CDK8

Chr 13q12.13

cyclin dependent kinase 8

Aliases:: K35
MANE:: ENST00000381527.8

OMIM: 603184 ↗NCBI: 1024 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

CDK8 · P49336

v62025-08-01

Predicted Aligned Error matrix for CDK8 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

79.8/ 100

Confident

464 residues

Confidence breakdown

Very high(≥ 90)61%
Confident(70–90)11%
Low(50–70)6%
Very low(< 50)22%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

intellectual developmental disorder with hypotonia and behavioral abnormalities
0.78
syndromic intellectual disability
0.46
cancer
0.40
complex neurodevelopmental disorder
0.37
autoimmune disorder of central nervous system
0.37
neurodegenerative disease
0.36
Ventriculomegaly
0.34
Abnormal facial shape
0.34
Abnormal heart morphology
0.34
Ebstein anomaly
0.34

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Cyclin-dependent kinase 8

Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression (PubMed:10993082). Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation (PubMed:15546612). Selectively regulates the interferon response by phosphorylating the transcription factor STAT1 transactivation domain (By similarity)