EEF1A1

Chr 6

eukaryotic translation elongation factor 1 alpha 1

Also known as: CCS-3, CCS3, EE1A1, EEF-1, EEF1A, EF-Tu, EF1A, EF1A1

NCBI Gene: 1915ENSG00000156508UniProt: P68104

This gene encodes an isoform of the alpha subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This isoform (alpha 1) is expressed in brain, placenta, lung, liver, kidney, and pancreas, and the other isoform (alpha 2) is expressed in brain, heart and skeletal muscle. This isoform is identified as an autoantigen in 66% of patients with Felty syndrome. This gene has been found to have multiple copies on many chromosomes, some of which, if not all, represent different pseudogenes. [provided by RefSeq, Jul 2008]

34
ClinVar variants
14
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— EEF1A1
⚡
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.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 16 VUS of 34 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.
0.29LOEUF
pLI 0.979
Z-score 3.50
OE 0.06 (0.02–0.29)
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.
3.72Z-score
OE missense 0.35 (0.29–0.41)
90 obs / 258.4 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.0.06 (0.02–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.35 (0.29–0.41)
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.1.70
0≤1.21.6
LoF obs/exp: 1 / 16.2Missense obs/exp: 90 / 258.4Syn Z: -5.29

ClinVar Variant Classifications

34 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic1
VUS16
Likely Benign1
Benign3
13
Pathogenic
1
Likely Pathogenic
16
VUS
1
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
1
0
1
VUS
0
13
3
0
16
Likely Benign
0
0
0
1
1
Benign
0
0
1
2
3
Total01318334

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

View in ClinVar →

Protein Context — Lollipop Plot

EEF1A1 · 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
Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma.
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu et al.·Cell
2017
Selective translation of nuclear mitochondrial respiratory proteins reprograms succinate metabolism in AML development and chemoresistance.
Han G et al.·Cell Stem Cell
2024
UCHL3 promotes hepatocellular carcinoma progression by stabilizing EEF1A1 through deubiquitination.
Zhao J et al.·Biol Direct
2024
Targeting TUBB2B inhibits triple-negative breast cancer growth and brain-metastatic colonization.
He Q et al.·J Exp Clin Cancer Res
2025
Analysis of the Expression and Subcellular Distribution of eEF1A1 and eEF1A2 mRNAs during Neurodevelopment.
Wefers Z et al.·Cells
2022
Small Molecule with Big Impact: Metarrestin Targets the Perinucleolar Compartment in Cancer Metastasis.
Kashyap VK et al.·Cells
2024Review
High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1-actin Complex as a New Potential Target for Therapy.
Bosutti A et al.·Int J Mol Sci
2022
eEF1A2 and neuronal degeneration.
Abbott CM et al.·Biochem Soc Trans
2009
Elongation factor 1A1 regulates metabolic substrate preference in mammalian cells.
Wilson RB et al.·J Biol Chem
2024
Deep multi-omics integration approach reveals new molecular features of uterine leiomyosarcoma.
Falcao RM et al.·Biochim Biophys Acta Mol Basis Dis
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Identification of EEF1A1 as a therapeutic target in TNBC: Anticancer action of a novel Penicillide-derived inhibitor through ribosomal protein regulation.
Yu J et al.·Bioorg Chem
2026
EIF4A3-Induced Circular RNA circSnd1 Promotes Muscle Atrophy and Muscle Ageing by Stabilizing EEF1A1.
Li J et al.·J Cachexia Sarcopenia Muscle
2026🔓 Open Access
Machine learning guided structural dynamics identifies translation elongation factor 1 (EEF1A1) as an immunological biomarker and marine natural products as therapeutic leads for rheumatoid arthritis with major depressive disorder.
Panchalingam S et al.·Comput Biol Med
2026
Discovery of a Covalent Small-Molecule eEF1A1 Inhibitor via Structure-Based Virtual Screening.
Deng Y et al.·J Chem Inf Model
2026
Loss of UFL1 confers enzalutamide resistance of prostate tumors by regulating METTL16-mediated m6A modification of EEF1A1 mRNA.
Wu X et al.·Int J Biol Sci
2026🔓 Open Access
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