ETF1

Chr 5

eukaryotic translation termination factor 1

Also known as: D5S1995, ERF, ERF1, RF1, SUP45L1, TB3-1

NCBI Gene: 2107ENSG00000120705UniProt: P62495

This gene encodes a class-1 polypeptide chain release factor. The encoded protein plays an essential role in directing termination of mRNA translation from the termination codons UAA, UAG and UGA. This protein is a component of the SURF complex which promotes degradation of prematurely terminated mRNAs via the mechanism of nonsense-mediated mRNA decay (NMD). Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 6, 7, and X. [provided by RefSeq, Aug 2013]

26
ClinVar variants
12
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ETF1
⚡
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
12 Pathogenic / Likely Pathogenic· 13 VUS of 26 total submissions

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.
0.25LOEUF
pLI 0.996
Z-score 4.27
OE 0.08 (0.03–0.25)
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.
4.39Z-score
OE missense 0.19 (0.15–0.25)
45 obs / 234.1 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.0.08 (0.03–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.19 (0.15–0.25)
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.0.96
0≤1.21.6
LoF obs/exp: 2 / 25.1Missense obs/exp: 45 / 234.1Syn Z: 0.27

ClinVar Variant Classifications

26 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS13
Likely Benign1
11
Pathogenic
1
Likely Pathogenic
13
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
1
0
1
VUS
1
6
6
0
13
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total1619026

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

View in ClinVar →

Protein Context — Lollipop Plot

ETF1 · 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
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Integrated phenotypic screening and chemical proteomics identifies ETF1 ligands that modulate viral translation and replication.
Kim AS et al.·Proc Natl Acad Sci U S A
2026🔓 Open Access
KDM3B-ETF1 fusion gene downregulates LMO2 via the WNT/β-catenin signaling pathway, promoting metastasis of invasive ductal carcinoma.
Hu A et al.·Cancer Gene Ther
2022
Novel PtdIns(3)P-binding protein Etf1 functions as an effector of the Vps34 PtdIns 3-kinase in autophagy.
Wurmser AE et al.·J Cell Biol
2002🔓 Open Access
Evaluation of ETF1/eRF1, mapping to 5q31, as a candidate myeloid tumor suppressor gene.
Dubourg C et al.·Cancer Genet Cytogenet
2002
Eukaryotic translation termination factor gene (ETF1/eRF1) maps at D5S500 in a commonly deleted region of chromosome 5q31 in malignant myeloid diseases.
Guenet L et al.·Cytogenet Cell Genet
2000
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools