EIF4A1

Chr 17

eukaryotic translation initiation factor 4A1

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

NCBI Gene: 1973ENSG00000161960UniProt: P60842

Enables double-stranded RNA binding activity and translation initiation factor activity. Involved in cytoplasmic translational initiation and positive regulation of transcription by RNA polymerase II. Located in nuclear stress granule; perinuclear region of cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

46
ClinVar variants
20
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
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 Pathogenic / Likely Pathogenic· 23 VUS of 46 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.
0.12LOEUF
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?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.
3.93Z-score
OE missense 0.30 (0.25–0.36)
74 obs / 248.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?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.0.00 (0.00–0.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.30 (0.25–0.36)
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.1.55
0≤1.21.6
LoF obs/exp: 0 / 25.4Missense obs/exp: 74 / 248.2Syn Z: -4.09

ClinVar Variant Classifications

46 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
0
12
11
0
23
Likely Benign
0
1
0
1
2
Benign
0
0
0
1
1
Total01331246

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeting PGE2 mediated senescent neuron improves tumor therapy.
Zhao J et al.·Neuro Oncol
2025
Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis.
Lizardo MM et al.·Clin Cancer Res
2024
Genomic landscape of virus-associated cancers.
Nam Y et al.·Nat Commun
2025
Role of eIF4A1 in triple-negative breast cancer stem-like cell-mediated drug resistance.
Raman D et al.·Cancer Rep (Hoboken)
2022
Differential Regulation of the Melanoma Proteome by eIF4A1 and eIF4E.
Joyce CE et al.·Cancer Res
2017
Blocking NRF2 Translation by Inhibition of Cap-Dependent Initiation Sensitizes Lymphoma Cells to Ferroptosis and CAR T-cell Immunotherapy.
Manara P et al.·Cancer Res
2025
TOPK Inhibition Promotes Anti-Tumor Immunity Via eIF4F Complex Mediated STAT1 Translation in Gastric Cancer.
Chen J et al.·Adv Sci (Weinh)
2026
Novel eIF4A1 inhibitors with anti-tumor activity in lymphoma.
Kayastha F et al.·Mol Med
2022
The malignant phenotype in breast cancer is driven by eIF4A1-mediated changes in the translational landscape.
Modelska A et al.·Cell Death Dis
2015
CRISPR/Cas9-based discovery of ccRCC therapeutic opportunities through molecular mechanism and immune microenvironment analysis.
Han B et al.·Front Immunol
2025Functional
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools