EIF2B1

Chr 12AR

eukaryotic translation initiation factor 2B subunit alpha

NCBI Gene: 1967ENSG00000111361UniProt: Q14232

Acts as a component of the translation initiation factor 2B (eIF2B) complex, which catalyzes the exchange of GDP for GTP on eukaryotic initiation factor 2 (eIF2) gamma subunit (PubMed:25858979, PubMed:27023709, PubMed:31048492). Its guanine nucleotide exchange factor activity is repressed when bound to eIF2 complex phosphorylated on the alpha subunit, thereby limiting the amount of methionyl-initiator methionine tRNA available to the ribosome and consequently global translation is repressed (PubMed:25858979, PubMed:31048492)

Primary Disease Associations & Inheritance

Leukoencephalopathy with vanishing white matter 1, with or without ovarian failureMIM #603896
AR
364
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EIF2B1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
364 total variants — no pathogenic classifications of 364 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.98LOEUF
pLI 0.000
Z-score 1.64
OE 0.56 (0.34–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.38Z-score
OE missense 0.70 (0.60–0.81)
114 obs / 163.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.34–0.98)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.60–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 9 / 16.1Missense obs/exp: 114 / 163.7Syn Z: -0.61

ClinVar Variant Classifications

364 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

EIF2B1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Leukoencephalopathy with vanishing white matter 1, with or without ovarian failure

MIM #603896

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Consensus-Based Expert Recommendations for Diagnosis and Clinical Management of Vanishing White Matter.
van Voorst RJ et al.·Neurology
2025Review
Vanishing white matter disease with different faces.
Güngör G et al.·Childs Nerv Syst
2020
The large spectrum of eIF2B-related diseases.
Fogli A et al.·Biochem Soc Trans
2006Review
The spectrum of mutations for the diagnosis of vanishing white matter disease.
Scali O et al.·Neurol Sci
2006Review
Adult-onset leukodystrophy with vanishing white matter: a case series of 19 patients.
Benzoni C et al.·J Neurol
2023Cohort
Identification of ten novel mutations in patients with eIF2B-related disorders.
Ohlenbusch A et al.·Hum Mutat
2005Cohort
Genotypic and phenotypic characteristics of juvenile/adult onset vanishing white matter: a series of 14 Chinese patients.
Ren Y et al.·Neurol Sci
2022Review
Ovarioleukodystrophy due to EIF2B5 mutations.
Ibitoye RT et al.·Pract Neurol
2016Case report
Construction and validation of a prognostic model based on ten signature cell cycle-related genes for early-stage lung squamous cell carcinoma.
Zhang C et al.·Cancer Biomark
2023Functional
[Eukaryotic translation initiation factor 2B and leukoencephalopathy with vanishing white matter].
Pan YX et al.·Beijing Da Xue Xue Bao Yi Xue Ban
2009Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools