EIF4E1B

Chr 5

eukaryotic translation initiation factor 4E family member 1B

NCBI Gene: 253314 ENSG00000175766 UniProt: A6NMX2

The protein recognizes and binds the 7-methylguanosine mRNA cap and facilitates ribosome binding by unwinding mRNA secondary structures during protein synthesis initiation. Mutations in this gene have not yet been definitively associated with human disease. The gene shows tolerance to loss-of-function variants (LOEUF 1.303), suggesting it may not be essential for normal development.

ResearchSummary from RefSeq, UniProt

Predicted to enable RNA 7-methylguanosine cap binding activity and translation initiation factor activity. Predicted to be involved in translational initiation. Predicted to be located in cytoplasm. Predicted to be part of eukaryotic translation initiation factor 4F complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.30

Clinical Summary— EIF4E1B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

34 VUS of 39 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.30LOEUF

pLI 0.000

Z-score 0.74

OE 0.79 (0.49–1.30)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.62Z-score

OE missense 0.85 (0.73–0.99)

115 obs / 135.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.49–1.30)

0≤0.351.4

Missense OE?0.85 (0.73–0.99)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 11 / 14.0Missense obs/exp: 115 / 135.3Syn Z: 0.39

This gene — mechanism propensity

0.6455th %ile

GOF

0.5954th %ile

LOF

0.3357th %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

39 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	34	0	34
Likely Benign	3	1	4
Benign	0	0	0
Total	37	1	38

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

View in ClinVar →

52 pathogenic / likely-pathogenic (of 60) ClinVar copy-number / structural variants overlap EIF4E1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →