STK40

Chr 1

serine/threonine kinase 40

Also known as: SHIK, SgK495

NCBI Gene: 83931ENSG00000196182UniProt: Q8N2I9OMIM: 609437

STK40 encodes a serine/threonine kinase that binds ATP and may negatively regulate NF-kappa-B and p53-mediated gene transcription. Mutations cause autosomal recessive primary ciliary dyskinesia with defects in ciliary structure and function, leading to chronic respiratory infections, bronchiectasis, and situs inversus. The gene is highly constrained against loss-of-function variation (pLI 0.996, LOEUF 0.227), reflecting its essential role in ciliary function.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.23
Clinical Summary— STK40
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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
0.23LOEUF
pLI 0.996
Z-score 4.03
OE 0.05 (0.02–0.23)
Highly constrained

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

Missense Constraint
1.46Z-score
OE missense 0.76 (0.68–0.85)
218 obs / 287.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.05 (0.02–0.23)
0≤0.351.4
Missense OE0.76 (0.68–0.85)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 1 / 20.9Missense obs/exp: 218 / 287.8Syn Z: 1.18
DN
0.4090th %ile
GOF
0.4579th %ile
LOF
0.70top 10%

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

LOFprediction above median · LOEUF 0.23

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

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

STK40 · 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.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Pseudokinase STK40 limits T cell exhaustion through COP1-dependent degradation of AP1-family transcription factors.
Altshuler-Keylin S et al.·Nat Immunol
2025
Integrative High-Throughput RNAi Screening Identifies BRSK1, STK32C and STK40 as Novel Activators of YAP/TAZ.
Gill MK et al.·Int J Mol Sci
2025Open Access
Pseudokinase STK40 promotes TH1 and TH17 cell differentiation by targeting FOXO transcription factors.
Tao Y et al.·Sci Adv
2024Open Access
STK40 inhibits trophoblast fusion by mediating COP1 ubiquitination to degrade P57Kip2.
Li X et al.·J Transl Med
2024Open Access
Construction and validation of a novel senescence-related risk score can help predict the prognosis and tumor microenvironment of gastric cancer patients and determine that STK40 can affect the ROS accumulation and proliferation ability of gastric cancer cells.
Sun W et al.·Front Immunol
2023Open AccessCohort
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