{"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"}],"hgnc":"HGNC:7882","ensembl":"ENSG00000134250","uniprot":"Q04721","entrez":"4853","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":"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/"}]}}