EIF4A3

Chr 17AR

eukaryotic translation initiation factor 4A3

Also known as: DDX48, Fal1, MUK34, NMP265, NUK34, RCPS, eIF-4A-III, eIF4A-III

This gene encodes an ATP-dependent RNA helicase that functions as a core component of the exon junction complex (EJC), which regulates mRNA splicing, export, localization, translation efficiency, and nonsense-mediated decay. Biallelic loss-of-function mutations cause an autosomal recessive disorder characterized by Robin sequence with cleft mandible and limb anomalies. The pathogenic mechanism involves loss of normal EJC function, which disrupts multiple aspects of mRNA processing and is particularly critical for craniofacial development.

Summary from RefSeq, OMIM, UniProt, Mechanism
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Primary Disease Associations & Inheritance

Robin sequence with cleft mandible and limb anomaliesMIM #268305
AR
UniProtRichieri-Costa-Pereira syndrome
0
Active trials
61
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.12
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryEIF4A3
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 4.64
OE 0.00 (0.000.12)
Highly constrained

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

Missense Constraint
4.02Z-score
OE missense 0.29 (0.240.35)
74 obs / 254.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.12)
00.351.4
Missense OE0.29 (0.240.35)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 0 / 25.0Missense obs/exp: 74 / 254.5Syn Z: -0.81
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEIF4A3-related Richieri-Costa-Pereira syndromeOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4686th %ile
GOF
0.4086th %ile
LOF
0.68top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EIF4A3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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