[CCND3]
CCND3 (Cyclin D3) is a gene that encodes a protein involved in the regulation of the cell cycle. Mutations in CCND3 are implicated in various types of B-cell lymphomas, including Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL).
Mutation tier
| Entity | Tier | Description |
|---|---|---|
| BL | 1 | high-confidence BL gene |
| DLBCL | 1 | high-confidence DLBCL gene |
| FL | 1 | high-confidence FL gene |
Mutation incidence
| Entity | source | frequency (%) |
|---|---|---|
| BL | GAMBL genomes+capture | 27.48 |
| BL | Thomas cohort | 28.00 |
| BL | Panea cohort | 17.80 |
| DLBCL | GAMBL genomes | 7.46 |
| DLBCL | Schmitz cohort | 9.80 |
| DLBCL | Reddy cohort | 3.80 |
| DLBCL | Chapuy cohort | 4.70 |
| FL | GAMBL genomes | 3.23 |
Mutation pattern
| Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
|---|---|---|---|---|
| BL | No | Yes | 97.799 | 360.774 |
| DLBCL | No | Yes | 19.557 | 60.833 |
| FL | No | No | 24.611 | 0.000 |
[!NOTE] First described in BL in 2012 by Schmitz R. First described in DLBCL in 2011 by Morin RD. First described in FL in 2011 by Morin RD
CCND3 Hotspots
Exon 5 Hotspot
E283 (Glutamic Acid 283): One of the most frequently mutated sites in CCND3. Mutations at this site can result in enhanced cyclin D3 stability and increased cell cycle progression.
D290 (Aspartic Acid 290): Another common mutation in exon 5. Mutations here are associated with similar functional impacts as E283, promoting uncontrolled cell proliferation.
Exon 1 and Exon 2
While exon 5 is the primary hotspot, mutations in exon 1 and exon 2 have also been observed, though less frequently. These mutations can affect the regulatory regions of the gene, potentially increasing levels of CCND3 by promoting stability of the protein.
Functional Impact of CCND3 Mutations
Cell Cycle Dysregulation: CCND3, along with other cyclins, regulates the transition from the G1 phase to the S phase of the cell cycle. Mutations in CCND3 can lead to its overexpression or increased stability, resulting in accelerated cell cycle progression and uncontrolled cell division.
Increased Protein Stability: Mutations at E283 and D290 often result in the increased stability of the cyclin D3 protein, preventing its degradation. This leads to sustained activation of CDK4/6 (cyclin-dependent kinases), further driving cell cycle progression.
Oncogenic Potential: The dysregulation of CCND3 due to these mutations contributes to the oncogenic potential of B-cell lymphomas. By promoting continuous cell proliferation, these mutations help lymphoma cells evade normal growth control mechanisms.
| Chromosome | Coordinate (hg19) | ref>alt | HGVSp |
|---|---|---|---|
| chr6 | 41903736 | C>G | S274T |
| chr6 | 41903731 | G>A | Q276* |
| chr6 | 41903719 | G>A | Q280* |
| chr6 | 41903710 | T>G | T283P |
| chr6 | 41903710 | T>C | T283A |
| chr6 | 41903710 | T>A | T283S |
| chr6 | 41903709 | G>A | T283I |
| chr6 | 41903707 | G>A | P284S |
| chr6 | 41903706 | G>C | P284R |
| chr6 | 41903706 | G>A | P284L |
| chr6 | 41903694 | G>C | T288R |
| chr6 | 41903692 | C>G | A289P |
| chr6 | 41903691 | G>C | A289G |
| chr6 | 41903688 | A>T | I290K |
| chr6 | 41903688 | A>G | I290T |
| chr6 | 41903688 | A>C | I290R |
| chr6 | 41903682 | A>T | L292Q |
| chr6 | 41903682 | A>C | L292R |
View coding variants in ProteinPaint hg19 or hg38
View all variants in GenomePaint hg19 or hg38
References
Schmitz, R., et al. (2012). “Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics.” Nature, 490(7418), 116-120.
Citing
If you use the information or data from this site, please cite
Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.
Disclaimer
The content in these pages has been populated, in part, by an automated process. Although we have scrutinized every page to ensure accuracy, errors will inevitably exist. If you find an error please report it as an issue and we will address it.
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
Share — copy and redistribute the material in any medium or format for any purpose, even commercially.
Adapt — remix, transform, and build upon the material for any purpose, even commercially. The licensor cannot revoke these freedoms as long as you follow the license terms.
