EIF4A2

Chr 3ADAR

eukaryotic translation initiation factor 4A2

Also known as: BM-010, DDX2B, EIF4A, EIF4F, NEDHSS, eIF-4A-II, eIF4A-II

NCBI Gene: 1974ENSG00000156976UniProt: Q14240

Enables ATP hydrolysis activity. Involved in negative regulation of RNA-dependent RNA polymerase activity. Located in perinuclear region of cytoplasm. Implicated in neurodevelopmental disorder with hypotonia and speech delay. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia and speech delay, with or without seizuresMIM #620455
ADAR
140
ClinVar variants
62
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— EIF4A2
⚡
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
62 Pathogenic / Likely Pathogenic· 65 VUS of 140 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.
0.20LOEUF
pLI 0.998
Z-score 4.26
OE 0.04 (0.01–0.20)
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.
3.89Z-score
OE missense 0.27 (0.22–0.33)
60 obs / 224.1 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.0.04 (0.01–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.27 (0.22–0.33)
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.1.36
0≤1.21.6
LoF obs/exp: 1 / 23.1Missense obs/exp: 60 / 224.1Syn Z: -2.41

ClinVar Variant Classifications

140 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic17
VUS65
Likely Benign9
Benign3
Conflicting1
45
Pathogenic
17
Likely Pathogenic
65
VUS
9
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
3
41
0
45
Likely Pathogenic
4
8
5
0
17
VUS
15
38
11
1
65
Likely Benign
0
0
4
5
9
Benign
0
0
2
1
3
Conflicting
—1
Total2049637140

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

View in ClinVar →

Protein Context — Lollipop Plot

EIF4A2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

EIF4A2-related neurodevelopmental disorder

limited
ARUndeterminedDecreased Gene Product Level
Dev. Disorders
G2P ↗
inframe deletionframeshift variant NMD triggering

EIF4A2-related neurodevelopmental disorder with hypotonia and epilepsy

moderate
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantframeshift variant NMD triggering

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures

MIM #620455

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
📖
GeneReview available — EIF4A2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Rare EIF4A2 variants are associated with a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy.
Paul MS et al.·Am J Hum Genet
2023
Downregulation of EIF4A2 in non-small-cell lung cancer associates with poor prognosis.
Shaoyan X et al.·Clin Lung Cancer
2013
Identification of tumor antigens and immune landscapes for bladder urothelial carcinoma mRNA vaccine.
Sun Z et al.·Front Immunol
2023
Two Novel Pediatric Cases of EIF4A2 -Related Disorder With Refractory Infantile Spasms.
Painter J et al.·Am J Med Genet A
2026Case report
β-glucuronidase use as a single internal control gene may confound analysis in FMR1 mRNA toxicity studies.
Kraan CM et al.·PLoS One
2018
MicroRNA-5195-3p enhances the chemosensitivity of triple-negative breast cancer to paclitaxel by downregulating EIF4A2.
Liu M et al.·Cell Mol Biol Lett
2019
Translational dysregulation in cancer: eIF4A isoforms and sequence determinants of eIF4A dependence.
Raza F et al.·Biochem Soc Trans
2015Review
Identification of novel MECOM gene fusion and personalized therapeutic targets through integrative clinical sequencing in secondary acute myeloid leukemia in a patient with severe congenital neutropenia: a case report and literature review.
Connelly JA et al.·Cold Spring Harb Mol Case Stud
2018Review
Novel loci for triglyceride/HDL-C ratio longitudinal change among subjects without T2D.
Wang L et al.·J Lipid Res
2025Natural history
Shear Stress Markedly Alters the Proteomic Response to Hypoxia in Human Pulmonary Endothelial Cells.
Kostyunina DS et al.·Am J Respir Cell Mol Biol
2023
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