PDPK1

Chr 16

3-phosphoinositide dependent protein kinase 1

Also known as: PDK1, PRO0461

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.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.29
Clinical SummaryPDPK1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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GeneReview available — PDPK1
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.980
Z-score 3.52
OE 0.06 (0.020.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.01Z-score
OE missense 0.56 (0.480.67)
95 obs / 168.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.020.29)
00.351.4
Missense OE0.56 (0.480.67)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 1 / 16.4Missense obs/exp: 95 / 168.4Syn Z: -0.30
DN
0.3693th %ile
GOF
0.4974th %ile
LOF
0.68top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PDPK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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