GSPT1

Chr 16

G1 to S phase transition 1

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

NCBI Gene: 2935 ENSG00000103342 UniProt: P15170 OMIM: 139259

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables GTPase activity and translation release factor activity. Involved in regulation of translational termination and translational termination. Acts upstream of or within protein methylation. Part of translation release factor complex. Is active in cytosolic ribosome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.16

Clinical Summary— GSPT1

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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

71 VUS of 94 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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?

0.16LOEUF

pLI 1.000

Z-score 4.88

OE 0.03 (0.01–0.16)

Highly constrained

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

Missense Constraint?

3.32Z-score

OE missense 0.48 (0.42–0.55)

152 obs / 318.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.16)

0≤0.351.4

Missense OE?0.48 (0.42–0.55)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 1 / 29.7Missense obs/exp: 152 / 318.7Syn Z: -0.25

This gene — mechanism propensity

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

94 submitted variants in ClinVar

ClinVar

Classification Summary

VUS71

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	71	71
Likely Benign	1	1
Benign	0	0
Total	72	72

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap GSPT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →