EIF4H

Chr 7

eukaryotic translation initiation factor 4H

Also known as: WBSCR1, WSCR1, eIF-4H

NCBI Gene: 7458ENSG00000106682UniProt: Q15056

This gene encodes one of the translation initiation factors, which functions to stimulate the initiation of protein synthesis at the level of mRNA utilization. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

185
ClinVar variants
164
Pathogenic / LP
0.44
pLI score
0
Active trials
Clinical Summary— EIF4H
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
📋
ClinVar Variants
164 Pathogenic / Likely Pathogenic· 18 VUS of 185 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.55LOEUF
pLI 0.440
Z-score 2.74
OE 0.21 (0.10–0.55)
Moderately constrained

More LoF-intolerant than ~75% 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.
2.51Z-score
OE missense 0.44 (0.36–0.54)
69 obs / 157.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.21 (0.10–0.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.44 (0.36–0.54)
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.1.14
0≤1.21.6
LoF obs/exp: 3 / 14.1Missense obs/exp: 69 / 157.7Syn Z: -0.83

ClinVar Variant Classifications

185 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic158
Likely Pathogenic6
VUS18
Likely Benign3
158
Pathogenic
6
Likely Pathogenic
18
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————158
Likely Pathogenic
————6
VUS
————18
Likely Benign
————3
Benign
————0
Total—185

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EIF4H · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Cytoskeletal protein KRT14 governs cisplatin resistance by modulating eIF4H-dependent ACOX2 translation and lipid metabolism in bladder cancer.
Liu S et al.·Cell Death Dis
2025
Refining housekeeping genes and demonstrating their potential for clinical and experimental applications.
Hwang KW et al.·Comput Biol Med
2025
RNA binding motif protein 10 suppresses lung cancer progression by controlling alternative splicing of eukaryotic translation initiation factor 4H.
Zhang S et al.·EBioMedicine
2020
An alternative splicing isoform of eukaryotic initiation factor 4H promotes tumorigenesis in vivo and is a potential therapeutic target for human cancer.
Wu D et al.·Int J Cancer
2011
Risk model based on genes regulating the response of tumor cells to T-cell-mediated killing in esophageal squamous cell carcinoma.
Zhang X et al.·Aging (Albany NY)
2024Functional
SpliceVista, a tool for splice variant identification and visualization in shotgun proteomics data.
Zhu Y et al.·Mol Cell Proteomics
2014
High-throughput screening identifies histone deacetylase inhibitors that modulate GTF2I expression in 7q11.23 microduplication autism spectrum disorder patient-derived cortical neurons.
Cavallo F et al.·Mol Autism
2020
A Novel Recurrent Breakpoint Responsible for Rearrangements in the Williams-Beuren Region.
Plaja A et al.·Cytogenet Genome Res
2015Case report
Fullerenes May Cause eIF Mediated Perturbation in Translational Machinery: Evidence from in-silico Analysis.
Firdaus S et al.·Ann Clin Lab Sci
2017
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools