CCND3: Cyclin D3 – Cell Cycle Regulator and Oncogene
Comprehensive genomic and proteomic overview of CCND3, a key G1/S cell cycle checkpoint protein implicated in hematologic malignancies and solid tumors.
Gene Information Card
| Symbol | CCND3 |
|---|---|
| Full Name | Cyclin D3 |
| Gene Type | Protein-coding |
| Chromosomal Location | 6p21.1 |
| NCBI Gene ID | 896 ncbi.nlm.nih.gov/gene/896 |
| Ensembl ID | ENSG00000112576 |
| UniProt ID | P30281 |
| OMIM ID | 123834 |
| HGNC ID | 1585 |
| Aliases | CCND3, cyclin D3, G1/S-specific cyclin-D3 |
Description
CCND3 encodes cyclin D3, a member of the D-type cyclin family that forms holoenzymes with cyclin-dependent kinases CDK4 and CDK6. This complex phosphorylates and inactivates the retinoblastoma protein (RB1), driving G1-to-S phase transition. CCND3 is frequently amplified or mutated in lymphoid malignancies, including mantle cell lymphoma, multiple myeloma, and B-cell acute lymphoblastic leukemia. Overexpression or gain-of-function mutations promote uncontrolled cell proliferation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mantle cell lymphoma | CCND3 amplification or translocation leads to cyclin D3 overexpression, driving CDK4/6-mediated RB1 phosphorylation and cell cycle progression. | COSMIC; ClinVar; PMID: 23563236 |
| Multiple myeloma | CCND3 gain-of-function mutations (e.g., p.Trp299Cys) enhance CDK4/6 binding and kinase activity, promoting proliferation. | COSMIC; ClinVar; PMID: 29247016 |
| B-cell acute lymphoblastic leukemia (B-ALL) | CCND3 rearrangements (e.g., t(6;14)(p21;q32)) result in cyclin D3 overexpression, contributing to leukemogenesis. | COSMIC; ClinVar; PMID: 23563236 |
| Breast cancer | CCND3 amplification and overexpression correlate with poor prognosis and endocrine therapy resistance. | COSMIC; PMID: 21558571 |
| Colorectal cancer | CCND3 overexpression via gene amplification or transcriptional upregulation promotes tumor growth. | COSMIC; PMID: 21558571 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Lymph node | 10.8 | Medium |
| Spleen | 9.2 | Medium |
| Thymus | 8.1 | Low |
| Testis | 7.4 | Low |
| Brain | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 15.2 | High expression |
| HeLa (cervical cancer) | 11.0 | Medium expression |
| MCF7 (breast cancer) | 9.8 | Medium expression |
| A549 (lung cancer) | 6.5 | Low expression |
| HepG2 (liver cancer) | 4.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Trp299Cys | Missense | <1% | Gain-of-function; enhances CDK4/6 binding and kinase activity |
| p.Arg298His | Missense | <1% | Gain-of-function; increases cyclin D3 stability |
| p.Leu32Pro | Missense | <1% | Loss-of-function; disrupts CDK4 binding |
| Amplification | Copy number gain | ~5% in lymphoma | Overexpression; drives cell cycle progression |
Mutation functional classification
Loss of Function (LOF)
Rare missense mutations (e.g., p.Leu32Pro) impair CDK4 binding and reduce kinase activity, potentially acting as tumor suppressors in specific contexts.
Gain of Function (GOF)
Common in lymphoid malignancies; mutations (e.g., p.Trp299Cys, p.Arg298His) enhance CDK4/6 interaction, increase cyclin D3 stability, and promote RB1 phosphorylation, driving proliferation.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for CCND3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cell Cycle (KEGG hsa04110)
• p53 signaling pathway (KEGG hsa04115)
• PI3K-Akt signaling pathway (KEGG hsa04151)
• Cyclin D-CDK4/6-RB1 pathway (Reactome R-HSA-69278)
Protein Summary
Cyclin D3 is a 292-amino-acid protein (32.7 kDa) containing a cyclin N-terminal domain (residues 1–150) that mediates CDK4/6 binding and a C-terminal domain involved in subcellular localization. It is predominantly nuclear but shuttles to the cytoplasm upon phosphorylation. Cyclin D3 is essential for normal lymphoid development and is frequently dysregulated in cancer through amplification, translocation, or activating mutations. Its interaction with CDK4/6 is a therapeutic target in hormone receptor-positive breast cancer and mantle cell lymphoma.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CCND3 Knockout HEK293 Cell Line | EDJ-KQ285 | Human | 896 | Details Get a Quote |
| CCND3 Knockout HeLa Cell Line | EDJ-KQ17962 | Human | 896 | Details Get a Quote |
| CCND3 Knockout A-549 Cell Line | EDJ-KQ18395 | Human | 896 | Details Get a Quote |
| CCND3 Knockout HCT 116 Cell Line | EDJ-KQ18396 | Human | 896 | Details Get a Quote |
| CCND3 (p.S178A) Point Mutation in HAP1 Cell Line | EDC03431 | Human | 896 | Details Get a Quote |
