EIF2B3

Chr 1AR

eukaryotic translation initiation factor 2B subunit gamma

Also known as: EIF-2B, EIF2Bgamma, VWM3

The protein encoded by this gene is a subunit of eukaryotic initiation factor 2B (eIF2B), which catalyzes the exchange of GDP for GTP on eIF2 and is essential for protein synthesis regulation. Mutations cause leukoencephalopathy with vanishing white matter (also known as childhood ataxia with central nervous system hypomyelination), an autosomal recessive leukodystrophy characterized by progressive white matter deterioration that can be triggered by stress, fever, or minor trauma. The disease results from loss of eIF2B function, leading to impaired cellular stress responses and white matter degeneration.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.431 OMIM phenotype
Clinical SummaryEIF2B3
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Gene-Disease Validity (ClinGen)
leukoencephalopathy with vanishing white matter 3 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.57) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 34 VUS of 200 total submissions
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GeneReview available — EIF2B3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.43LOEUF
pLI 0.567
Z-score 3.63
OE 0.21 (0.110.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.04Z-score
OE missense 0.81 (0.720.91)
198 obs / 243.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.110.43)
00.351.4
Missense OE0.81 (0.720.91)
00.61.4
Synonymous OE0.80
01.21.6
LoF obs/exp: 5 / 24.3Missense obs/exp: 198 / 243.9Syn Z: 1.41

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic6
VUS34
Likely Benign141
Benign6
Conflicting1
1
Pathogenic
6
Likely Pathogenic
34
VUS
141
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
2
3
1
0
6
VUS
0
32
2
0
34
Likely Benign
1
2
61
77
141
Benign
0
0
6
0
6
Conflicting
1
Total3377177189

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

View in ClinVar →

Protein Context — Lollipop Plot

EIF2B3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC