EIF2B5

Chr 3

eukaryotic translation initiation factor 2B subunit epsilon

Also known as: CACH, CLE, EIF-2B, EIF2Bepsilon, LVWM, VWM5

NCBI Gene: 8893ENSG00000145191UniProt: Q13144

This gene encodes one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. [provided by RefSeq, Nov 2009]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeukoencephalopathy with vanishing white matter 5

Clinical highlights

Gene-disease validity (ClinGen)
leukoencephalopathy with vanishing white matter 5 · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
16
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.44
LOEUF
LOF
Mechanism· G2P
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GeneReview available — EIF2B5
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.44LOEUF
pLI 0.064
Z-score 4.25
OE 0.26 (0.16–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.78Z-score
OE missense 0.89 (0.81–0.97)
346 obs / 389.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.26 (0.16–0.44)
0≤0.351.4
Missense OE?0.89 (0.81–0.97)
0≤0.61.4
Synonymous OE?0.95
0≤1.21.6
LoF obs/exp: 10 / 38.5Missense obs/exp: 346 / 389.1Syn Z: 0.44

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients