GSPT1

Chr 16

G1 to S phase transition 1

Also known as: 551G9.2, ETF3A, GST1, eRF3a

GSPT1 encodes a GTPase that mediates translation termination at stop codons and is a component of the nonsense-mediated decay pathway that eliminates aberrant mRNAs. Mutations cause autosomal dominant neurodevelopmental disorder with intellectual disability, seizures, and movement abnormalities. This gene is highly constrained against loss-of-function variants, indicating intolerance to haploinsufficiency.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.16
Clinical SummaryGSPT1
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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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 4.88
OE 0.03 (0.010.16)
Highly constrained

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

Missense Constraint
3.32Z-score
OE missense 0.48 (0.420.55)
152 obs / 318.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.03 (0.010.16)
00.351.4
Missense OE0.48 (0.420.55)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 1 / 29.7Missense obs/exp: 152 / 318.7Syn Z: -0.25
DN
0.3495th %ile
GOF
0.5072th %ile
LOF
0.69top 10%

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

LOFprediction above median · LOEUF 0.16

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

GSPT1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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