EIF4A1

Chr 17

eukaryotic translation initiation factor 4A1

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

NCBI Gene: 1973 ENSG00000161960 UniProt: P60842

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.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.12

Clinical Summary— EIF4A1

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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.

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ClinVar Variants

14 VUS of 18 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.00 (0.00–0.12)

0≤0.351.4

Missense OE?0.30 (0.25–0.36)

0≤0.61.4

Synonymous OE?1.55

0≤1.21.6

LoF obs/exp: 0 / 25.4Missense obs/exp: 74 / 248.2Syn Z: -4.09

This gene — mechanism propensity

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

18 submitted variants in ClinVar

ClinVar

Classification Summary

VUS14

Likely Benign2

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	12	1	0	14
Likely Benign	0	1	0	1	2
Benign	0	0	0	1	1
Total	1	13	1	2	17

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap EIF4A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →