# NOTCH1

Source: https://onco.cc/targets/notch1/  
OnCo record `notch1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: notch receptor 1; Neurogenic locus notch homolog protein 1; TAN1
- Tags: cancer-genes-wave
- Symbol: NOTCH1
- Class: transcription
- 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).
- Where found: 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%

## 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).

## Sources

- HGNC HGNC:7881: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7881
- UniProt P46531: https://www.uniprot.org/uniprotkb/P46531/entry
- NCBI Gene 4851: https://www.ncbi.nlm.nih.gov/gene/4851
- Ensembl ENSG00000148400: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000148400

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Cervical cancer](https://onco.cc/cancers/cervical/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Richter transformation of chronic lymphocytic leukaemia](https://onco.cc/cancers/richter-transformation-cll/), [Salivary gland cancers](https://onco.cc/cancers/salivary-gland/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- pathways: [Field cancerisation](https://onco.cc/pathways/field-cancerisation/), [Notch signalling](https://onco.cc/pathways/notch/)
- key papers: [A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications](https://onco.cc/key-papers/paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020/), [Comprehensive genomic characterization of squamous cell lung cancers](https://onco.cc/key-papers/paper-tcga-lung-squamous-nature-2012/), [Comprehensive genomic profiles of small cell lung cancer](https://onco.cc/key-papers/paper-george-sclc-genomic-profiles-nature-2015/), [Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma](https://onco.cc/key-papers/paper-stoeck-notch-rearrangements-tnbc-cancer-discov-2014/), [Genetics and pathogenesis of diffuse large B-cell lymphoma](https://onco.cc/key-papers/paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018/), [PEST domain mutations in Notch receptors comprise an oncogenic driver segment in triple-negative breast cancer sensitive to a gamma-secretase inhibitor](https://onco.cc/key-papers/paper-wang-notch-pest-mutations-tnbc-ccr-2015/), [The mutational landscape and actionable targets of gallbladder cancer: an ancestry-informed and comparative analysis of a Chilean population](https://onco.cc/key-papers/paper-erices-chilean-gallbladder-landscape-front-oncol-2025/)
- terms: [LymphGen and the genetic clusters of large B-cell lymphoma](https://onco.cc/terms/lymphoma-bio-lymphgen/)
- roadmaps: [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](https://onco.cc/roadmaps/lymphoma-roadmap/)

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JSON: https://onco.cc/api/v1/entities/notch1.json