{"entity":{"id":"rb1","kind":"target","name":"RB1","aka":["RB transcriptional corepressor 1","Retinoblastoma-associated protein","PPP1R130"],"tldr":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:9884","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9884"},{"label":"UniProt P06400","url":"https://www.uniprot.org/uniprotkb/P06400/entry"},{"label":"NCBI Gene 5925","url":"https://www.ncbi.nlm.nih.gov/gene/5925"},{"label":"Ensembl ENSG00000139687","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000139687"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["urothelial","lung-cancer","neuroendocrine","sarcoma","hcc","breast-cancer","skin-cancer","esophageal","tnbc","sclc","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["bladder-cancer-signalling","cancer-stem-cells-plasticity","cml-signalling","hepatocellular-carcinoma-signalling","lineage-plasticity-neuroendocrine","resistance-routes-map","sclc-signalling","p53-cell-cycle"],"terms":["histologic-transformation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-tcga-breast-molecular-portraits-nature-2012","paper-herschkowitz-rb1-loss-basal-like-bcr-2008","paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018","paper-george-sclc-genomic-profiles-nature-2015","paper-lee-clonal-history-small-cell-transformation-jco-2017","paper-offin-rb1-tp53-transformation-risk-jto-2019","paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019","paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016","paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020"],"journals":[],"dependsOn":[],"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)."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"RB1","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:9884","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9884","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P06400","url":"https://www.uniprot.org/uniprotkb/P06400/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene RB1","url":"https://civicdb.org/features/4795","note":"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)"},{"label":"Open Targets ENSG00000139687","url":"https://platform.opentargets.org/target/ENSG00000139687/associations","note":"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)"},{"label":"IntOGen RB1","url":"https://www.intogen.org/search?gene=RB1","note":"driver in 65 cohorts (Act 1, LoF 61); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"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.)","specificitySources":[{"label":"UniProt P06400","url":"https://www.uniprot.org/uniprotkb/P06400/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene RB1","url":"https://civicdb.org/features/4795","note":"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)"},{"label":"IntOGen RB1","url":"https://www.intogen.org/search?gene=RB1","note":"driver in 65 cohorts (Act 1, LoF 61); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas RB1 tissue","url":"https://www.proteinatlas.org/ENSG00000139687-RB1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000139687 associations","url":"https://platform.opentargets.org/target/ENSG00000139687/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:9884","ensembl":"ENSG00000139687","uniprot":"P06400","entrez":"5925","firstDescribed":1987,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/3657987/","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).","whereFound":["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"],"targetClass":"transcription","prevalence":[{"cancerId":"tnbc","pct":"15-20","measure":"Mutation or deletion (loss)","source":"https://doi.org/10.1038/nature11412","note":"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)."},{"cancerId":"sclc","pct":"73-100","measure":"Biallelic inactivation","source":"https://www.cbioportal.org/study/summary?id=sclc_ucologne_2015","note":"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)."},{"cancerId":"prostate","pct":"3-23","measure":"Deep deletion, and inactivating mutation","source":"https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018","note":"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)."}]},"route":"/targets/rb1/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"pathway":[{"id":"bladder-cancer-signalling","kind":"pathway","name":"Bladder cancer (KEGG map)","route":"/pathways/bladder-cancer-signalling/"},{"id":"cancer-stem-cells-plasticity","kind":"pathway","name":"Cancer stem cells & phenotypic plasticity","route":"/pathways/cancer-stem-cells-plasticity/"},{"id":"cml-signalling","kind":"pathway","name":"Chronic myeloid leukaemia (KEGG map)","route":"/pathways/cml-signalling/"},{"id":"hepatocellular-carcinoma-signalling","kind":"pathway","name":"Hepatocellular carcinoma (KEGG map)","route":"/pathways/hepatocellular-carcinoma-signalling/"},{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"},{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"},{"id":"sclc-signalling","kind":"pathway","name":"Small cell lung cancer (KEGG map)","route":"/pathways/sclc-signalling/"}],"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"},{"id":"histologic-transformation","kind":"term","name":"Histologic transformation","route":"/terms/histologic-transformation/"},{"id":"neuroendocrine-differentiation","kind":"term","name":"Neuroendocrine differentiation in prostate cancer","route":"/terms/neuroendocrine-differentiation/"}],"paper":[{"id":"paper-lee-clonal-history-small-cell-transformation-jco-2017","kind":"paper","name":"Clonal history and genetic predictors of transformation into small-cell carcinomas from lung adenocarcinomas","route":"/key-papers/paper-lee-clonal-history-small-cell-transformation-jco-2017/"},{"id":"paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016","kind":"paper","name":"Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers","route":"/key-papers/paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016/"},{"id":"paper-tcga-lung-squamous-nature-2012","kind":"paper","name":"Comprehensive genomic characterization of squamous cell lung cancers","route":"/key-papers/paper-tcga-lung-squamous-nature-2012/"},{"id":"paper-george-sclc-genomic-profiles-nature-2015","kind":"paper","name":"Comprehensive genomic profiles of small cell lung cancer","route":"/key-papers/paper-george-sclc-genomic-profiles-nature-2015/"},{"id":"paper-tcga-breast-molecular-portraits-nature-2012","kind":"paper","name":"Comprehensive molecular portraits of human breast tumours","route":"/key-papers/paper-tcga-breast-molecular-portraits-nature-2012/"},{"id":"paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017","kind":"paper","name":"Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer","route":"/key-papers/paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017/"},{"id":"paper-offin-rb1-tp53-transformation-risk-jto-2019","kind":"paper","name":"Concurrent RB1 and TP53 alterations define a subset of EGFR-mutant lung cancers at risk for histologic transformation and inferior clinical outcomes","route":"/key-papers/paper-offin-rb1-tp53-transformation-risk-jto-2019/"},{"id":"paper-beltran-nepc-divergent-evolution-nat-med-2016","kind":"paper","name":"Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer","route":"/key-papers/paper-beltran-nepc-divergent-evolution-nat-med-2016/"},{"id":"paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019","kind":"paper","name":"EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes","route":"/key-papers/paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019/"},{"id":"paper-bertucci-metastatic-breast-genomics-nature-2019","kind":"paper","name":"Genomic characterization of metastatic breast cancers","route":"/key-papers/paper-bertucci-metastatic-breast-genomics-nature-2019/"},{"id":"paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019","kind":"paper","name":"Genomic correlates of clinical outcome in advanced prostate cancer","route":"/key-papers/paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019/"},{"id":"paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020","kind":"paper","name":"Genomics of lethal prostate cancer at diagnosis and castration resistance","route":"/key-papers/paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020/"},{"id":"paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011","kind":"paper","name":"Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors","route":"/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/"},{"id":"paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","kind":"paper","name":"Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours","route":"/key-papers/paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019/"},{"id":"paper-ku-rb1-trp53-lineage-plasticity-science-2017","kind":"paper","name":"Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis and antiandrogen resistance","route":"/key-papers/paper-ku-rb1-trp53-lineage-plasticity-science-2017/"},{"id":"paper-mu-sox2-lineage-plasticity-science-2017","kind":"paper","name":"SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer","route":"/key-papers/paper-mu-sox2-lineage-plasticity-science-2017/"},{"id":"paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016","kind":"paper","name":"Substantial interindividual and limited intraindividual genomic diversity among tumours from men with metastatic prostate cancer","route":"/key-papers/paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016/"},{"id":"paper-herschkowitz-rb1-loss-basal-like-bcr-2008","kind":"paper","name":"The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas","route":"/key-papers/paper-herschkowitz-rb1-loss-basal-like-bcr-2008/"},{"id":"paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018","kind":"paper","name":"Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis","route":"/key-papers/paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018/"}],"idea":[{"id":"idea-lung-small-cell-platform-with-shared-controls-and-subtypes","kind":"idea","name":"Run small-cell lung cancer as one platform with shared controls and subtype stratification","route":"/ideas/idea-lung-small-cell-platform-with-shared-controls-and-subtypes/"},{"id":"idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine","kind":"idea","name":"Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it","route":"/ideas/idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine/"}],"biomarker":[{"id":"nepc-transformation","kind":"biomarker","name":"Treatment-emergent neuroendocrine transformation (recognising it)","route":"/biomarkers/nepc-transformation/"}]}}