EIF3E

Chr 8

eukaryotic translation initiation factor 3 subunit E

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

NCBI Gene: 3646 ENSG00000104408 UniProt: P60228 OMIM: 602210

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity and cadherin binding activity. Contributes to translation initiation factor activity. Involved in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; positive regulation of translation; and translational initiation. Located in PML body and cytosol. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.53

Clinical Summary— EIF3E

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

13 VUS of 48 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.53LOEUF

pLI 0.052

Z-score 3.29

OE 0.28 (0.16–0.53)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.13Z-score

OE missense 0.42 (0.36–0.50)

97 obs / 230.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.28 (0.16–0.53)

0≤0.351.4

Missense OE?0.42 (0.36–0.50)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 7 / 24.7Missense obs/exp: 97 / 230.7Syn Z: -0.74

This gene — mechanism propensity

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

48 submitted variants in ClinVar

ClinVar

Classification Summary

VUS13

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	13	13
Likely Benign	0	0
Benign	0	0
Total	13	13

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap EIF3E — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →