STK40

Chr 1

serine/threonine kinase 40

Also known as: SHIK, SgK495

NCBI Gene: 83931 ENSG00000196182 UniProt: Q8N2I9 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.23

Clinical Summary— STK40

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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.

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ClinVar Variants

55 VUS of 77 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?

0.23LOEUF

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 OE?0.05 (0.02–0.23)

0≤0.351.4

Missense OE?0.76 (0.68–0.85)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 1 / 20.9Missense obs/exp: 218 / 287.8Syn Z: 1.18

This gene — mechanism propensity

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

77 submitted variants in ClinVar

ClinVar

Classification Summary

VUS55

Likely Benign5

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	55	0	55
Likely Benign	3	2	5
Benign	0	2	2
Total	58	4	62

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap STK40 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →