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…

LOFmechanismARLOEUF 0.311 OMIM phenotype

Clinical Summary— EIF3F

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Gene-Disease Validity (ClinGen)

syndromic intellectual disability · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 52 VUS of 96 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongEIF3F-related developmental disorderLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.4488th %ile

GOF

0.4875th %ile

LOF

0.65top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

96 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic3

VUS52

Likely Benign21

Benign8

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	1	2	0	0	3
VUS	1	48	2	1	52
Likely Benign	0	4	1	16	21
Benign	0	4	2	2	8
Total	3	58	5	19	85

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap EIF3F — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →