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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.
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.
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.
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.
Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination.
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.
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.)
Sources: UniProt Q04721; CIViC gene NOTCH2; IntOGen NOTCH2; Human Protein Atlas NOTCH2 tissue; Open Targets ENSG00000134250 associations
First described 1992. 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". Source.
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)
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).
RNA: low tissue specificity, detected in all normal tissues.
No normal tissue stained high; medium in Adrenal gland, Breast, Bronchus, Cerebellum, Cerebral cortex, Cervix and more.
No cancer stained high; medium in breast cancer, carcinoid, cervical cancer, colorectal cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
The piece that turns a research classification into something a trial can use on one person's biopsy, with a probability attached rather than a flat label. It is the reason genetics-directed lymphoma trials became possible at all.
The genetic nosology that precision-medicine trials in diffuse large B-cell lymphoma now use to pick patients. It gives a mechanism, not just a label: two of the four subtypes point at a drug class that already exists.
One of the two foundational genetic classifications of diffuse large B-cell lymphoma. Neither has yet changed what a patient receives outside a trial, but together they are the reason precision-medicine trials in this disease now select by genetics rather than by cell of origin.
Query 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.
Shares LymphGen and the genetic clusters of large B-cell lymphoma, A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications, Genetics and pathogenesis of diffuse large B-cell lymphoma, Salivary gland cancers.
Shares Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes, LymphGen and the genetic clusters of large B-cell lymphoma, A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications, Genetics and pathogenesis of diffuse large B-cell lymphoma.
Shares Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes, LymphGen and the genetic clusters of large B-cell lymphoma, A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications, Genetics and pathogenesis of diffuse large B-cell lymphoma.
Shares Salivary gland cancers, Skin cancer (all types), CIViC, IntOGen.
Shares Salivary gland cancers, Skin cancer (all types), Bladder & urothelial cancer, IntOGen.
Shares t(11;14), cyclin D1 and SOX11, Mantle cell lymphoma, 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, Skin cancer (all types).
Shares Salivary gland cancers, CIViC, IntOGen, Lung cancer (all types).
Shares Marginal zone lymphoma, Mantle cell lymphoma, Skin cancer (all types), CIViC.