EIF4E3

Chr 3

eukaryotic translation initiation factor 4E family member 3

Also known as: eIF-4E3, eIF4E-3

NCBI Gene: 317649 ENSG00000163412 UniProt: Q8N5X7

EIF4E3 encodes a translation initiation factor that recognizes and binds the 7-methylguanosine cap of mRNA during protein synthesis initiation and may inhibit EIF4E1 activity. Mutations cause intellectual developmental disorder with seizures and language delay, inherited in an autosomal recessive pattern. The gene is not highly constrained against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

ResearchSummary from RefSeq, UniProt

EIF4E3 belongs to the EIF4E family of translational initiation factors that interact with the 5-prime cap structure of mRNA and recruit mRNA to the ribosome (Joshi et al., 2004 [PubMed 15153109]).[supplied by OMIM, Mar 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.81

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.018

Z-score 2.05

OE 0.39 (0.20–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.51Z-score

OE missense 0.85 (0.71–1.03)

78 obs / 91.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.20–0.81)

0≤0.351.4

Missense OE?0.85 (0.71–1.03)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 5 / 13.0Missense obs/exp: 78 / 91.8Syn Z: 0.03

Background carrier burden — how many people carry a rare variant somewhere in EIF4E3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 330

335 rare PASS variants

Rare truncating (LoF)

1 in 2,300

60 rare PASS variants

Rare synonymous (reference)

1 in 510

144 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EIF4E3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 390	1 in 2,500
South Asian	~43k	1 in 190	1 in 4,400
Remaining (unassigned)	~30k	1 in 220	1 in 1,900
European (Finnish)	~27k	1 in 1,300	1 in 2,200
Admixed American	~22k	1 in 240	≈ 1 in 5,600
African / African American	~21k	1 in 290	1 in 1,900
East Asian	~20k	1 in 160	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 880	none seen
Middle Eastern	~2,884	1 in 250	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 7 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: 6 of 7 (exon 1 below).? see exons ↓