{"entity":{"id":"ccnd1","kind":"target","name":"CCND1","aka":["cyclin D1","G1/S-specific cyclin-D1","U21B31","BCL1","D11S287E","PRAD1"],"tldr":"CCND1 (G1/S-specific cyclin-D1) 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, a biomarker, a fusion partner and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Breast cancer, Skin cancer, Multiple myeloma and 5 more.","summary":"Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase.\n\nCIViC holds 23 clinical evidence items and 0 assertions across 5 variants, naming Palbociclib, Tamoxifen, Ribociclib and Sorafenib and others. Open Targets scores its association with cancer at 0.86 (direct and indirect evidence; datatypes clinical 0.97, genetic literature 0.61, affected pathway 0.80, literature 1.00, genetic association 0.70, somatic mutation 0.93, animal model 0.56). IntOGen calls it a driver in 4 cohorts (2 activating, 2 loss-of-function), covering Head and Neck Squamous Cell Carcinoma, Plasma Cell Myeloma, Endometrial Carcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:1582","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1582"},{"label":"UniProt P24385","url":"https://www.uniprot.org/uniprotkb/P24385/entry"},{"label":"NCBI Gene 595","url":"https://www.ncbi.nlm.nih.gov/gene/595"},{"label":"Ensembl ENSG00000110092","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110092"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["breast-cancer","skin-cancer","multiple-myeloma","ovarian","head-and-neck","rcc","colorectal","endometrial"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"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: Open Targets known-drug datatype score 0.97; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 23 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene; UniProt keyword \"DNA damage\". Evidence tier \"approved-drug\" 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: Childhood B-cell Acute Lymphoblastic Leukaemia; Anaplastic Thyroid Carcinoma."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"CCND1","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker","fusion-partner","dna-repair"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:1582","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1582","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P24385","url":"https://www.uniprot.org/uniprotkb/P24385/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CCND1","url":"https://civicdb.org/features/8","note":"23 evidence items, 0 assertions, 5 variants; diseases: Breast Cancer, Lung Non-small Cell Carcinoma, Mantle Cell Lymphoma, Cancer, Ovarian Cancer and 8 more (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000110092","url":"https://platform.opentargets.org/target/ENSG00000110092/associations","note":"association with cancer (MONDO_0004992) 0.86; per-cancer scores at or above 0.5: colorectal cancer 0.58, prostate cancer 0.54, endometrial cancer 0.51, melanoma 0.63, plasma cell myeloma 0.53, non-Hodgkin lymphoma 0.57 (GraphQL API, CC0)"},{"label":"IntOGen CCND1","url":"https://www.intogen.org/search?gene=CCND1","note":"driver in 4 cohorts (Act 2, LoF 2); 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) and a fusion partner (UniProt records a translocation), 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 CCND1: RNA low tissue specificity; high antibody staining in 15 normal tissues; highest cancer staining renal cancer (11 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Skin cancer (all types), Multiple myeloma, Ovarian cancer, Head and neck squamous cell carcinoma, Renal cell carcinoma, Colorectal cancer and more); Open Targets associates it with 4 specific cancer types at or above 0.5 (breast cancer, breast carcinoma, prostate carcinoma, plasma cell myeloma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P24385","url":"https://www.uniprot.org/uniprotkb/P24385/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CCND1","url":"https://civicdb.org/features/8","note":"23 evidence items, 0 assertions, 5 variants; diseases: Breast Cancer, Lung Non-small Cell Carcinoma, Mantle Cell Lymphoma, Cancer, Ovarian Cancer and 8 more (GraphQL API, CC0)"},{"label":"IntOGen CCND1","url":"https://www.intogen.org/search?gene=CCND1","note":"driver in 4 cohorts (Act 2, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas CCND1 tissue","url":"https://www.proteinatlas.org/ENSG00000110092-CCND1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000110092 associations","url":"https://platform.opentargets.org/target/ENSG00000110092/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:1582","ensembl":"ENSG00000110092","uniprot":"P24385","entrez":"595","firstDescribed":1991,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Motokura et al, Nature, 1991, \"A novel cyclin encoded by a bcl1-linked candidate oncogene\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1826542/","biology":"Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Location: Nucleus; Cytoplasm; Nucleus membrane (UniProt). Locus 11q13.3 (HGNC).","whereFound":["Breast cancer: Open Targets association 0.75 with breast cancer (MONDO_0007254); CIViC evidence names this disease","Skin cancer: Open Targets association 0.64 with skin cancer (MONDO_0002898)","Multiple myeloma: Open Targets association 0.53 with plasma cell myeloma (MONDO_0009693); CIViC evidence names this disease","Ovarian cancer: CIViC evidence names this disease","Head and neck squamous cell carcinoma: CIViC evidence names this disease; IntOGen driver in 1 cohort (HNSC)","Renal cell carcinoma: CIViC evidence names this disease"],"targetClass":"transcription","prevalence":[]},"route":"/targets/ccnd1/","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":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"trial":[{"id":"nct02972840","kind":"trial","name":"A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL","route":"/trials/nct02972840/"},{"id":"enrich","kind":"trial","name":"ENRICH","route":"/trials/enrich/"},{"id":"lyma","kind":"trial","name":"LyMa","route":"/trials/lyma/"},{"id":"shine","kind":"trial","name":"SHINE","route":"/trials/shine/"}],"paper":[{"id":"paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-2025","kind":"paper","name":"Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma","route":"/key-papers/paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-2025/"},{"id":"paper-enrich-ibrutinib-rituximab-mantle-cell-lancet-2025","kind":"paper","name":"Ibrutinib and rituximab versus immunochemotherapy in patients with previously untreated mantle cell lymphoma (ENRICH): a randomised, open-label, phase 2/3 superiority trial","route":"/key-papers/paper-enrich-ibrutinib-rituximab-mantle-cell-lancet-2025/"},{"id":"paper-shine-ibrutinib-bendamustine-rituximab-mantle-cell-nejm-2022","kind":"paper","name":"Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma","route":"/key-papers/paper-shine-ibrutinib-bendamustine-rituximab-mantle-cell-nejm-2022/"},{"id":"paper-lyma-rituximab-maintenance-after-transplant-mantle-cell-nejm-2017","kind":"paper","name":"Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma","route":"/key-papers/paper-lyma-rituximab-maintenance-after-transplant-mantle-cell-nejm-2017/"}],"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}],"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"},{"id":"cyclin-d1-t11-14","kind":"term","name":"t(11;14), cyclin D1 and SOX11","route":"/terms/cyclin-d1-t11-14/"}]}}