RB1
RB1 (Retinoblastoma-associated protein) 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 Bladder & urothelial cancer, Lung cancer, Neuroendocrine tumours and 5 more.
Overview
Tumour suppressor that is a key regulator of the G1/S transition of the cell cycle. The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes. Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription.
CIViC holds 18 clinical evidence items and 0 assertions across 9 variants, naming Palbociclib, Fulvestrant, Gemcitabine and Olaparib and others. Open Targets scores its association with cancer at 0.93 (direct and indirect evidence; datatypes genetic literature 0.92, affected pathway 0.92, literature 1.00, genetic association 0.95, somatic mutation 0.98, animal model 0.68). IntOGen calls it a driver in 65 cohorts (1 activating, 61 loss-of-function), covering Adrenocortical Carcinoma, Bladder/Urinary Tract, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Cervical Squamous Cell Carcinoma, Oesophageal Adenocarcinoma 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 · RB1 (Retinoblastoma-associated protein) 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 Bladder & urothelial cancer, Lung cancer, Neuroendocrine tumours and 5 more.
- 1 · What it is
RB1 (Retinoblastoma-associated protein) 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 Bladder & urothelial cancer, Lung cancer, Neuroendocrine tumours and 5 more.
- 2 · What goes wrong in cancer
Tumour suppressor that is a key regulator of the G1/S transition of the cell cycle. The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes.
- 3 · How drugs use it
No product in this corpus aims at RB1 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:9884 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P06400 (protein name, function text, keywords and locations (REST API)); CIViC gene RB1 (18 evidence items, 0 assertions, 9 variants; diseases: Breast Cancer, Triple-negative Breast Cancer, Lung Non-small Cell Carcinoma, Glioblastoma, Oestrogen Receptor-positive Breast Cancer and 6 more (GraphQL API, CC0)); Open Targets ENSG00000139687 (association with cancer (MONDO_0004992) 0.93; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.70, small cell lung carcinoma 0.73, colorectal cancer 0.53, oesophageal cancer 0.55, hepatocellular carcinoma 0.63, prostate cancer 0.58 (GraphQL API, CC0)); IntOGen RB1 (driver in 65 cohorts (Act 1, LoF 61); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Tumour suppressor that is a key regulator of the G1/S transition of the cell cycle. The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes. Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription. Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase. RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilising histone methylation. Location: Nucleus; Cytoplasm (UniProt). Locus 13q14.2 (HGNC).
- Bladder & urothelial cancer: Open Targets association 0.80 with urinary bladder cancer (MONDO_0001187); IntOGen driver in 8 cohorts (BLADDER, BLCA)
- Lung cancer: Open Targets association 0.80 with lung cancer (MONDO_0008903)
- Neuroendocrine tumours: Open Targets association 0.79 with neuroendocrine neoplasm (MONDO_0019496)
- Sarcomas: Open Targets association 0.78 with sarcoma (MONDO_0005089); IntOGen driver in 4 cohorts (LIPO, LMS, SOFT_TISSUE)
- Hepatocellular carcinoma: Open Targets association 0.63 with hepatocellular carcinoma (MONDO_0007256); IntOGen driver in 7 cohorts (HCC)
- Breast cancer: Open Targets association 0.65 with breast cancer (MONDO_0007254); CIViC evidence names this disease
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: CIViC lists 16 therapies; IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 61 cohorts; CIViC holds 18 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: Urinary Bladder Cancer; Low-Grade Glioma, NOS.
Latest papers
topQuery for this target: (TITLE:"RB1" OR ABSTRACT:"RB1" OR TITLE:"RB transcriptional corepressor 1" OR ABSTRACT:"RB transcriptional corepressor 1" OR TITLE:"Retinoblastoma-associated protein" OR ABSTRACT:"Retinoblastoma-associated protein" OR TITLE:"PPP1R130" OR ABSTRACT:"PPP1R130") 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 RB1, not a curated reading list.
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