaemia, Basal Cell Carcinoma, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Cutaneous Squamous Cell Carcinoma and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:7882","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7882"},{"label":"UniProt Q04721","url":"https://www.uniprot.org/uniprotkb/Q04721/entry"},{"label":"NCBI Gene 4853","url":"https://www.ncbi.nlm.nih.gov/gene/4853"},{"label":"Ensembl ENSG00000134250","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000134250"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["non-hodgkin-lymphoma","breast-cancer","lung-cancer","head-and-neck","prostate","skin-cancer","salivary-gland","urothelial"],"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: Open Targets known-drug datatype score 0.16; IntOGen calls it an activating (Act) driver in 6 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 13 cohorts; 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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"NOTCH2","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:7882","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7882","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q04721","url":"https://www.uniprot.org/uniprotkb/Q04721/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene NOTCH2","url":"https://civicdb.org/features/3935","note":"2 evidence items, 0 assertions, 1 variants; diseases: Mantle Cell Lymphoma, Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000134250","url":"https://platform.opentargets.org/target/ENSG00000134250/associations","note":"association with cancer (MONDO_0004992) 0.78; per-cancer scores at or above 0.5: colorectal cancer 0.52, gastric cancer 0.51, prostate cancer 0.54, ovarian cancer 0.54, melanoma 0.58, neuroendocrine neoplasm 0.51 (GraphQL API, CC0)"},{"label":"IntOGen NOTCH2","url":"https://www.intogen.org/search?gene=NOTCH2","note":"driver in 19 cohorts (Act 6, LoF 13); 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 NOTCH2: RNA low tissue specificity; no normal tissue stained high. Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Breast cancer (all types), Lung cancer (all types), Head and neck squamous cell carcinoma, Prostate cancer, Skin cancer (all types), Salivary gland cancers and more); Open Targets associates it with 1 specific cancer type at or above 0.5 (diffuse large B-cell lymphoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt Q04721","url":"https://www.uniprot.org/uniprotkb/Q04721/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene NOTCH2","url":"https://civicdb.org/features/3935","note":"2 evidence items, 0 assertions, 1 variants; diseases: Mantle Cell Lymphoma, Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen NOTCH2","url":"https://www.intogen.org/search?gene=NOTCH2","note":"driver in 19 cohorts (Act 6, LoF 13); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas NOTCH2 tissue","url":"https://www.proteinatlas.org/ENSG00000134250-NOTCH2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000134250 associations","url":"https://platform.opentargets.org/target/ENSG00000134250/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7882","ensembl":"ENSG00000134250","uniprot":"Q04721","entrez":"4853","firstDescribed":1992,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Stifani et al, Nat. Genet, 1992, \"Human homologs of a Drosophila enhancer of split gene product define a novel family of nuclear proteins\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1303260/","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 bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation. Positively regulates self-renewal of liver cancer cells. Location: Cell membrane; Nucleus; Cytoplasm (UniProt). Locus 1p12 (HGNC).","whereFound":["Non-Hodgkin lymphoma: Open Targets association 0.68 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM, NHL)","Breast cancer: Open Targets association 0.65 with breast cancer (MONDO_0007254); IntOGen driver in 1 cohort (BRCA)","Lung cancer: Open Targets association 0.61 with lung cancer (MONDO_0008903)","Head and neck squamous cell carcinoma: IntOGen driver in 3 cohorts (HNSC)","Prostate cancer: Open Targets association 0.54 with prostate cancer (MONDO_0008315); IntOGen driver in 2 cohorts (PRAD)","Skin cancer: Open Targets association 0.58 with skin cancer (MONDO_0002898)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/notch2/","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":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"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":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"term":[{"id":"lymphoma-bio-lymphgen","kind":"term","name":"LymphGen and the genetic clusters of large B-cell lymphoma","route":"/terms/lymphoma-bio-lymphgen/"},{"id":"cyclin-d1-t11-14","kind":"term","name":"t(11;14), cyclin D1 and SOX11","route":"/terms/cyclin-d1-t11-14/"}],"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-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-chapuy-molecular-subtypes-dlbcl-nat-med-2018","kind":"paper","name":"Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes","route":"/key-papers/paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018/"}],"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/"}]}}