# CCND3

Source: https://onco.cc/targets/ccnd3/  
OnCo record `ccnd3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: cyclin D3; G1/S-specific cyclin-D3
- Tags: cancer-genes-wave
- Symbol: CCND3
- Class: transcription
- 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).
- Where found: 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

- 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.

## Sources

- HGNC HGNC:1585: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1585
- UniProt P30281: https://www.uniprot.org/uniprotkb/P30281/entry
- NCBI Gene 896: https://www.ncbi.nlm.nih.gov/gene/896
- Ensembl ENSG00000112576: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000112576
- Schmitz et al., Nature 2012: Burkitt lymphoma pathogenesis from structural and functional genomics: https://doi.org/10.1038/nature11378

## 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: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Burkitt lymphoma](https://onco.cc/cancers/burkitt-lymphoma/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- pathways: [B-cell receptor / BTK signalling (to NF-κB)](https://onco.cc/pathways/bcr-signalling/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [The cell-cycle engine (cyclins & CDKs)](https://onco.cc/pathways/cell-cycle-engine-cdks/)

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JSON: https://onco.cc/api/v1/entities/ccnd3.json