EIF2B5
Chr 3AReukaryotic translation initiation factor 2B subunit epsilon
Also known as: CACH, CLE, EIF-2B, EIF2Bepsilon, LVWM, VWM5
The protein is the epsilon subunit of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor that regulates protein synthesis by activating eukaryotic initiation factor 2. Mutations cause leukoencephalopathy with vanishing white matter, an autosomal recessive leukodystrophy that may be associated with ovarian failure in females. The pathogenic mechanism involves loss of function of the EIF2B complex, disrupting cellular protein synthesis regulation.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% 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.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
EIF2B5 · 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
Single Patient Investigational Treatment for Cree Leukoencephalopathy
ACTIVE NOT RECRUITINGResearch Study for Single-Patient Treatment of Cree Leukoencephalopathy/Vanishing White Matter Disease
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools