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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.
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.
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.
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.
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.
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.
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 RB1: RNA low tissue specificity; high antibody staining in 12 normal tissues; highest cancer staining breast cancer (2 of 10 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Bladder & urothelial cancer, Lung cancer (all types), Neuroendocrine tumours, Sarcomas (soft tissue, bone, GIST), Hepatocellular carcinoma, Breast cancer (all types), Skin cancer (all types) and more); Open Targets associates it with 16 specific cancer types at or above 0.5 (retinoblastoma, hereditary retinoblastoma, urinary bladder cancer, urinary bladder carcinoma, small cell lung carcinoma, non-hereditary retinoblastoma and more). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt P06400; CIViC gene RB1; IntOGen RB1; Human Protein Atlas RB1 tissue; Open Targets ENSG00000139687 associations
First described 1987. Earliest sequence paper UniProt cites for the protein: Lee W.-H. et al, Nature, 1987, "The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity". Source.
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)
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Appendix, Bone marrow, Bronchus, Cerebral cortex, Colon, Duodenum, Endometrium, Epididymis.
Medium only: carcinoid, endometrial cancer, glioma, head and neck 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.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Small-cell lung cancer | 73-100% | Biallelic inactivation | cBioPortal: 87 of 120, 72.5%, carry a non-synonymous RB1 mutation in sclc_ucologne_2015, against 34 of 566, 6.0%, in lung adenocarcinoma. Biallelic inactivation was found in nearly all of the 110 sequenced genomes, and the two tumours with wild-type RB1 showed chromothripsis leading to cyclin D1 overexpression, an alternative route to the same deregulation (George 2015). | cBioPortal (TCGA) |
| Triple-negative breast cancer | 15-20% | Mutation or deletion (loss) | RB1 mutation or loss in 20% of basal-like tumours (Cancer Genome Atlas 2012); RB1 loss of heterozygosity in 72% of basal-like tumours among 88 carcinomas, with low RB1 mRNA (Herschkowitz 2008); cBioPortal: deep deletion in 13 of 119, 10.9%, and mutation in 6 of 123, 4.9%, in brca_tcga_pan_can_atlas_2018; mutation in 18 of 299, 6.0%, and deep deletion in 8 of 320, 2.5%, in brca_metabric; mutation in 17 of 176, 9.7%, and deep deletion in 11 of 176, 6.2%, in breast_msk_2018. Copy-number deletion of RB1 marked the BL1 subtype (Bareche 2018). | doi.org |
| Prostate cancer | 3-23% | Deep deletion, and inactivating mutation | cBioPortal deep deletion: 46 of 489, 9.4%, in prad_tcga_pan_can_atlas_2018; 41 of 1,013, 4.0%, in prad_p1000; 13 of 424, 3.1%, in prad_mcspc_mskcc_2020; 76 of 2,260, 3.4%, in prostate_msk_2024; 43 of 444, 9.7%, in prad_su2c_2019; 29 of 149, 19.5%, in prad_fhcrc; 14 of 61, 23.0%, in prad_mich. Mutation adds 1.5 to 10% (16 of 444, 3.6%, in prad_su2c_2019; 8 of 114, 7.0%, in nepc_wcm_2016). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It splits the alterations into two groups with different practical meanings. The repair defects are present at diagnosis at close to their castration-resistant prevalence, so testing early is worthwhile; AR, TP53 and RB1 changes accumulate later, so a diagnostic sample does not answer questions about the disease in front of you at relapse.
It gives the sequencing report a prognostic reading that does not depend on a repeat biopsy: an EGFR-mutant cancer that also carries RB1 and TP53 alterations will stop responding sooner and should be watched for a change of histology.
It is the practical guide to what to do after transformation: treat it as small-cell lung cancer with platinum and etoposide, expect central nervous system disease, and do not expect a checkpoint inhibitor to help.
Re-biopsy and re-sequencing at relapse can find repair defects and a higher mutation burden that the primary did not show, which matters for PARP inhibitor and immunotherapy eligibility in metastatic TNBC.
It is the most disciplined outcome analysis in this disease and its result is deflationary in a useful way: most of the alterations people quote as prognostic do not survive adjustment, and the one that does, RB1, is also the one that marks the route to neuroendocrine transformation.
What a prostate cancer sequencing report looks like in practice, and the numerical basis for two clinical rules: do not expect checkpoint immunotherapy to work unless the tumour is mismatch repair deficient, and do not treat a CDK12 alteration as if it were a BRCA alteration.
This is the sourced bridge between expression subtype and mutation: it tells a clinician that a LAR tumour is the one to sequence for PIK3CA and AKT1, and that immunomodulatory biology is a favourable prognostic group before any immunotherapy.
It made transformation predictable from the first biopsy, using two stains that most pathology laboratories can already run, which is the practical way to know which patients need close watching and early rebiopsy.
Query 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.
Shares Comprehensive molecular portraits of human breast tumours, Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis, Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers, Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer.
Shares Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis and antiandrogen resistance, Comprehensive genomic characterization of squamous cell lung cancers, SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer, Lineage plasticity & neuroendocrine transformation.
Shares Comprehensive genomic characterization of squamous cell lung cancers, Hepatocellular carcinoma (KEGG map), Oesophageal cancer, Bladder & urothelial cancer.
Shares Bladder cancer (KEGG map), Neuroendocrine tumours, Sarcomas (soft tissue, bone, GIST), Bladder & urothelial cancer.
Shares Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers, Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer, Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis and antiandrogen resistance, Neuroendocrine differentiation in prostate cancer.
Shares Genomics of lethal prostate cancer at diagnosis and castration resistance, Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours, Skin cancer (all types), Bladder & urothelial cancer.
Shares Hepatocellular carcinoma (KEGG map), Skin cancer (all types), Bladder & urothelial cancer, CIViC.
Shares Genomic characterization of metastatic breast cancers, Genomic correlates of clinical outcome in advanced prostate cancer, Comprehensive molecular portraits of human breast tumours, Clonal history and genetic predictors of transformation into small-cell carcinomas from lung adenocarcinomas.