PLK4

Chr 4AR

polo like kinase 4

Also known as: MCCRP2, SAK, STK18

NCBI Gene: 10733 ENSG00000142731 UniProt: O00444 OMIM: 605031

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the polo family of serine/threonine protein kinases. The protein localizes to centrioles, complex microtubule-based structures found in centrosomes, and regulates centriole duplication during the cell cycle. Three alternatively spliced transcript variants that encode different protein isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.571 OMIM phenotype

Clinical Summary— PLK4

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

34 unique Pathogenic / Likely Pathogenic· 367 VUS of 730 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.000

Z-score 3.85

OE 0.38 (0.26–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.80Z-score

OE missense 0.90 (0.83–0.97)

447 obs / 497.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.26–0.57)

0≤0.351.4

Missense OE?0.90 (0.83–0.97)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

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

This gene — mechanism propensity

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

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

730 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23

Likely Pathogenic11

VUS367

Likely Benign258

Benign32

Conflicting14

Pathogenic

Likely Pathogenic

367

VUS

258

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	22	0	1	0	23
Likely Pathogenic	11	0	0	0	11
VUS	4	335	23	5	367
Likely Benign	0	9	104	145	258
Benign	0	4	20	8	32
Conflicting	—				14
Total	37	348	148	158	705

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

29 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap PLK4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →