EIF4EBP1

Chr 8

eukaryotic translation initiation factor 4E binding protein 1

Also known as: 4E-BP1, 4EBP1, BP-1, PHAS-I

NCBI Gene: 1978 ENSG00000187840 UniProt: Q13541 OMIM: 602223

This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of mRNA translation. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.50

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.50LOEUF

pLI 0.208

Z-score 1.02

OE 0.35 (0.12–1.50)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.82Z-score

OE missense 0.71 (0.56–0.91)

47 obs / 65.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.12–1.50)

0≤0.351.4

Missense OE?0.71 (0.56–0.91)

0≤0.61.4

Synonymous OE?0.78

0≤1.21.6

LoF obs/exp: 1 / 2.9Missense obs/exp: 47 / 65.8Syn Z: 0.86

Background carrier burden — how many people carry a rare variant somewhere in EIF4EBP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 570

147 rare PASS variants

Rare truncating (LoF)

1 in 9,200

25 rare PASS variants

Rare synonymous (reference)

1 in 1,000

66 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EIF4EBP1. 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 720	1 in 9,500
South Asian	~43k	1 in 520	≈ 1 in 19,000
Remaining (unassigned)	~30k	1 in 530	≈ 1 in 14,000
European (Finnish)	~27k	1 in 1,700	≈ 1 in 18,000
Admixed American	~22k	1 in 560	1 in 1,700
African / African American	~21k	1 in 540	1 in 2,500
East Asian	~20k	1 in 400	≈ 1 in 14,000
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	≈ 1 in 580	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): 2 of 3 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: 2 of 3 (exon 3 below).? see exons ↓