STK25
Chr 2serine/threonine kinase 25
Also known as: SOK1, YSK1
STK25 encodes an oxidant stress-activated serine/threonine kinase that regulates protein transport at the Golgi apparatus, cell polarity, and migration, and functions as part of STRIPAK complexes that control multiple signaling pathways including Hippo, MAPK, and cytoskeleton remodeling. Mutations cause autosomal recessive primary microcephaly with seizures and intellectual disability. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.533), suggesting some tolerance to reduced gene dosage.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
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.
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
216 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 92 | 0 | 92 |
Likely Pathogenic | 0 | 0 | 13 | 0 | 13 |
VUS | 0 | 77 | 15 | 0 | 92 |
Likely Benign | 0 | 1 | 0 | 3 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 78 | 120 | 3 | 201 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
STK25 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools