STK40

Chr 1

serine/threonine kinase 40

Also known as: SHIK, SgK495

NCBI Gene: 83931ENSG00000196182UniProt: Q8N2I9

Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in regulation of MAPK cascade. Predicted to act upstream of or within several processes, including glycogen metabolic process; lung development; and respiratory system process. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

88
ClinVar variants
8
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
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.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 58 VUS of 88 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.23LOEUF
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?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.
1.46Z-score
OE missense 0.76 (0.68–0.85)
218 obs / 287.8 exp
Tolerant

Mild missense constraint

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.0.05 (0.02–0.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.68–0.85)
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.0.87
0≤1.21.6
LoF obs/exp: 1 / 20.9Missense obs/exp: 218 / 287.8Syn Z: 1.18

ClinVar Variant Classifications

88 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS58
Likely Benign5
Benign2
6
Pathogenic
2
Likely Pathogenic
58
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
54
4
0
58
Likely Benign
0
3
0
2
5
Benign
0
0
0
2
2
Total05712473

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

View in 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.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
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
2025🔓 Open Access
Pseudokinase STK40 promotes TH1 and TH17 cell differentiation by targeting FOXO transcription factors.
Tao Y et al.·Sci Adv
2024🔓 Open Access
STK40 inhibits trophoblast fusion by mediating COP1 ubiquitination to degrade P57Kip2.
Li X et al.·J Transl Med
2024🔓 Open 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
2023🔓 Open AccessCohort
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