STOX2

Chr 4

storkhead box 2

NCBI Gene: 56977 ENSG00000173320 UniProt: Q9P2F5 OMIM: 617359

The protein contains a Storkhead-box winged-helix domain and is differentially expressed in decidual tissue. Mutations in this gene cause autosomal recessive developmental and epileptic encephalopathy with microcephaly and growth restriction, typically with onset in infancy or early childhood. The gene shows high constraint against loss-of-function variants (LOEUF 0.425), suggesting intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq

This gene encodes a Storkhead-box_winged-helix domain containing protein. This protein is differentially expressed in decidual tissue and may be involved in the susceptibility to pre-eclampsia with fetal growth restriction. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

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

0.42

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.484

Z-score 3.84

OE 0.22 (0.12–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.33Z-score

OE missense 0.84 (0.77–0.91)

446 obs / 532.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.12–0.42)

0≤0.351.4

Missense OE?0.84 (0.77–0.91)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 6 / 27.8Missense obs/exp: 446 / 532.5Syn Z: -0.54

Background carrier burden — how many people carry a rare variant somewhere in STOX2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 61

1,270 rare PASS variants

Rare truncating (LoF)

1 in 1,000

99 rare PASS variants

Rare synonymous (reference)

1 in 58

569 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for STOX2. 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 62	1 in 1,400
South Asian	~43k	1 in 45	1 in 160
Remaining (unassigned)	~30k	1 in 50	1 in 940
European (Finnish)	~27k	1 in 130	1 in 1,500
Admixed American	~22k	1 in 37	1 in 310
African / African American	~21k	1 in 39	1 in 1,100
East Asian	~20k	1 in 47	1 in 1,100
Ashkenazi Jewish	~13k	1 in 330	1 in 490
Middle Eastern	~2,884	1 in 48	1 in 320

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓