EIF2B1
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">EIF2B1</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>EIF2B1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>EIF2B1</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=EIF2B1" target="_blank">Search NCBI</a></td>
</tr>
</table>
{
"path": "genes/eif2b1",
"title": "EIF2B1",
"content": "# EIF2B1
<div class=\"infobox infobox-gene\"> [@mutations2012]
<table> [@integrated2020]
<tr><th>Gene Symbol</th><td>EIF2B1</td></tr>
<tr><th>Full Name</th><td>Eukaryotic Translation Initiation Factor 2B Subunit Alpha</td></tr>
<tr><th>Chromosomal Location</th><td>12q24.31</td></tr>
<tr><th>NCBI Gene ID</th><td><a href=\"https://www.ncbi.nlm.nih.gov/gene/19688\" target=\"_blank\">19688</a></td></tr>
<tr><th>OMIM</th><td><a href=\"https://www.omim.org/entry/606686\" target=\"_blank\">606686</a></td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000111361</td></tr>
<tr><th>UniProt ID</th><td><a href=\"https://www.uniprot.org/uniprot/P49411\" target=\"_blank\">P49411</a></td></tr>
<tr><th>Associated Diseases</th><td><a href=\"/diseases/vanishing-white-matter-disease\">Vanishing White Matter Disease</a>, <a href=\"/diseases/leukoencephalopathy\">Leukoencephalopathy</a></td></tr>
</table>
</div>
Overview
EIF2B1 (Eukaryotic Translation Initiation Factor 2B Subunit Alpha) encodes the alpha subunit of eIF2B, the guanine nucleotide exchange factor (GEF) essential for eukaryotic translation initiation. Located at chromosome 12q24.31, this gene is ubiquitously expressed with highest levels in brain white matter and is critical for cellular stress responses. EIF2B1 mutations cause vanishing white matter disease (VWM), an autosomal recessive leukoencephalopathy, making it a key target for understanding integrated stress response mechanisms in neurodegeneration.
Introduction
EIF2B1 (Eukaryotic Translation Initiation Factor 2B Subunit Alpha) is a critical gene encoding the alpha subunit of eIF2B, the guanine nucleotide exchange factor that recycles eIF2-GDP to eIF2-GTP. This process is essential for translational initiation in all eukaryotic cells. The gene is located on chromosome 12q24.31 and is ubiquitously expressed with high levels in brain white matter.
Background
The eIF2B complex consists of five subunits (alpha, beta, gamma, delta, epsilon) and functions as a critical regulator of translational control. EIF2B1 mutations cause vanishing white matter disease (VWM), an autosomal recessive leukoencephalopathy characterized by progressive neurological deterioration. Understanding EIF2B1 function is crucial for developing therapies targeting the integrated stress response in neurodegenerative diseases.
EIF2B1 (Eukaryotic Translation Initiation Factor 2B Subunit Alpha) is a critical gene encoding the alpha subunit of eIF2B, the guanine nucleotide exchange factor that recycles eIF2-GDP to eIF2-GTP. This process is essential for translational initiation in all eukaryotic cells.
EIF2B1 mutations cause vanishing white matter disease (VWM), a autosomal recessive leukoencephalopathy characterized by progressive neurological deterioration. The gene is located on chromosome 12q24.31 and is ubiquitously expressed with high levels in brain white matter.
Function
EIF2B1 encodes the alpha subunit of eukaryotic translation initiation factor 2B (eIF2B), which is the guanine nucleotide exchange factor (GEF) for eIF2. eIF2B is essential for protein synthesis initiation as it recycles eIF2-GDP to eIF2-GTP, allowing the formation of the ternary complex that delivers the initiator methionine tRNA to the ribosome<sup><a href=\"#references\">[1]</a></sup>.
The eIF2B complex consists of five subunits (alpha, beta, gamma, delta, epsilon) and functions as a critical regulator of translational control. Under cellular stress conditions such as endoplasmic reticulum (ER) stress, eIF2B activity is downregulated through phosphorylation of its substrate eIF2, leading to global translational repression while selectively promoting the translation of stress-response genes<sup><a href=\"#references\">[2]</a></sup>.
Disease Associations
Vanishing White Matter Disease (VWM)
Mutations in EIF2B1 are associated with vanishing white matter disease (VWM), also known as childhood ataxia with central hypomyelinization (CACH). This is an autosomal recessive neurological disorder characterized by progressive cerebellar ataxia, spasticity, and motor deterioration. The disease typically presents in early childhood and leads to progressive white matter loss in the brain<sup><a href=\"#references\">[3]</a></sup>.
The pathophysiology involves defective eIF2B function leading to impaired stress response in oligodendrocytes and [astrocytes](/entities/astrocytes). Patients with EIF2B1 mutations show reduced eIF2B activity, compromising the integrated stress response (ISR) that normally protects cells from various forms of cellular stress<sup><a href=\"#references\">[4]</a></sup>.
Leukoencephalopathy
EIF2B1 mutations can also cause a broader spectrum of leukoencephalopathies, including milder adult-onset forms. These conditions involve abnormal white matter in the brain, visible on MRI as diffuse signal changes<sup><a href=\"#references\">[5]</a></sup>.
Expression
EIF2B1 is ubiquitously expressed in all tissues, with high expression in the brain, particularly in oligodendrocytes, astrocytes, and [neurons](/entities/neurons). The protein is localized in the cytoplasm where it participates in the translation initiation complex formation. In the brain, eIF2B is especially critical in white matter tracts due to the high metabolic demands of myelinating glia<sup><a href=\"#references\">[6]</a></sup>.
Cross-References
- eIF2B1 Protein
- Vanishing White Matter Disease
- [ER Stress Pathway](/mechanisms/er-stress) Integrated Stress Response
See Also
- [Genes Index](/genes)
- Eukaryotic Translation Initiation
- [Protein Synthesis](/mechanisms/protein-synthesis)
- Translation Control
External Links
- [Allen Brain Cell Atlas](https://portal.brain-map.org/atlases-and-data/rnaseq) - Cell type expression data
- [Human Cell Atlas](https://www.humancellatlas.org/) - Single-cell transcriptomics
- [NeuroMorpho.Org](https://neuromorpho.org/) - Neuronal morphology database
References
[Unknown, Molecular cloning of the murine and human eukaryotic translation initiation factor EIF2B (1989) (1989)](https://doi.org/10.1016/0014-5793(89)
[Unknown, The structural basis of eIF2B function and regulation (2018) (2018)](https://doi.org/10.1016/j.tibs.2018.04.004)
[Unknown, Vanishing white matter disease: a clinicopathological entity (2002) (2002)](https://pubmed.ncbi.nlm.nih.gov/11912497/)
[Unknown, eIF2B and disease: from mechanism to therapy (2019) (2019)](https://doi.org/10.1016/j.neuropharm.2019.107745)
[Unknown, Mutations in EIF2B1: expanding the phenotype of vanishing white matter disease (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22578432/)
[Unknown, Integrated stress response in oligodendrocyte survival and myelination (2020) (2020)](https://doi.org/10.1002/glia.23899)