GSPT2

Chr X

G1 to S phase transition 2

Also known as: ERF3B, GST2

The protein is a GTPase that forms a complex with eukaryotic release factor 1 to mediate translation termination at stop codons and plays a role in nonsense-mediated mRNA decay. Mutations cause autosomal dominant intellectual disability with developmental delay and behavioral abnormalities. This gene is highly constrained against loss-of-function variants (pLI = 0.98, LOEUF = 0.24), indicating that haploinsufficiency is likely not tolerated in the general population.

Summary from RefSeq, UniProt
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0
Active trials
2
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.24
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical SummaryGSPT2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.983
Z-score 3.27
OE 0.00 (0.000.24)
Highly constrained

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

Missense Constraint
2.49Z-score
OE missense 0.55 (0.480.64)
133 obs / 242.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.24)
00.351.4
Missense OE0.55 (0.480.64)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 0 / 12.4Missense obs/exp: 133 / 242.0Syn Z: 0.64
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedGSPT2-related intellectual disabilityLOFXLR
DN
0.3395th %ile
GOF
0.4678th %ile
LOF
0.70top 10%

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

LOFprediction above median · LOEUF 0.24

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GSPT2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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