G3BP2

Chr 4

G3BP stress granule assembly factor 2

NCBI Gene: 9908 ENSG00000138757 UniProt: Q9UN86 OMIM: 620020

The G3BP2 protein serves as a scaffold for cytoplasmic stress granule formation, which are membraneless compartments that store mRNAs and proteins in response to cellular stress and function as platforms for antiviral signaling. Mutations in this gene cause neurodevelopmental disorders with onset in infancy or early childhood, featuring developmental delay, intellectual disability, seizures, and brain malformations, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, indicating that proper protein function is critical for normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables molecular condensate scaffold activity. Involved in positive regulation of stress granule assembly; protein homooligomerization; and stress granule assembly. Located in cytoplasmic stress granule and cytosol. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.18

Clinical Summary— G3BP2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

28 VUS of 47 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.18LOEUF

pLI 1.000

Z-score 4.59

OE 0.04 (0.01–0.18)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.61Z-score

OE missense 0.40 (0.34–0.47)

113 obs / 284.2 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.18)

0≤0.351.4

Missense OE?0.40 (0.34–0.47)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 1 / 26.5Missense obs/exp: 113 / 284.2Syn Z: 1.02

This gene — mechanism propensity

0.18100th %ile

GOF

0.2597th %ile

LOF

0.84top 5%

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

LOFprediction above median · LOEUF 0.18

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

47 submitted variants in ClinVar

ClinVar

Classification Summary

VUS28

Likely Benign2

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	28	0	28
Likely Benign	1	1	2
Benign	0	0	0
Total	29	1	30

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap G3BP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →