# RB1

Source: https://onco.cc/targets/rb1/  
OnCo record `rb1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: RB transcriptional corepressor 1; Retinoblastoma-associated protein; PPP1R130
- Tags: cancer-genes-wave
- Symbol: RB1
- Class: transcription
- 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).
- Where found: 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; Triple-negative breast cancer: mutation or deletion (loss) 15-20%; Small-cell lung cancer: biallelic inactivation 73-100%; Prostate cancer: deep deletion, and inactivating mutation 3-23% depending on disease state

## Notes

- 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.
- Triple-negative breast cancer: RB1 mutation or loss in 20% of basal-like tumours (Cancer Genome Atlas 2012), loss of heterozygosity in 72% (Herschkowitz 2008); the reason CDK4/6 inhibition has no role in most TNBC and the LAR subtype, which keeps RB1, is the exception being tested.
- Lung cancer: mutated in 72.5% of small-cell tumours on a mutation call and biallelically inactivated in nearly all of them once complex rearrangements are counted, with the two RB1 wild-type cases in the sequencing series reaching the same end through chromothripsis and cyclin D1 overexpression (George 2015). In adenocarcinoma it is 5 to 6%, and the cases that matter are those where it accompanies TP53 loss in an EGFR-mutant tumour: that combination carries a 43-fold risk of transformation to small-cell carcinoma (Lee 2017, Offin 2019).

## Sources

- HGNC HGNC:9884: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9884
- UniProt P06400: https://www.uniprot.org/uniprotkb/P06400/entry
- NCBI Gene 5925: https://www.ncbi.nlm.nih.gov/gene/5925
- Ensembl ENSG00000139687: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000139687

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- pathways: [Bladder cancer (KEGG map)](https://onco.cc/pathways/bladder-cancer-signalling/), [Cancer stem cells & phenotypic plasticity](https://onco.cc/pathways/cancer-stem-cells-plasticity/), [Chronic myeloid leukaemia (KEGG map)](https://onco.cc/pathways/cml-signalling/), [Hepatocellular carcinoma (KEGG map)](https://onco.cc/pathways/hepatocellular-carcinoma-signalling/), [Lineage plasticity & neuroendocrine transformation](https://onco.cc/pathways/lineage-plasticity-neuroendocrine/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [Resistance routes: how a blocked pathway comes back](https://onco.cc/pathways/resistance-routes-map/), [Small cell lung cancer (KEGG map)](https://onco.cc/pathways/sclc-signalling/)
- terms: [Checkpoint (two meanings)](https://onco.cc/terms/checkpoint/), [Histologic transformation](https://onco.cc/terms/histologic-transformation/), [Neuroendocrine differentiation in prostate cancer](https://onco.cc/terms/neuroendocrine-differentiation/)
- key papers: [Clonal history and genetic predictors of transformation into small-cell carcinomas from lung adenocarcinomas](https://onco.cc/key-papers/paper-lee-clonal-history-small-cell-transformation-jco-2017/), [Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers](https://onco.cc/key-papers/paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016/), [Comprehensive genomic characterization of squamous cell lung cancers](https://onco.cc/key-papers/paper-tcga-lung-squamous-nature-2012/), [Comprehensive genomic profiles of small cell lung cancer](https://onco.cc/key-papers/paper-george-sclc-genomic-profiles-nature-2015/), [Comprehensive molecular portraits of human breast tumours](https://onco.cc/key-papers/paper-tcga-breast-molecular-portraits-nature-2012/), [Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer](https://onco.cc/key-papers/paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017/), [Concurrent RB1 and TP53 alterations define a subset of EGFR-mutant lung cancers at risk for histologic transformation and inferior clinical outcomes](https://onco.cc/key-papers/paper-offin-rb1-tp53-transformation-risk-jto-2019/), [Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer](https://onco.cc/key-papers/paper-beltran-nepc-divergent-evolution-nat-med-2016/), [EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes](https://onco.cc/key-papers/paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019/), [Genomic characterization of metastatic breast cancers](https://onco.cc/key-papers/paper-bertucci-metastatic-breast-genomics-nature-2019/), [Genomic correlates of clinical outcome in advanced prostate cancer](https://onco.cc/key-papers/paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019/), [Genomics of lethal prostate cancer at diagnosis and castration resistance](https://onco.cc/key-papers/paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020/), [Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors](https://onco.cc/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/), [Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours](https://onco.cc/key-papers/paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019/), [Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis and antiandrogen resistance](https://onco.cc/key-papers/paper-ku-rb1-trp53-lineage-plasticity-science-2017/), [SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer](https://onco.cc/key-papers/paper-mu-sox2-lineage-plasticity-science-2017/), [Substantial interindividual and limited intraindividual genomic diversity among tumours from men with metastatic prostate cancer](https://onco.cc/key-papers/paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016/), [The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas](https://onco.cc/key-papers/paper-herschkowitz-rb1-loss-basal-like-bcr-2008/), [Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis](https://onco.cc/key-papers/paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018/)
- ideas: [Run small-cell lung cancer as one platform with shared controls and subtype stratification](https://onco.cc/ideas/idea-lung-small-cell-platform-with-shared-controls-and-subtypes/), [Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it](https://onco.cc/ideas/idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine/)
- biomarkers: [Treatment-emergent neuroendocrine transformation (recognising it)](https://onco.cc/biomarkers/nepc-transformation/)

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