EIF2B2

Chr 14AR

eukaryotic translation initiation factor 2B subunit beta

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

The protein encodes the beta subunit of eukaryotic initiation factor-2B (EIF2B), which regulates protein synthesis by mediating GDP-GTP exchange for activation and deactivation of the translation initiation complex. Biallelic mutations cause leukoencephalopathy with vanishing white matter, an autosomal recessive disorder characterized by progressive white matter degeneration that can be associated with ovarian failure in females. The disease results from loss of EIF2B function, which disrupts cellular protein synthesis regulation particularly under stress conditions.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 1.521 OMIM phenotype
Clinical SummaryEIF2B2
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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.
📋
ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 110 VUS of 367 total submissions
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GeneReview available — EIF2B2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.52LOEUF
pLI 0.000
Z-score 0.04
OE 0.99 (0.661.52)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.03Z-score
OE missense 0.79 (0.690.90)
149 obs / 188.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.99 (0.661.52)
00.351.4
Missense OE0.79 (0.690.90)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 15 / 15.2Missense obs/exp: 149 / 188.8Syn Z: -0.13

ClinVar Variant Classifications

367 submitted variants in ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic26
VUS110
Likely Benign152
Benign23
Conflicting11
30
Pathogenic
26
Likely Pathogenic
110
VUS
152
Likely Benign
23
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
2
13
0
30
Likely Pathogenic
10
12
4
0
26
VUS
0
93
15
2
110
Likely Benign
0
1
63
88
152
Benign
0
2
20
1
23
Conflicting
11
Total2511011591352

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

View in 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.

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