NOTCH1
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.
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 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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 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 NOTCH1 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:7881 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P46531 (protein name, function text, keywords and locations (REST API)); CIViC gene NOTCH1 (33 evidence items, 0 assertions, 33 variants; diseases: T-cell Acute Lymphoblastic Leukaemia, Chronic Lymphocytic Leukaemia, Lung Non-small Cell Carcinoma, Mantle Cell Lymphoma, Colorectal Cancer and 3 more (GraphQL API, CC0)); Open Targets ENSG00000148400 (association with cancer (MONDO_0004992) 0.85; per-cancer scores at or above 0.5: oesophageal cancer 0.56, cervical cancer 0.53, head and neck squamous cell carcinoma 0.69, acute lymphoblastic leukaemia 0.79, B-cell chronic lymphocytic leukaemia 0.74, non-Hodgkin lymphoma 0.81 (GraphQL API, CC0)); IntOGen NOTCH1 (driver in 39 cohorts (Act 10, LoF 29); 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 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).
- 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)
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 0.08; 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.
Latest papers
topQuery for this target: (TITLE:"NOTCH1" OR ABSTRACT:"NOTCH1" OR TITLE:"notch receptor 1" OR ABSTRACT:"notch receptor 1" OR TITLE:"Neurogenic locus notch homolog protein 1" OR ABSTRACT:"Neurogenic locus notch homolog protein 1" OR TITLE:"TAN1" OR ABSTRACT:"TAN1") 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 NOTCH1, not a curated reading list.
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