G3BP2

Chr 4

G3BP stress granule assembly factor 2

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.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.18
Clinical SummaryG3BP2
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.
📋
ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 32 VUS of 74 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 4.59
OE 0.04 (0.010.18)
Highly constrained

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

Missense Constraint
3.61Z-score
OE missense 0.40 (0.340.47)
113 obs / 284.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.04 (0.010.18)
00.351.4
Missense OE0.40 (0.340.47)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 1 / 26.5Missense obs/exp: 113 / 284.2Syn Z: 1.02
DN
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

74 submitted variants in ClinVar

Classification Summary

Pathogenic23
VUS32
Likely Benign2
23
Pathogenic
32
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
0
0
0
VUS
0
28
4
0
32
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total02927157

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

View in ClinVar →

Protein Context — Lollipop Plot

G3BP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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