EIF2B4
Chr 2AReukaryotic translation initiation factor 2B subunit delta
Also known as: EIF-2B, EIF2B, EIF2Bdelta, VWM4
The protein functions as the delta subunit of eukaryotic initiation factor 2B (EIF2B), a GTP exchange factor essential for protein synthesis. Mutations cause leukoencephalopathy with vanishing white matter, sometimes accompanied by ovarian failure, through an autosomal recessive inheritance pattern. The high constraint scores (pLI 0.96, LOEUF 0.33) support that pathogenicity occurs predominantly through loss-of-function mechanisms affecting protein synthesis regulation.
Definitive — sufficient evidence for diagnostic panels
Some data sources returned errors (1)
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
EIF2B4 · 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