PLK3

Chr 1

polo like kinase 3

Also known as: CNK, FNK, PLK-3, PRK

NCBI Gene: 1263ENSG00000173846UniProt: Q9H4B4OMIM: 602913

PLK3 encodes a serine/threonine kinase that regulates cell cycle progression, DNA damage response, and cellular stress responses by phosphorylating multiple target proteins including p53, CDC25A, and CHEK2. The gene is highly constrained against loss-of-function variants (pLI near 1.0), indicating that haploinsufficiency is likely not tolerated in humans. Pathogenic variants in PLK3 have not yet been established as a cause of human disease, despite the protein's critical cellular functions.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.71
Clinical Summary— PLK3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
2 unique Pathogenic / Likely Pathogenic· 74 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.71LOEUF
pLI 0.000
Z-score 2.83
OE 0.46 (0.31–0.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.24Z-score
OE missense 0.82 (0.75–0.90)
318 obs / 386.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.46 (0.31–0.71)
0≤0.351.4
Missense OE0.82 (0.75–0.90)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 15 / 32.4Missense obs/exp: 318 / 386.5Syn Z: -0.12
DN
0.6938th %ile
GOF
0.6345th %ile
LOF
0.3261th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic1
VUS74
Likely Benign3
1
Pathogenic
1
Likely Pathogenic
74
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
1
0
1
VUS
0
73
1
0
74
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total0753179

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

View in ClinVar →

Protein Context — Lollipop Plot

PLK3 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients