CDK4 Gene: Cyclin Dependent Kinase 4
Key regulator of cell cycle G1 phase progression and oncogenic driver in melanoma and other cancers
Gene Information Card
| Symbol | CDK4 |
|---|---|
| Full Name | Cyclin Dependent Kinase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q14.1 |
| NCBI Gene ID | 1019 ncbi.nlm.nih.gov/gene/1019 |
| Ensembl ID | ENSG00000135446 |
| UniProt ID | P11802 |
| OMIM ID | 123829 |
| HGNC ID | 1773 |
| Aliases | CMM3, PSK-J3 |
Description
CDK4 (Cyclin Dependent Kinase 4) encodes a serine/threonine protein kinase that is a key regulator of the G1/S phase transition of the cell cycle. It forms a complex with cyclin D1 (CCND1) and phosphorylates the retinoblastoma protein (RB1), promoting cell cycle progression. CDK4 is frequently amplified, mutated, or overexpressed in various cancers, particularly melanoma. Gain-of-function mutations (e.g., R24C) render the protein resistant to INK4 family inhibitors, driving uncontrolled proliferation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Melanoma, cutaneous malignant, susceptibility to, 3 (CMM3) | Gain-of-function mutation (e.g., R24C) prevents binding of CDKN2A/p16INK4a, leading to constitutive CDK4 activity and uncontrolled cell cycle progression | OMIM 609048; multiple familial melanoma kindreds |
| Liposarcoma | CDK4 gene amplification (12q13-15 amplicon) leads to overexpression and increased kinase activity, promoting tumor growth | NCBI Gene; COSMIC |
| Breast cancer | CDK4 amplification and overexpression contribute to RB1 phosphorylation and cell cycle dysregulation | NCBI Gene; ClinVar |
| Glioblastoma | CDK4 amplification is a common event, driving proliferation in neural stem cells | COSMIC; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Breast | 10.2 | Medium |
| Skin | 15.8 | Medium |
| Lung | 8.4 | Low |
| Brain (cerebral cortex) | 6.1 | Low |
| Testis | 20.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A375 (melanoma) | 28.5 | High expression; consistent with melanoma cell lines |
| MCF7 (breast cancer) | 18.2 | Moderate expression |
| HeLa (cervical cancer) | 22.1 | High expression |
| HEK293 (embryonic kidney) | 14.7 | Moderate expression |
| K562 (leukemia) | 9.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R24C | Missense | ~1-2% in familial melanoma | Gain-of-function; disrupts p16INK4a binding, leading to constitutive activation |
| R24H | Missense | Rare | Gain-of-function; similar mechanism to R24C |
| Amplification | Copy number gain | ~10-15% in liposarcoma, ~5% in glioblastoma | Increased gene dosage leads to CDK4 overexpression and enhanced kinase activity |
Mutation functional classification
Loss of Function (LOF)
Rare; not commonly described. Loss-of-function mutations would impair cell cycle progression and are not typically selected in cancers.
Gain of Function (GOF)
R24C and R24H missense mutations; also gene amplification. These increase CDK4 activity by preventing inhibition by p16INK4a or by increasing protein levels.
Dominant Negative (DN)
Not reported for CDK4.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004693 - cyclin-dependent protein serine/threonine kinase activity | • GO:0005515 - protein binding |
| • GO:0005634 - nucleus | • GO:0005737 - cytoplasm |
| • GO:0007049 - cell cycle | • GO:0051726 - regulation of cell cycle |
| • GO:0000082 - G1/S transition of mitotic cell cycle | • GO:0016301 - kinase activity |
| • GO:0006468 - protein phosphorylation |
Pathways
• Cell Cycle (KEGG hsa04110)
• p53 signaling pathway (KEGG hsa04115)
• PI3K-Akt signaling pathway (KEGG hsa04151)
• Cyclin D / CDK4 pathway (Reactome R-HSA-69278)
• RB1 tumor suppressor pathway (Reactome R-HSA-69275)
Protein Summary
CDK4 is a 303-amino acid serine/threonine kinase (34 kDa) that belongs to the CMGC family of kinases. It contains a typical kinase domain with an ATP-binding site and a PSTAIRE-like cyclin-binding motif. CDK4 activity is regulated by association with D-type cyclins (CCND1, CCND2, CCND3) and inhibition by INK4 family members (p16INK4a, p15INK4b, p18INK4c, p19INK4d). The active CDK4-cyclin D complex phosphorylates RB1, releasing E2F transcription factors to drive S-phase entry. CDK4 is a validated drug target; selective inhibitors (e.g., palbociclib, ribociclib, abemaciclib) are used in breast cancer therapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDK4 Knockout HEK293 Cell Line | EDC07820 | Human | 1019 | Details Get a Quote |
| CDK4 Knockout HeLa Cell Line | EDJ-KQ52863 | Human | 1019 | Details Get a Quote |
| CDK4 Knockout A-549 Cell Line | EDJ-KQ61330 | Human | 1019 | Details Get a Quote |
| CDK4 Knockout HCT 116 Cell Line | EDJ-KQ69828 | Human | 1019 | Details Get a Quote |
| CDK4 (c.819+111G>T )Point Mutation in HAP1 Cell Line | EDC03435 | Human | 1019 | Details Get a Quote |
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