NOTCH2
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination.
- 3 · How drugs use it
No product in this corpus aims at NOTCH2 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Sources: HGNC HGNC:7882 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q04721 (protein name, function text, keywords and locations (REST API)); CIViC gene NOTCH2 (2 evidence items, 0 assertions, 1 variants; diseases: Mantle Cell Lymphoma, Diffuse Large B-cell Lymphoma (GraphQL API, CC0)); Open Targets ENSG00000134250 (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)); IntOGen NOTCH2 (driver in 19 cohorts (Act 6, LoF 13); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- 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
top- 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.
Latest papers
topQuery for this target: (TITLE:"NOTCH2" OR ABSTRACT:"NOTCH2" OR TITLE:"notch receptor 2" OR ABSTRACT:"notch receptor 2" OR TITLE:"Neurogenic locus notch homolog protein 2" OR ABSTRACT:"Neurogenic locus notch homolog protein 2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about NOTCH2, not a curated reading list.
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