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EIF2B1
eukaryotic translation initiation factor 2B subunit alpha
The EIF2B1 gene provides instructions for a key component of the eIF2B protein, which is essential for regulating protein production within cells and adapting to changing cellular conditions. EIF2B1 encodes the alpha subunit of eukaryotic translation initiation factor 2B (eIF2B).
EIF2B1 is located on the long (q) arm of chromosome 12, at band 12q24.31. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The EIF2B1 gene is responsible for producing one of the five subunits of the eukaryotic translation initiation factor 2B (eIF2B) protein complex, specifically the alpha subunit. This complex is a crucial regulator of protein synthesis, which is the process by which cells create proteins based on genetic instructions. Proper control of protein production is fundamental for cell growth, division, and adaptation to various internal and external stresses.
What the gene does
The EIF2B1 gene provides instructions for the alpha subunit of the eIF2B protein. The eIF2B protein acts as an initiation factor, playing a central role in starting protein synthesis by interacting with another protein, eIF2. This interaction is key to regulating the overall rate of protein production in the cell. Under certain conditions, eIF2B enhances protein synthesis by facilitating the recycling of GTP molecules, which are vital energy carriers for initiation factors. Conversely, eIF2B can slow down protein synthesis by binding tightly to eIF2, rendering it inactive and preventing GTP recycling. This dual regulatory capacity allows cells to precisely manage protein levels, ensuring adequate protein availability for diverse cellular states, such as rapid multiplication versus a resting phase.
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Chromosome location
The EIF2B1 gene is located on chromosome 12, specifically at position 12q24.31. This genomic address specifies its precise placement within the long arm (q) of chromosome 12.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic changes (variants) within the EIF2B1 gene can alter the function of the eIF2B protein. These variants may lead to a partial reduction in the protein's activity, affecting the cell's capacity to regulate protein synthesis effectively and cope with cellular stress.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.439C>T | p.Arg147Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Leukoencephalopathy with vanishing white matter 1 |
c.461_462del | p.Glu154fs | Pathogenic/Likely pathogenic | ★★☆☆ | Leukoencephalopathy with vanishing white matter 1 |
c.588_589del | p.Gly196_Ala197insTer | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
g.(?_124106303)_(124111060_?)del | - | Pathogenic | ★☆☆☆ | not provided |
g.(?_124109314)_(124109429_?)del | - | Pathogenic | ★☆☆☆ | not provided |
g.(?_124114696)_(124118104_?)del | - | Pathogenic | ★☆☆☆ | not provided |
g.(?_124118072)_(124118104_?)del | - | Pathogenic | ★☆☆☆ | not provided |
c.171T>A | p.Cys57Ter | Pathogenic | ★☆☆☆ | not provided |
c.353dup | p.Ile119fs | Pathogenic | ★☆☆☆ | Vanishing white matter disease |
c.552-2A>T | - | Pathogenic | ★☆☆☆ | See cases |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the EIF2B1 gene have been identified in individuals with leukoencephalopathy with vanishing white matter. This condition is characterised by the progressive loss of white matter in the brain, which consists of nerve fibres covered by myelin. Impaired eIF2B function resulting from EIF2B1 variants makes it more challenging for affected cells, particularly in the brain, to regulate protein synthesis and manage changing conditions.
No disease links recorded for this gene in our reference set.
UK clinical status
The EIF2B1 gene is included in several NHS England Genomic Medicine Service clinical panels, indicating its recognised clinical relevance in the UK. These panels cover a range of neurological conditions, including 'Ataxia and cerebellar anomalies - childhood onset', 'Early onset or syndromic epilepsy', 'Hereditary ataxia', 'Hereditary ataxia, adult onset', 'Inherited white matter disorders', 'Leukodystrophy, adult onset', 'Neonatal diabetes', and 'Neurodegenerative disorders, adult onset'. It is also part of the 'White matter disorders and cerebral calcification - childhood onset' panel.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the EIF2B1 gene?
The EIF2B1 gene provides instructions for a subunit of the eIF2B protein, which is crucial for regulating the initiation of protein synthesis within cells. This regulation helps cells adapt to varying conditions and stress.
What health conditions are associated with EIF2B1 variants?
Variants in the EIF2B1 gene are associated with leukoencephalopathy with vanishing white matter. This condition affects the brain's white matter due to the impaired ability of cells to regulate protein production and respond to stress.
How does EIF2B1 affect protein production?
EIF2B1, as part of the eIF2B complex, can both increase and decrease protein synthesis. It does this by recycling or binding to the eIF2 protein, respectively, which controls the availability of energy carriers (GTP) needed to start protein production.
References
- Fogli A, Boespflug-Tanguy O. The large spectrum of eIF2B-related diseases. Biochemical Society transactions. 2006. PMID: 16246171
- Scheper GC, Proud CG, van der Knaap MS. Defective translation initiation causes vanishing of cerebral white matter. Trends in molecular medicine. 2006. PMID: 16545608
- Pronk JC, van Kollenburg B, Scheper GC. Vanishing white matter disease: a review with focus on its genetics. Mental retardation and developmental disabilities research reviews. 2006. PMID: 16807905
- van Kollenburg B, van Dijk J, Garbern J. Glia-specific activation of all pathways of the unfolded protein response in vanishing white matter disease. Journal of neuropathology and experimental neurology. 2006. PMID: 16825957
- Scali O, Di Perri C, Federico A. The spectrum of mutations for the diagnosis of vanishing white matter disease. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2006. PMID: 16998732
- Dietrich J, Lacagnina M, Gass D. EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy. Nature medicine. 2005. PMID: 15723074
- van der Voorn JP, van Kollenburg B, Bertrand G. The unfolded protein response in vanishing white matter disease. Journal of neuropathology and experimental neurology. 2005. PMID: 16141786
- Pavitt GD. eIF2B, a mediator of general and gene-specific translational control. Biochemical Society transactions. 2005. PMID: 16246152
- Fogli A, Schiffmann R, Hugendubler L. Decreased guanine nucleotide exchange factor activity in eIF2B-mutated patients. European journal of human genetics : EJHG. 2004. PMID: 15054402
- Li W, Wang X, Van Der Knaap MS. Mutations linked to leukoencephalopathy with vanishing white matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways. Molecular and cellular biology. 2004. PMID: 15060152