EIF3E

Chr 8

eukaryotic translation initiation factor 3 subunit E

Also known as: EIF3-P48, EIF3S6, INT6, eIF3-p46

The EIF3E protein is a component of the eukaryotic translation initiation factor 3 complex, which is essential for protein synthesis by facilitating ribosome assembly and mRNA recruitment during translational initiation. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.533), affecting primarily the central nervous system and growth parameters.

Summary from RefSeq, UniProt
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0
Active trials
6
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.53
LOEUF
DN
Mechanism· predicted
Clinical SummaryEIF3E
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.53LOEUF
pLI 0.052
Z-score 3.29
OE 0.28 (0.160.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.13Z-score
OE missense 0.42 (0.360.50)
97 obs / 230.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.28 (0.160.53)
00.351.4
Missense OE0.42 (0.360.50)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 7 / 24.7Missense obs/exp: 97 / 230.7Syn Z: -0.74
DN
0.6939th %ile
GOF
0.5857th %ile
LOF
0.3261th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EIF3E · 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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