CCND3
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.
Overview
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.
CIViC 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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at CCND3 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Sources: HGNC HGNC:1585 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P30281 (protein name, function text, keywords and locations (REST API)); CIViC gene CCND3 (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)); Open Targets ENSG00000112576 (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)); IntOGen CCND3 (driver in 5 cohorts (Act 3, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- 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)
Notes
top- 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.
Latest papers
topQuery for this target: (TITLE:"CCND3" OR ABSTRACT:"CCND3" OR TITLE:"cyclin D3" OR ABSTRACT:"cyclin D3" OR TITLE:"G1/S-specific cyclin-D3" OR ABSTRACT:"G1/S-specific cyclin-D3") 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 CCND3, not a curated reading list.
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