STK3

Chr 8

serine/threonine kinase 3

Also known as: KRS1, MST2

This gene encodes a serine/threonine protein kinase activated by proapoptotic molecules indicating the encoded protein functions as a growth suppressor. Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

0
Active trials
11
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.87
LOEUF
Multiple*
Mechanism· predicted
Clinical SummarySTK3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.000
Z-score 2.06
OE 0.56 (0.370.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.58Z-score
OE missense 0.73 (0.650.82)
194 obs / 266.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.370.87)
00.351.4
Missense OE0.73 (0.650.82)
00.61.4
Synonymous OE0.92
01.21.6
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

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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