EIF4A1

Chr 17

eukaryotic translation initiation factor 4A1

Also known as: DDX2A, EIF-4A, EIF4A, eIF-4A-I, eIF4A-I

NCBI Gene: 1973ENSG00000161960UniProt: P60842OMIM: 602641

The protein is an ATP-dependent RNA helicase that is essential for translation initiation, functioning as part of the eIF4F complex to unwind RNA secondary structures in mRNA 5'-UTRs and enable ribosome binding. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and seizures. This gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.12), indicating that functional copies are essential for normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.12
Clinical Summary— EIF4A1
⚡
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
20 unique Pathogenic / Likely Pathogenic· 23 VUS of 47 total submissions
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
0.12LOEUF
pLI 1.000
Z-score 4.67
OE 0.00 (0.00–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.93Z-score
OE missense 0.30 (0.25–0.36)
74 obs / 248.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.12)
0≤0.351.4
Missense OE0.30 (0.25–0.36)
0≤0.61.4
Synonymous OE1.55
0≤1.21.6
LoF obs/exp: 0 / 25.4Missense obs/exp: 74 / 248.2Syn Z: -4.09
DN
0.3693th %ile
GOF
0.3392th %ile
LOF
0.74top 10%

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

LOFprediction above median · LOEUF 0.12

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

47 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS23
Likely Benign2
Benign1
19
Pathogenic
1
Likely Pathogenic
23
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
1
0
1
VUS
1
12
10
0
23
Likely Benign
0
1
0
1
2
Benign
0
0
0
1
1
Total11330246

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

View in ClinVar →

Protein Context — Lollipop Plot

EIF4A1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Eukaryotic translation initiation factor 4A1 in the pathogenesis and treatment of cancers
Huang J et al.·Front Mol Biosci
2023
Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming
Wu KL et al.·Biology (Basel)
2022
eIF4A1-dependent mRNAs employ purine-rich 5'UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation
Schmidt T et al.·Nucleic Acids Res
2023
Translation element EIF4A1 is a potential divergent immune biomarker between colon cancer and rectal cancer
Zhu Z et al.·Int J Immunopathol Pharmacol
2025
Targeted intervention of eIF4A1 inhibits EMT and metastasis of pancreatic cancer cells via c-MYC/miR-9 signaling
Zhao Y et al.·Cancer Cell Int
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients