{"entity":{"id":"ccnd3","kind":"target","name":"CCND3","aka":["cyclin D3","G1/S-specific cyclin-D3"],"tldr":"CCND3 (G1/S-specific cyclin-D3) 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 Non-Hodgkin lymphoma, Leukaemia, Breast cancer and 4 more.","summary":"Regulatory component of the cyclin D3-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 5 clinical evidence items and 0 assertions across 3 variants, naming Palbociclib. Open Targets scores its association with cancer at 0.65 (direct and indirect evidence; datatypes affected pathway 0.61, literature 0.93, genetic association 0.00, somatic mutation 0.97, animal model 0.47). IntOGen calls it a driver in 5 cohorts (3 activating, 2 loss-of-function), covering Burkitt Lymphoma, Diffuse Large B-Cell Lymphoma, NOS, Malignant Lymphoma, Non-Hodgkin Lymphoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:1585","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1585"},{"label":"UniProt P30281","url":"https://www.uniprot.org/uniprotkb/P30281/entry"},{"label":"NCBI Gene 896","url":"https://www.ncbi.nlm.nih.gov/gene/896"},{"label":"Ensembl ENSG00000112576","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000112576"},{"label":"Schmitz et al., Nature 2012: Burkitt lymphoma pathogenesis from structural and functional genomics","url":"https://doi.org/10.1038/nature11378"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["non-hodgkin-lymphoma","leukaemia","breast-cancer","dlbcl","nsclc","burkitt-lymphoma","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["bcr-signalling","pi3k-akt-mtor","cell-cycle-engine-cdks"],"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: CIViC lists 1 therapies; IntOGen calls it an activating (Act) driver in 3 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 5 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: T-cell Lymphoblastic Leukaemia/lymphoma.","Lymphoma, TCF3, ID3 and CCND3 in Burkitt lymphoma: A MYC translocation alone does not make a Burkitt lymphoma; it needs a partner that supplies survival. In Burkitt the partner is tonic B-cell receptor signalling through TCF3, the transcription factor also known as E2A: mutations either activate TCF3 or inactivate its negative regulator ID3, and TCF3 then switches on the PI3K pathway partly by augmenting tonic receptor signalling. A second, independent lesion drives the cell cycle directly, through CCND3 mutations that produce unusually stable cyclin D3. Frequency: TCF3 or ID3 mutation in 70% of sporadic Burkitt lymphoma cases and oncogenic CCND3 mutations in 38%, in a study combining high-throughput RNA sequencing with RNA interference screening (Schmitz 2012). What it changes about treatment: Not yet, and the gap is uncomfortable, because the regimens that cure Burkitt lymphoma are the most toxic in lymphoma and are the reason the disease is hard to treat in older patients and in low-resource settings, which is exactly where the endemic form occurs."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"CCND3","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:1585","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1585","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P30281","url":"https://www.uniprot.org/uniprotkb/P30281/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CCND3","url":"https://civicdb.org/features/10","note":"5 evidence items, 0 assertions, 3 variants; diseases: T-cell Lymphoblastic Leukaemia/lymphoma, Diffuse Large B-cell Lymphoma, Lung Squamous Cell Carcinoma, Burkitt Lymphoma, Cancer (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000112576","url":"https://platform.opentargets.org/target/ENSG00000112576/associations","note":"association with cancer (MONDO_0004992) 0.65; per-cancer scores at or above 0.5: acute lymphoblastic leukaemia 0.51, diffuse large B-cell lymphoma 0.55, non-Hodgkin lymphoma 0.69, breast cancer 0.53, leukaemia 0.54 (GraphQL API, CC0)"},{"label":"IntOGen CCND3","url":"https://www.intogen.org/search?gene=CCND3","note":"driver in 5 cohorts (Act 3, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"few-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 CCND3: RNA tissue enhanced (lymphoid tissue 239 nTPM); high antibody staining in 6 normal tissues; highest cancer staining carcinoid (2 of 4 high). Distribution: 4 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Leukaemia, Breast cancer (all types), Lung cancer (all types)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P30281","url":"https://www.uniprot.org/uniprotkb/P30281/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CCND3","url":"https://civicdb.org/features/10","note":"5 evidence items, 0 assertions, 3 variants; diseases: T-cell Lymphoblastic Leukaemia/lymphoma, Diffuse Large B-cell Lymphoma, Lung Squamous Cell Carcinoma, Burkitt Lymphoma, Cancer (GraphQL API, CC0)"},{"label":"IntOGen CCND3","url":"https://www.intogen.org/search?gene=CCND3","note":"driver in 5 cohorts (Act 3, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas CCND3 tissue","url":"https://www.proteinatlas.org/ENSG00000112576-CCND3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000112576 associations","url":"https://platform.opentargets.org/target/ENSG00000112576/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:1585","ensembl":"ENSG00000112576","uniprot":"P30281","entrez":"896","firstDescribed":1992,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Xiong et al, Genomics, 1992, \"Molecular cloning and chromosomal mapping of CCND genes encoding human D-type cyclins\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1386336/","biology":"Regulatory component of the cyclin D3-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. Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Shows transcriptional coactivator activity with ATF5 independently of CDK4. Location: Nucleus; Cytoplasm (UniProt). Locus 6p21.1 (HGNC).","whereFound":["Non-Hodgkin lymphoma: Open Targets association 0.69 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM, NHL)","Leukaemia: Open Targets association 0.54 with leukaemia (MONDO_0005059)","Breast cancer: Open Targets association 0.53 with breast cancer (MONDO_0007254)","Diffuse large B-cell lymphoma: Open Targets association 0.55 with diffuse large B-cell lymphoma (MONDO_0018905); CIViC evidence names this disease","Non-small-cell lung cancer: CIViC evidence names this disease","Burkitt lymphoma: CIViC evidence names this disease; IntOGen driver in 2 cohorts (BL)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/ccnd3/","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":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"burkitt-lymphoma","kind":"cancer","name":"Burkitt lymphoma","route":"/cancers/burkitt-lymphoma/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"pathway":[{"id":"bcr-signalling","kind":"pathway","name":"B-cell receptor / BTK signalling (to NF-κB)","route":"/pathways/bcr-signalling/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"cell-cycle-engine-cdks","kind":"pathway","name":"The cell-cycle engine (cyclins & CDKs)","route":"/pathways/cell-cycle-engine-cdks/"}]}}