EIF2B1 Gene
Eukaryotic Translation Initiation Factor 2B Subunit Alpha
Gene Information Card
| Symbol | EIF2B1 |
|---|---|
| Full Name | Eukaryotic Translation Initiation Factor 2B Subunit Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 1967 ncbi.nlm.nih.gov/gene/1967 |
| Ensembl ID | ENSG00000111371 |
| UniProt ID | Q14232 |
| OMIM ID | 606686 |
| HGNC ID | 3258 |
| Aliases | EIF2B, eIF-2B alpha subunit, EIF2Balpha |
Description
EIF2B1 encodes the alpha subunit of eukaryotic translation initiation factor 2B (eIF2B), a guanine nucleotide exchange factor essential for protein synthesis. eIF2B catalyzes the exchange of GDP for GTP on eIF2, a key step in translation initiation. Mutations in EIF2B1 cause leukoencephalopathy with vanishing white matter (VWM), also known as childhood ataxia with central nervous system hypomyelination (CACH).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Leukoencephalopathy with vanishing white matter (VWM) | Impaired eIF2B guanine nucleotide exchange activity leads to defective translation initiation under stress conditions, causing selective vulnerability of oligodendrocytes and astrocytes. | OMIM #603896; ClinVar pathogenic variants |
| Childhood ataxia with central nervous system hypomyelination (CACH) | Same mechanism as VWM; reduced eIF2B activity disrupts myelin maintenance and repair. | OMIM #603896; multiple case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Liver | 8.7 | Medium |
| Kidney | 7.5 | Medium |
| Heart | 6.9 | Low |
| Lung | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| HeLa | 11.8 | Medium expression |
| K562 | 9.1 | Medium expression |
| SH-SY5Y | 13.5 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.259C>T (p.Arg87Trp) | Missense | Rare | Reduced eIF2B complex stability and GEF activity |
| c.338G>A (p.Arg113His) | Missense | Rare | Impaired eIF2B catalytic function |
| c.583C>T (p.Arg195Cys) | Missense | Rare | Dominant-negative effect on eIF2B complex |
Mutation functional classification
Loss of Function (LOF)
Most missense mutations reduce eIF2B GEF activity, leading to impaired translation initiation.
Gain of Function (GOF)
Not reported for EIF2B1.
Dominant Negative (DN)
Some mutations (e.g., p.Arg195Cys) exert dominant-negative effects by disrupting the eIF2B holocomplex.
View complete mutation data：
Gene Ontology (GO)
Pathways
• hsa03013 - RNA transport (eIF2B-mediated)
• hsa04141 - Protein processing in endoplasmic reticulum (eIF2B stress response)
• REACT:16888 - Translation initiation complex formation
Protein Summary
EIF2B1 encodes the alpha subunit of the eIF2B complex, a heterodecameric guanine nucleotide exchange factor (GEF) that recycles eIF2 from its inactive GDP-bound form to the active GTP-bound form. The alpha subunit is regulatory and stabilizes the complex. Reduced eIF2B activity due to mutations leads to chronic translational stress, particularly affecting glial cells, resulting in progressive leukoencephalopathy.
Related Services
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