EIF3F

Chr 11AR

eukaryotic translation initiation factor 3 subunit F

Also known as: EIF3S5, MRT67, eIF3-p47

NCBI Gene: 8665ENSG00000175390UniProt: O00303

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]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 67MIM #618295
AR
106
ClinVar variants
20
Pathogenic / LP
0.97
pLI score· haploinsufficient
1
Active trials
Clinical Summary— EIF3F
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Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 57 VUS of 106 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.11Z-score
OE missense 1.02 (0.91–1.14)
212 obs / 207.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.02–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.91–1.14)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.31
0≤1.21.6
LoF obs/exp: 1 / 15.3Missense obs/exp: 212 / 207.6Syn Z: -2.24

ClinVar Variant Classifications

106 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic3
VUS57
Likely Benign21
Benign8
17
Pathogenic
3
Likely Pathogenic
57
VUS
21
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
16
0
17
Likely Pathogenic
0
2
1
0
3
VUS
1
48
7
1
57
Likely Benign
0
4
1
16
21
Benign
0
4
2
2
8
Total2582719106

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

View in ClinVar →

Protein Context — Lollipop Plot

EIF3F · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

EIF3F-related developmental disorder

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal recessive 67

MIM #618295

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
eIF3f promotes tumour malignancy by remodelling fatty acid biosynthesis in hepatocellular carcinoma.
Zhou S et al.·J Hepatol
2025Functional
EIF3F-related neurodevelopmental disorder: refining the phenotypic and expanding the molecular spectrum.
Hüffmeier U et al.·Orphanet J Rare Dis
2021
Male specific conserved LncRNA TSCL1 regulated target mRNA translation by interaction with PIWIL1.
Lu S et al.·Cell Death Differ
2026
Muscle wasting in cancer.
Johns N et al.·Int J Biochem Cell Biol
2013Review
Clinicopathologic Implications of Eukaryotic Initiation Factor 3f and Her-2/neu Expression in Gastric Cancer.
Cheng Y et al.·Clin Transl Sci
2015
Exploration of Diagnostic Deubiquitinating Enzymes in Endometriosis and Its Immune Infiltration.
Yang X et al.·Biochem Genet
2024
Analysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair loss.
Henne SK et al.·Nat Commun
2023
Identification of recurrent pathogenic alleles using exome sequencing data: Proof-of-concept study of Russian subjects.
Orlov IE et al.·Eur J Med Genet
2022
The translation initiation complex eIF3 in trypanosomatids and other pathogenic excavates--identification of conserved and divergent features based on orthologue analysis.
Rezende AM et al.·BMC Genomics
2014
Obesity significantly alters the human sperm proteome, with potential implications for fertility.
Pini T et al.·J Assist Reprod Genet
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools