PLK1

Chr 16

polo like kinase 1

Also known as: PLK, STPK13

NCBI Gene: 5347ENSG00000166851UniProt: P53350

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]

98
ClinVar variants
30
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
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
30 Pathogenic / Likely Pathogenic· 67 VUS of 98 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.05–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.57–0.71)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 3 / 25.0Missense obs/exp: 241 / 379.3Syn Z: 0.13

ClinVar Variant Classifications

98 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic3
VUS67
Benign1
27
Pathogenic
3
Likely Pathogenic
67
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
3
0
3
VUS
0
61
6
0
67
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Total06136198

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

View in ClinVar →

Protein Context — Lollipop Plot

PLK1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
POLO-LIKE KINASE 1; PLK1
MIM #602098 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Polo-like kinase 1 (PLK1) signaling in cancer and beyond.
Iliaki S et al.·Biochem Pharmacol
2021Review
Targeting Plk1 Sensitizes Pancreatic Cancer to Immune Checkpoint Therapy.
Zhang Z et al.·Cancer Res
2022
Single-cell analyses reveal evolution mimicry during the specification of breast cancer subtype.
Gao ZJ et al.·Theranostics
2024
Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer.
Shi W et al.·Nat Commun
2021
Combining exome/genome sequencing with data repository analysis reveals novel gene-disease associations for a wide range of genetic disorders.
Bertoli-Avella AM et al.·Genet Med
2021
DLGAP5 promotes lung adenocarcinoma growth via upregulating PLK1 and serves as a therapeutic target.
Chen M et al.·J Transl Med
2024
The Novel ATR Inhibitor M1774 Induces Replication Protein Overexpression and Broad Synergy with DNA-targeted Anticancer Drugs.
Jo U et al.·Mol Cancer Ther
2024
Invasive FoxM1 phosphorylated by PLK1 induces the polarization of tumor-associated macrophages to promote immune escape and metastasis, amplified by IFITM1.
Xu R et al.·J Exp Clin Cancer Res
2023
Clinical considerations for the design of PROTACs in cancer.
Nieto-Jiménez C et al.·Mol Cancer
2022Review
Polo-like kinases and acute leukemia.
Goroshchuk O et al.·Oncogene
2019Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
An integrative multi-omics analysis leveraging Mendelian randomization and subsequent experimental validation prioritizes glutathione S-transferase mu 5 (GSTM5) as a genomic stability-related gene and a therapeutic vulnerability to PLK1 inhibition in breast cancer.
Ma H et al.·Int J Biol Macromol
2026
Dysregulated TMPO-AS1/let-7b-5p/PLK1/E2F1 Axis Associated with Poor Prognosis in Lung Adenocarcinoma.
Baweja B et al.·Asian Pac J Cancer Prev
2026
Synergistic Anticancer Effects of the PLK1 Inhibitor BI-2536 and β-Glucan in Colon and Gastric Cancer Cells.
Takci RG et al.·Anticancer Res
2026
Methadone maintenance therapy alters the expression of PLK1 and IFIH1 in patients with heroin addiction: a case-control study.
Zhang B et al.·Psychopharmacology (Berl)
2026Cohort
FAM216A Promotes Hepatocellular Carcinoma Proliferation and Invasion through the PLK1/ERK Signaling Pathway.
Ma P et al.·Genet Test Mol Biomarkers
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools