STOX2

Chr 4

storkhead box 2

NCBI Gene: 56977 ENSG00000173320 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…

LOFmechanismLOEUF 0.42

Clinical Summary— STOX2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

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ClinVar Variants

119 VUS of 136 total submissions

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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

This gene — mechanism propensity

0.4884th %ile

GOF

0.6150th %ile

LOF

0.64top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.42

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

136 submitted variants in ClinVar

ClinVar

Classification Summary

VUS119

Likely Benign4

119

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	119	0	119
Likely Benign	3	1	4
Benign	0	0	0
Total	122	1	123

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

View in ClinVar →

103 pathogenic / likely-pathogenic (of 115) ClinVar copy-number / structural variants overlap STOX2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →