EIF4E2

Chr 2

eukaryotic translation initiation factor 4E family member 2

Also known as: 4E-LP, 4EHP, EIF4EL3, IF4e, h4EHP

The EIF4E2 protein recognizes and binds the 7-methylguanosine mRNA cap and acts as a repressor of translation initiation, competing with EIF4E to block assembly of the translation initiation complex. Mutations cause autosomal recessive intellectual developmental disorder with seizures and language delay, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.495), primarily affecting the central nervous system.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
10
Pubs (1 yr)
33
P/LP submissions
0%
P/LP missense
0.49
LOEUF
Mechanism
Clinical SummaryEIF4E2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.58) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 28 VUS of 71 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.582
Z-score 2.96
OE 0.19 (0.090.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.33Z-score
OE missense 0.46 (0.370.56)
66 obs / 144.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.19 (0.090.49)
00.351.4
Missense OE0.46 (0.370.56)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 3 / 15.7Missense obs/exp: 66 / 144.7Syn Z: 0.10

ClinVar Variant Classifications

71 submitted variants in ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic1
VUS28
32
Pathogenic
1
Likely Pathogenic
28
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
1
0
1
VUS
0
23
5
0
28
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total02338061

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

View in ClinVar →

Protein Context — Lollipop Plot

EIF4E2 · 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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