EIF3H
Chr 8eukaryotic translation initiation factor 3 subunit H
Also known as: EIF3S3, eIF3-gamma, eIF3-p40
The EIF3H protein is a component of the eukaryotic translation initiation factor 3 complex, which is essential for initiating protein synthesis by facilitating ribosome assembly and mRNA recruitment. Mutations in this gene cause autosomal recessive intellectual developmental disorder with seizures, hypotonia, and brain abnormalities, with onset in infancy or early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.59), and the disorder primarily affects the central nervous system with developmental delays and neurological manifestations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
134 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 54 | 0 | 54 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 43 | 14 | 0 | 57 |
Likely Benign | 0 | 0 | 1 | 0 | 1 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 43 | 69 | 0 | 112 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
EIF3H · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools