GAK

Chr 4

cyclin G associated kinase

Also known as: DNAJ26, DNAJC26

NCBI Gene: 2580 ENSG00000178950 UniProt: O14976

GAK encodes a protein that associates with cyclin G and CDK5 and functions as an auxilin homolog involved in clathrin-coated vesicle uncoating and clathrin-mediated endocytosis. Mutations cause autosomal recessive early-onset parkinsonism with pyramidal signs and intellectual disability. The gene is highly constrained against loss-of-function variants (LOEUF 0.408), consistent with its role in fundamental cellular trafficking processes.

GeneReviews ResearchSummary from RefSeq, UniProt

In all eukaryotes, the cell cycle is governed by cyclin-dependent protein kinases (CDKs), whose activities are regulated by cyclins and CDK inhibitors in a diverse array of mechanisms that involve the control of phosphorylation and dephosphorylation of Ser, Thr or Tyr residues. Cyclins are molecules that possess a consensus domain called the 'cyclin box.' In mammalian cells, 9 cyclin species have been identified, and they are referred to as cyclins A through I. Cyclin G is a direct transcriptional target of the p53 tumor suppressor gene product and thus functions downstream of p53. GAK is an association partner of cyclin G and CDK5. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

GeneReviews ResearchGenerating clinical summary…

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.41

LOEUF

GOF

Mechanism· predicted

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GeneReview available — GAK