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 protein homooligomerization and stress granule assembly. Located in cytoplasmic stress granule and cytosol. [provided by Alliance of Genome Resources, Jun 2026]

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

0.18

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in G3BP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

387 rare PASS variants

Rare truncating (LoF)

1 in 6,300

44 rare PASS variants

Rare synonymous (reference)

1 in 580

171 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for G3BP2. 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 290	1 in 6,700
South Asian	~43k	1 in 290	1 in 2,400
Remaining (unassigned)	~30k	1 in 200	≈ 1 in 15,000
European (Finnish)	~27k	1 in 340	≈ 1 in 13,000
Admixed American	~22k	1 in 250	≈ 1 in 5,300
African / African American	~21k	1 in 220	≈ 1 in 6,100
East Asian	~20k	1 in 360	≈ 1 in 9,400
Ashkenazi Jewish	~13k	1 in 650	none seen
Middle Eastern	~2,884	1 in 320	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): 3 of 11 coding exons well covered in gnomAD exomes; exons 2, 3, 5, 6, 8 and 3 more marginal. Genomes: all 11.? see exons ↓