CCND2: Cyclin D2 – Cell Cycle Regulator and Oncogene
Comprehensive genomic and clinical overview of CCND2, a key G1/S cell cycle checkpoint protein implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | CCND2 |
|---|---|
| Full Name | Cyclin D2 |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.32 |
| NCBI Gene ID | 894 ncbi.nlm.nih.gov/gene/894 |
| Ensembl ID | ENSG00000118971 |
| UniProt ID | P30279 |
| OMIM ID | 123833 |
| HGNC ID | 1583 |
| Aliases | CCND2, cyclin D2, KIAK0002 |
Description
CCND2 encodes cyclin D2, a member of the D-type cyclin family that regulates G1/S phase transition of the cell cycle. Cyclin D2 forms a complex with CDK4 or CDK6, phosphorylating the retinoblastoma protein (RB1) to promote cell cycle progression. Overexpression or gain-of-function mutations in CCND2 are oncogenic, while loss-of-function variants are linked to developmental brain disorders such as megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) | Gain-of-function mutations increase CDK4/6 activity, driving aberrant cell proliferation in neural progenitors | PMID: 24726877, ClinVar |
| Glioblastoma | Amplification and overexpression of CCND2 promote tumor growth and resistance to therapy | PMID: 25485619, COSMIC |
| Breast cancer | CCND2 overexpression correlates with poor prognosis and endocrine therapy resistance | PMID: 23454898, NCBI Gene |
| Colorectal cancer | CCND2 upregulation via Wnt/β-catenin signaling enhances proliferation | PMID: 21804531, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 2.4 | Not detected |
| Kidney | 5.0 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.5 | High expression |
| HeLa | 22.3 | High expression |
| MCF7 | 14.0 | Medium expression |
| U87MG (glioblastoma) | 25.1 | Very high expression |
| HCT116 | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.832G>A (p.Glu278Lys) | Missense | Rare | Gain-of-function; increases CDK4/6 binding affinity |
| c.914A>G (p.Tyr305Cys) | Missense | Rare | Gain-of-function; associated with MPPH syndrome |
| Amplification | Copy number gain | Common in glioblastoma | Overexpression drives proliferation |
| c.1-?_*?del | Deletion | Very rare | Loss-of-function; potential tumor suppressor effect |
Mutation functional classification
Loss of Function (LOF)
Rare deletions or truncating mutations reduce cyclin D2 activity, impairing cell cycle progression; may act as tumor suppressor in some contexts.
Gain of Function (GOF)
Missense mutations (e.g., Glu278Lys, Tyr305Cys) enhance CDK4/6 binding and kinase activity, promoting uncontrolled proliferation and oncogenesis.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for CCND2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cell Cycle (KEGG hsa04110)
• p53 signaling pathway (KEGG hsa04115)
• PI3K-Akt signaling pathway (KEGG hsa04151)
• CDK4/6-RB1 pathway (Reactome R-HSA-69278)
Protein Summary
Cyclin D2 is a 289-amino acid protein (32.7 kDa) containing a cyclin N-terminal domain and a cyclin C-terminal domain. It localizes to the nucleus and cytoplasm, binding CDK4/6 to phosphorylate RB1 and release E2F transcription factors, enabling S-phase entry. Post-translational modifications include phosphorylation at Thr280 (stabilization) and ubiquitination (degradation).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CCND2 Knockout HEK293 Cell Line | EDJ-KQ884 | Human | 894 | Details Get a Quote |
| CCND2 Knockout HeLa Cell Line | EDJ-KQ52805 | Human | 894 | Details Get a Quote |
| CCND2 Knockout A-549 Cell Line | EDJ-KQ61276 | Human | 894 | Details Get a Quote |
| CCND2 Knockout HCT 116 Cell Line | EDJ-KQ69771 | Human | 894 | Details Get a Quote |
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