EIF4H

Chr 7

eukaryotic translation initiation factor 4H

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

NCBI Gene: 7458 ENSG00000106682 UniProt: Q15056 OMIM: 603431

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.55

Clinical Summary— EIF4H

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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

13 VUS of 18 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.21 (0.10–0.55)

0≤0.351.4

Missense OE?0.44 (0.36–0.54)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 3 / 14.1Missense obs/exp: 69 / 157.7Syn Z: -0.83

This gene — mechanism propensity

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

18 submitted variants in ClinVar

ClinVar

Classification Summary

VUS13

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	13	0	13
Likely Benign	1	1	2
Benign	0	0	0
Total	14	1	15

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

View in ClinVar →

167 pathogenic / likely-pathogenic (of 173) ClinVar copy-number / structural variants overlap EIF4H — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →