EIF2B1

Chr 12AR

eukaryotic translation initiation factor 2B subunit alpha

Also known as: EIF2B, EIF2BA, EIF2Balpha, VWM1

The protein is a subunit of eukaryotic translation initiation factor 2B, which functions as a GTP exchange factor for eukaryotic initiation factor 2 and regulates protein synthesis. Mutations cause leukoencephalopathy with vanishing white matter, inherited in an autosomal recessive pattern, with some patients also developing ovarian failure. Disease mutations can cause pathogenicity through dominant-negative effects that disrupt the essential regulatory function of the EIF2B complex.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.981 OMIM phenotype
Clinical SummaryEIF2B1
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Gene-Disease Validity (ClinGen)
leukoencephalopathy with vanishing white matter 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.64
OE 0.56 (0.340.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.38Z-score
OE missense 0.70 (0.600.81)
114 obs / 163.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.340.98)
00.351.4
Missense OE0.70 (0.600.81)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 9 / 16.1Missense obs/exp: 114 / 163.7Syn Z: -0.61
DN
0.7035th %ile
GOF
0.4579th %ile
LOF
0.3162th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EIF2B1 · 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
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