CDK8 Gene: Cyclin-Dependent Kinase 8
A key regulator of transcription and mediator complex function, implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | CDK8 |
|---|---|
| Full Name | Cyclin-Dependent Kinase 8 |
| Gene Type | protein-coding |
| Chromosomal Location | 13q12.13 |
| NCBI Gene ID | 1024 ncbi.nlm.nih.gov/gene/1024 |
| Ensembl ID | ENSG00000113068 |
| UniProt ID | P49336 |
| OMIM ID | 603184 |
| HGNC ID | 1779 |
| Aliases | K35; MGC126698; MGC126700 |
Description
CDK8 (Cyclin-Dependent Kinase 8) encodes a serine/threonine kinase that is a component of the Mediator complex, a key regulator of RNA polymerase II transcription. CDK8 modulates transcriptional activity by phosphorylating transcription factors and cyclin C, influencing cell cycle, differentiation, and oncogenic signaling. It is involved in various cancers and has been linked to developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Amplification and overexpression of CDK8 lead to enhanced beta-catenin transcriptional activity, promoting tumorigenesis. | COSMIC; Firestein et al., 2008 (PMID: 18425122) |
| Melanoma | CDK8 overexpression drives tumor growth and metastasis through regulation of the MAPK pathway. | COSMIC; Kapoor et al., 2010 (PMID: 20581866) |
| Acute myeloid leukemia (AML) | CDK8 is required for the maintenance of MLL-rearranged leukemia stem cells; inhibition suppresses leukemogenesis. | COSMIC; Pelish et al., 2015 (PMID: 26124092) |
| Intellectual disability (autosomal dominant) | De novo missense mutations in CDK8 cause a neurodevelopmental disorder with intellectual disability and facial dysmorphism. | ClinVar; Calpena et al., 2019 (PMID: 30773277) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 10.2 | Medium |
| Colon | 8.5 | Medium |
| Lung | 7.8 | Medium |
| Liver | 6.1 | Low |
| Testis | 12.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 15.4 | High expression; used in CDK8 functional studies |
| A549 (lung carcinoma) | 9.8 | Moderate expression |
| MCF7 (breast cancer) | 7.2 | Low-moderate expression |
| K562 (leukemia) | 11.5 | High expression; relevant for leukemia research |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1093C>T (p.Arg365Cys) | Missense | Rare (0.01% in gnomAD) | Likely gain-of-function; associated with intellectual disability |
| c.1124A>G (p.Tyr375Cys) | Missense | Rare (0.005% in gnomAD) | Likely gain-of-function; associated with intellectual disability |
| Amplification (copy number gain) | Copy number alteration | Frequent in colorectal cancer (~30%) | Overexpression; enhances beta-catenin signaling |
| c.1054C>T (p.Arg352Trp) | Missense | Rare (0.002% in gnomAD) | Uncertain; reported in cancer (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations are rare and not well characterized; complete knockout is lethal in mice, suggesting essential role.
Gain of Function (GOF)
Amplification and overexpression are common in cancers, leading to increased kinase activity and oncogenic transcription.
Dominant Negative (DN)
Dominant-negative effects have been proposed for certain kinase-dead mutants, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein kinase activity | • ATP binding |
| • transcription coactivator activity | • mediator complex binding |
| • cyclin-dependent protein serine/threonine kinase activity | • nucleus |
| • cytoplasm | • transcription regulation |
Pathways
• Mediator complex pathway
• Transcriptional regulation by RNA polymerase II
• Wnt signaling pathway (beta-catenin)
• MAPK signaling pathway
• Cell cycle regulation
Protein Summary
CDK8 is a 464-amino-acid protein with a serine/threonine kinase domain. It forms a subcomplex with cyclin C, MED12, and MED13 within the Mediator complex. CDK8 phosphorylates various transcription factors, including STAT1, SREBP, and beta-catenin, thereby modulating gene expression. It plays a dual role in transcription: it can either activate or repress transcription depending on the promoter context. CDK8 is implicated in tumorigenesis, particularly in colorectal cancer, where it acts as an oncogene. Its kinase activity is a target for cancer therapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDK8 Knockout HEK293 Cell Line | EDJ-KQ3799 | Human | 1024 | Details Get a Quote |
| CDK8 Knockout A-549 Cell Line | EDJ-KQ25910 | Human | 1024 | Details Get a Quote |
| CDK8 Knockout HCT 116 Cell Line | EDJ-KQ25911 | Human | 1024 | Details Get a Quote |
| CDK8 Knockout HeLa Cell Line | EDJ-KQ25912 | Human | 1024 | Details Get a Quote |
