EIF3F

Chr 11AR

eukaryotic translation initiation factor 3 subunit F

Also known as: EIF3S5, MRT67, eIF3-p47

NCBI Gene: 8665 ENSG00000175390 UniProt: O00303 OMIM: 603914

The EIF3F protein is a component of the eukaryotic translation initiation factor 3 complex, which is required for protein synthesis initiation by facilitating ribosome assembly and mRNA recruitment. Mutations cause autosomal recessive intellectual developmental disorder 67. This gene is highly constrained against loss-of-function mutations in the general population, indicating that such variants are likely to be pathogenic when present in the homozygous or compound heterozygous state.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables identical protein binding activity and metal-dependent deubiquitinase activity. Contributes to translation initiation factor activity. Involved in IRES-dependent viral translational initiation and translational initiation. Located in membrane. Part of eukaryotic translation initiation factor 3 complex. Implicated in autosomal recessive intellectual developmental disorder 67. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 67MIM #618295

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · syndromic intellectual disability · AR · ClinGen 2023

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.31

LOEUF· LoF intol.

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.970

Z-score 3.39

OE 0.07 (0.02–0.31)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

-0.11Z-score

OE missense 1.02 (0.91–1.14)

212 obs / 207.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.07 (0.02–0.31)

0≤0.351.4

Missense OE?1.02 (0.91–1.14)

0≤0.61.4

Synonymous OE?1.31

0≤1.21.6

LoF obs/exp: 1 / 15.3Missense obs/exp: 212 / 207.6Syn Z: -2.24

Background carrier burden — how many people carry a rare variant somewhere in EIF3F?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

512 rare PASS variants

Rare truncating (LoF)

1 in 12,000

21 rare PASS variants

Rare synonymous (reference)

1 in 160

221 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EIF3F. 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 210	1 in 12,000
South Asian	~43k	1 in 100	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 98	≈ 1 in 15,000
European (Finnish)	~27k	1 in 450	≈ 1 in 8,900
Admixed American	~22k	1 in 100	none seen
African / African American	~21k	1 in 59	≈ 1 in 7,500
East Asian	~20k	1 in 120	≈ 1 in 6,400
Ashkenazi Jewish	~13k	1 in 810	none seen
Middle Eastern	~2,884	1 in 130	≈ 1 in 2,900

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): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓