PDPK1

Chr 16

3-phosphoinositide dependent protein kinase 1

Also known as: PDK1, PRO0461

NCBI Gene: 5170 ENSG00000140992 UniProt: O15530 OMIM: 605213

The protein encoded by this gene is a master serine/threonine kinase that phosphorylates and activates multiple AGC family kinases including AKT, playing a central role in insulin signaling and controlling cell proliferation, survival, glucose uptake, and cardiac homeostasis. Mutations cause a neurodevelopmental disorder with early infantile epileptic encephalopathy and focal cortical dysplasia, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.29), indicating intolerance to haploinsufficiency in the general population.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Enables 3-phosphoinositide-dependent protein kinase activity; phospholipase activator activity; and phospholipase binding activity. Involved in several processes, including cell surface receptor signaling pathway; intracellular signaling cassette; and regulation of signal transduction. Acts upstream of or within intracellular signal transduction. Located in cell projection; cytosol; and plasma membrane. Implicated in prostate cancer. Biomarker of lung non-small cell carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM 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)

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P/LP submissions

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P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· predicted

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GeneReview available — PDPK1