# NOTCH2

Source: https://onco.cc/targets/notch2/  
OnCo record `notch2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: notch receptor 2; Neurogenic locus notch homolog protein 2
- Tags: cancer-genes-wave
- Symbol: NOTCH2
- 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 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).
- Where found: 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)

## 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.

## Sources

- HGNC HGNC:7882: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7882
- UniProt Q04721: https://www.uniprot.org/uniprotkb/Q04721/entry
- NCBI Gene 4853: https://www.ncbi.nlm.nih.gov/gene/4853
- Ensembl ENSG00000134250: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000134250

## 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: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Salivary gland cancers](https://onco.cc/cancers/salivary-gland/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)

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JSON: https://onco.cc/api/v1/entities/notch2.json