STK24

Chr 13

serine/threonine kinase 24

Also known as: HEL-S-95, MST3, MST3B, STE20, STK3

NCBI Gene: 8428 ENSG00000102572 UniProt: Q9Y6E0 OMIM: 604984

This gene encodes a serine/threonine protein kinase that regulates apoptosis, cell migration, and axon regeneration, and functions as part of STRIPAK complexes that control multiple signaling pathways including MAPK and Hippo signaling. Mutations cause autosomal recessive cerebellar ataxia, developmental delay, and seizures with childhood onset. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.58), primarily affecting the central nervous system.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a serine/threonine protein kinase that functions upstream of mitogen-activated protein kinase (MAPK) signaling. The encoded protein is cleaved into two chains by caspases; the N-terminal fragment (MST3/N) translocates to the nucleus and promotes programmed cells death. There is a pseudogene for this gene on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.58

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.58LOEUF

pLI 0.011

Z-score 3.13

OE 0.32 (0.19–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.99Z-score

OE missense 0.65 (0.57–0.74)

164 obs / 253.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.32 (0.19–0.58)

0≤0.351.4

Missense OE?0.65 (0.57–0.74)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 8 / 24.9Missense obs/exp: 164 / 253.3Syn Z: 0.50

Background carrier burden — how many people carry a rare variant somewhere in STK24?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

463 rare PASS variants

Rare truncating (LoF)

1 in 4,600

48 rare PASS variants

Rare synonymous (reference)

1 in 180

233 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for STK24. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 6,300
South Asian	~43k	1 in 120	1 in 5,300
Remaining (unassigned)	~30k	1 in 200	≈ 1 in 30,000
European (Finnish)	~27k	1 in 580	1 in 5,300
Admixed American	~22k	1 in 160	1 in 2,300
African / African American	~21k	1 in 110	1 in 2,900
East Asian	~20k	1 in 160	≈ 1 in 4,500
Ashkenazi Jewish	~13k	≈ 1 in 4,000	1 in 1,700
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 11 coding exons well covered in gnomAD exomes; exons 1, 3 marginal. Genomes: all 11.? see exons ↓