EIF3B

Chr 7

eukaryotic translation initiation factor 3 subunit B

Also known as: EIF3-ETA, EIF3-P110, EIF3-P116, EIF3S9, PRT1

NCBI Gene: 8662 ENSG00000106263 UniProt: P55884 OMIM: 603917

EIF3B encodes an RNA-binding component of the eukaryotic translation initiation factor 3 complex, which is essential for protein synthesis initiation, mRNA recruitment to ribosomes, and ribosomal subunit assembly. Mutations cause autosomal dominant developmental delay with variable intellectual disability and dysmorphic features, with onset in early childhood. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in several processes, including IRES-dependent viral translational initiation; translational initiation; and viral translational termination-reinitiation. Located in cytoplasmic stress granule. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.07

Clinical Summary— EIF3B

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

140 VUS of 218 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.07LOEUF

pLI 1.000

Z-score 6.19

OE 0.00 (0.00–0.07)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

1.82Z-score

OE missense 0.75 (0.69–0.83)

327 obs / 433.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.07)

0≤0.351.4

Missense OE?0.75 (0.69–0.83)

0≤0.61.4

Synonymous OE?1.39

0≤1.21.6

LoF obs/exp: 0 / 44.6Missense obs/exp: 327 / 433.7Syn Z: -3.97

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateEIF3B-related neurodevelopmental disorder with cardiac anomalies and craniofacial dysmorphismLOFAD

This gene — mechanism propensity

0.2997th %ile

GOF

0.2994th %ile

LOF

0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.07

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

218 submitted variants in ClinVar

ClinVar

Classification Summary

VUS140

Likely Benign4

Benign31

140

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	9	130	1	0	140
Likely Benign	0	1	0	3	4
Benign	0	2	22	7	31
Total	9	133	23	10	175

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

View in ClinVar →

36 pathogenic / likely-pathogenic (of 61) ClinVar copy-number / structural variants overlap EIF3B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →