STK3

Chr 8

serine/threonine kinase 3

Also known as: KRS1, MST2

NCBI Gene: 6788ENSG00000104375UniProt: Q9Y6E0OMIM: 605030

The protein is a serine/threonine kinase that promotes apoptosis in response to stress stimuli and regulates cellular migration, axon regeneration, and multiple signaling pathways including Hippo and MAPK. Mutations cause autosomal recessive primary microcephaly with seizures and developmental delay. The gene shows very low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected patients.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.87
Clinical Summary— STK3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 111 VUS of 169 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.000
Z-score 2.06
OE 0.56 (0.37–0.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.58Z-score
OE missense 0.73 (0.65–0.82)
194 obs / 266.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.37–0.87)
0≤0.351.4
Missense OE0.73 (0.65–0.82)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 14 / 25.1Missense obs/exp: 194 / 266.4Syn Z: 0.58
DN
0.80top 25%
GOF
0.74top 25%
LOF
0.2873th %ile

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.

DNprediction above median
GOFprediction above median

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

169 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
VUS111
Likely Benign2
Benign2
35
Pathogenic
111
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
0
0
0
VUS
0
98
13
0
111
Likely Benign
0
1
0
1
2
Benign
0
1
0
1
2
Total0100482150

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

View in ClinVar →

Protein Context — Lollipop Plot

STK3 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
STK3 promotes gastric carcinogenesis by activating Ras-MAPK mediated cell cycle progression and serves as an independent prognostic biomarker
Chen B et al.·Mol Cancer
2021
Targeting the Divergent Roles of STK3 Inhibits Breast Cancer Cell Growth and Opposes Doxorubicin-Induced Cardiotoxicity In Vitro
Nam J et al.·Cancers (Basel)
2023
Inhibitors of the Hippo Pathway Kinases STK3/MST2 and STK4/MST1 Have Utility for the Treatment of Acute Myeloid Leukemia
Bata N et al.·J Med Chem
2022
Serine/Threonine Protein Kinase-3 Promotes Oral Squamous Cell Carcinoma by Activating Ras-MAPK Mediated Cell Cycle Progression
Yue L et al.·Int J Gen Med
2023
STK3-ALK, a Novel ALK Rearrangement in Non-Small Cell Lung Cancer With Sensitivity to Tyrosine Kinase Inhibitors: A Case Report
Feng C et al.·Front Oncol
2021Case report
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Extracellular vesicles derived from hADSCs rescue acute pancreatitis by carrying p-STK3 to regulate Treg differentiation.
Xie R et al.·iScience
2026Open Access
Multi-omics characterization of benzo[a]pyrene toxicity networks identifies SERPINE1 and STK3 as prognostic biomarkers and therapeutic targets in head and neck squamous cell carcinoma.
Guo Y et al.·Naunyn Schmiedebergs Arch Pharmacol
2026
STK3 is a transcriptional target of YAP1 and a hub component in the crosstalk between Hippo and Wnt signaling pathways during gastric carcinogenesis.
Xie F et al.·Mol Cancer
2025Open Access
Exploring STK3 in melanoma: a systematic review of signaling networks and therapeutic opportunities.
Khanahmadi M et al.·Mol Biol Rep
2024Review
Identification of a novel alternative splicing isoform of the Hippo kinase STK3/MST2 with impaired kinase and cell growth suppressing activities.
Rodrigues AM et al.·Oncogene
2024
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