PLK1

Chr 16

polo like kinase 1

Also known as: PLK, STPK13

NCBI Gene: 5347 ENSG00000166851 UniProt: P53350 OMIM: 602098

PLK1 encodes a serine/threonine kinase that regulates multiple critical functions during mitosis including centrosome maturation, spindle assembly, chromosome cohesion, and cytokinesis. Mutations in PLK1 cause an autosomal dominant neurodevelopmental disorder characterized by microcephaly, intellectual disability, and seizures with onset in infancy or early childhood. This gene is highly constrained against loss-of-function variants, indicating that even single functional copies are insufficient for normal development.

OMIM ResearchSummary from RefSeq, UniProt

The Ser/Thr protein kinase encoded by this gene belongs to the CDC5/Polo subfamily. It is highly expressed during mitosis and elevated levels are found in many different types of cancer. Depletion of this protein in cancer cells dramatically inhibited cell proliferation and induced apoptosis; hence, it is a target for cancer therapy. [provided by RefSeq, Sep 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.31

Clinical Summary— PLK1

⚡

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.

📋

ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 62 VUS of 81 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.979

Z-score 4.08

OE 0.12 (0.05–0.31)

Highly constrained

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

Missense Constraint?

2.52Z-score

OE missense 0.64 (0.57–0.71)

241 obs / 379.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.12 (0.05–0.31)

0≤0.351.4

Missense OE?0.64 (0.57–0.71)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 3 / 25.0Missense obs/exp: 241 / 379.3Syn Z: 0.13

This gene — mechanism propensity

0.3892th %ile

GOF

0.4579th %ile

LOF

0.67top 25%

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

LOFprediction above median · LOEUF 0.31

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

81 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS62

Benign1

Pathogenic

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	0	0	0	0
VUS	1	61	0	0	62
Likely Benign	0	0	0	0	0
Benign	0	0	0	1	1
Total	1	61	1	1	64

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap PLK1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →