GSPT1

Chr 16

G1 to S phase transition 1

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

NCBI Gene: 2935ENSG00000103342UniProt: P15170

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]

125
ClinVar variants
15
Pathogenic / LP
1.00
pLI score· haploinsufficient
2
Active trials
Clinical Summary— GSPT1
⚡
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
15 Pathogenic / Likely Pathogenic· 87 VUS of 125 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.03 (0.01–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.48 (0.42–0.55)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 1 / 29.7Missense obs/exp: 152 / 318.7Syn Z: -0.25

ClinVar Variant Classifications

125 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic1
VUS87
Likely Benign1
14
Pathogenic
1
Likely Pathogenic
87
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
1
0
1
VUS
0
71
16
0
87
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total072310103

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A novel cereblon modulator recruits GSPT1 to the CRL4(CRBN) ubiquitin ligase.
Matyskiela ME et al.·Nature
2016
CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells.
Surka C et al.·Blood
2021
A Dual-Target and Dual-Mechanism Design Strategy by Combining Inhibition and Degradation Together.
Liu Y et al.·J Am Chem Soc
2025Functional
Cancer Biology of GSPT1: Mechanisms and Targeted Therapy Opportunities of Molecular Glue Degraders.
Lin Q et al.·Adv Sci (Weinh)
2025Review
Potential of GSPT1 as a novel target for glioblastoma therapy.
Sasayama T et al.·Cell Death Dis
2024
GSPT1 degraders: research progress, development strategies and challenges.
Liu C et al.·Bioorg Med Chem
2025Review
The orally bioavailable GSPT1/2 degrader SJ6986 exhibits in vivo efficacy in acute lymphoblastic leukemia.
Chang Y et al.·Blood
2023
Targeting of IRAK4 and GSPT1 enhances therapeutic efficacy in AML via c-Myc destabilization.
Vick EJ et al.·Leukemia
2025
Design and Discovery of Preclinical Candidate LYG-409 as a Highly Potent and Selective GSPT1 Molecular Glue Degraders.
Zhang Y et al.·J Med Chem
2025
Proximity interactome analysis of Lassa polymerase reveals eRF3a/GSPT1 as a druggable target for host-directed antivirals.
Fang J et al.·Proc Natl Acad Sci U S A
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Hepatocellular Carcinoma (HCC)

Study of CT-01 as Monotherapy and Combination Therapy in Subjects With Intermediate or Advanced Hepatocellular Carcinoma

NOT YET RECRUITING
NCT06994572Phase PHASE1Captor Therapeutics S.A.Started 2025-05-26
CT-01EVEROLIMUS
NSCLCSCLCHigh Grade Neuroendocrine Cancer

Study of Oral MRT-2359 in Selected Cancer Patients

ACTIVE NOT RECRUITING
NCT05546268Phase PHASE1, PHASE2Monte Rosa Therapeutics, IncStarted 2022-10-12
Oral MRT-2359Oral MRT-2359Oral MRT-2359

External Resources

Links to major genomics databases and tools