CDK8

Chr 13AD

cyclin dependent kinase 8

Also known as: IDDHBA, K35

NCBI Gene: 1024 ENSG00000132964 UniProt: P49336 OMIM: 603184

This gene encodes a cyclin-dependent kinase that is a component of the Mediator complex, which regulates transcription by serving as a bridge between gene-specific regulatory proteins and RNA polymerase II transcription machinery. Mutations cause intellectual developmental disorder with hypotonia and behavioral abnormalities with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.418), indicating that such variants are likely to be pathogenic.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are known to be important regulators of cell cycle progression. This kinase and its regulatory subunit, cyclin C, are components of the Mediator transcriptional regulatory complex, involved in both transcriptional activation and repression by phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II. This kinase regulates transcription by targeting the cyclin-dependent kinase 7 subunits of the general transcription initiation factor IIH, thus providing a link between the Mediator complex and the basal transcription machinery. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder with hypotonia and behavioral abnormalitiesMIM #618748

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

111

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.42

LOEUF

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Mechanism

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