PLK4

Chr 4AR

polo like kinase 4

Also known as: MCCRP2, SAK, STK18

The protein is a serine/threonine kinase that localizes to centrioles and regulates centriole duplication during the cell cycle. Mutations cause microcephaly and chorioretinopathy, autosomal recessive, 2, following an autosomal recessive inheritance pattern. The pathogenic mechanism involves dominant negative effects.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.571 OMIM phenotype
Clinical SummaryPLK4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.000
Z-score 3.85
OE 0.38 (0.260.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.80Z-score
OE missense 0.90 (0.830.97)
447 obs / 497.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.260.57)
00.351.4
Missense OE0.90 (0.830.97)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 17 / 44.8Missense obs/exp: 447 / 497.2Syn Z: -1.31
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePLK4-related microcephaly, growth failure and retinopathyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7034th %ile
GOF
0.4481th %ile
LOF
0.4136th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PLK4 · 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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