EIF4H

Chr 7

eukaryotic translation initiation factor 4H

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

This protein stimulates RNA helicase activity during translation initiation and binds mRNA weakly. EIF4H is deleted in Williams syndrome, a multisystem developmental disorder caused by contiguous gene deletion at 7q11.23. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.548), suggesting some intolerance to complete loss of function.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.55
Clinical SummaryEIF4H
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
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ClinVar Variants
166 unique Pathogenic / Likely Pathogenic· 18 VUS of 190 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.440
Z-score 2.74
OE 0.21 (0.100.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.51Z-score
OE missense 0.44 (0.360.54)
69 obs / 157.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.21 (0.100.55)
00.351.4
Missense OE0.44 (0.360.54)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 3 / 14.1Missense obs/exp: 69 / 157.7Syn Z: -0.83
DN
0.5378th %ile
GOF
0.3292th %ile
LOF
0.71top 10%

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

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

190 submitted variants in ClinVar

Classification Summary

Pathogenic160
Likely Pathogenic6
VUS18
Likely Benign3
160
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
160
Likely Pathogenic
6
VUS
18
Likely Benign
3
Benign
0
Total187

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC