EIF2B2

Chr 14AR

eukaryotic translation initiation factor 2B subunit beta

Also known as: EIF-2Bbeta, EIF2B, EIF2Bbeta, VWM2

NCBI Gene: 8892ENSG00000119718UniProt: P49770

This gene encodes the beta subunit of eukaryotic initiation factor-2B (EIF2B). EIF2B is involved in protein synthesis and exchanges GDP and GTP for its activation and deactivation. [provided by RefSeq, Aug 2011]

Primary Disease Associations & Inheritance

Leukoencephalopathy with vanishing white matter 2, with or without ovarian failureMIM #620312
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EIF2B2
🧬
Gene-Disease Validity (ClinGen)
leukoencephalopathy with vanishing white matter 2 · 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

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.
1.52LOEUF
pLI 0.000
Z-score 0.04
OE 0.99 (0.66–1.52)
Tolerant

Highly tolerant — LoF variants common in population

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.
1.03Z-score
OE missense 0.79 (0.69–0.90)
149 obs / 188.8 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.0.99 (0.66–1.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.69–0.90)
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.1.02
0≤1.21.6
LoF obs/exp: 15 / 15.2Missense obs/exp: 149 / 188.8Syn Z: -0.13

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

EIF2B2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

EIF2B2-related leukoencephalopathy with vanishing white matter

strong
ARUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Leukoencephalopathy with vanishing white matter 2, with or without ovarian failure

MIM #620312

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — EIF2B2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The genetic and phenotypic spectra of adult genetic leukoencephalopathies in a cohort of 309 patients.
Wu C et al.·Brain
2023Cohort
Screening of premature ovarian insufficiency associated genes in Hungarian patients with next generation sequencing.
Illés A et al.·BMC Med Genomics
2024Cohort
Vanishing white matter disease: an Italian case with A638G mutation in exon 5 of EIF2B2 gene, an unusual early onset and a long course.
Sambati L et al.·Neurol Sci
2013Review
The impact of immunity on the risk of coronary artery disease: insights from a multiomics study.
Bian R et al.·Postgrad Med J
2024
Analysis of copy number variation in men with non-obstructive azoospermia.
Wyrwoll MJ et al.·Andrology
2022
The spectrum of mutations for the diagnosis of vanishing white matter disease.
Scali O et al.·Neurol Sci
2006Review
Identification of novel genetic causes of Rett syndrome-like phenotypes.
Lopes F et al.·J Med Genet
2016
Type 2 Diabetes Modifies the Association of CAD Genomic Risk Variants With Subclinical Atherosclerosis.
Hasbani NR et al.·Circ Genom Precis Med
2023
Adult-onset vanishing white matter disease with the EIF2B2 gene mutation presenting as menometrorrhagia.
Wei C et al.·BMC Neurol
2019Case report
EIF2B2 gene mutation causing early onset vanishing white matter disease: a case report.
Filareto I et al.·Ital J Pediatr
2022Case report
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.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools