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EIF2B1
eukaryotic translation initiation factor 2B subunit alpha
The EIF2B1 gene encodes a subunit of eukaryotic translation initiation factor 2B (eIF2B), a protein complex vital for controlling protein production within cells. The EIF2B1 gene provides instructions for the alpha subunit of the eIF2B protein, which plays a key role in regulating how cells produce proteins.
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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Overview
The EIF2B1 gene, full name eukaryotic translation initiation factor 2B subunit alpha, is a critical component in the cellular machinery responsible for protein synthesis. It codes for one of five subunits that together form the eIF2B protein complex. This complex acts as a regulator, ensuring protein production is balanced according to cellular needs and environmental conditions.
What the gene does
The eIF2B protein, which includes the EIF2B1 subunit, is essential for initiating protein synthesis. It interacts with another protein, eIF2, to help start the process of building new proteins. Specifically, eIF2B recycles guanosine triphosphate (GTP) molecules, which provide energy for the initiation factor. This recycling mechanism allows protein synthesis to proceed efficiently.
Under certain cellular conditions, eIF2B can either enhance or slow down protein production. It can increase synthesis by facilitating GTP recycling, or it can reduce synthesis by binding tightly to eIF2, effectively making eIF2B inactive and preventing GTP recycling. This dynamic regulation ensures cells can adapt their protein output, for instance, by synthesising more proteins during growth or fewer during periods of rest.
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Chromosome location
The EIF2B1 gene is located on chromosome 12, specifically at position 12q24.31. This chromosomal location indicates its position on the long arm of chromosome 12.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic changes or variants in the EIF2B1 gene can alter the function of the eIF2B protein. These variants may affect the protein's ability to properly regulate protein synthesis, potentially leading to cellular dysfunction. The specific impact of a variant can depend on its location and type.
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.25_26del | p.Tyr9fs | Pathogenic/Likely pathogenic | ★★☆☆ | Leukoencephalopathy with vanishing white matter 1 |
c.439C>T | p.Arg147Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Leukoencephalopathy with vanishing white matter 1 |
c.458_459del | p.Thr153fs | Pathogenic/Likely pathogenic | ★★☆☆ | EIF2B1-related disorder |
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 |
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 degeneration of the brain's white matter. Impaired eIF2B function, often resulting from these variants, can make it challenging for cells to regulate protein synthesis and cope with stress.
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 national test panels. These include panels for conditions such as "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", "Neurodegenerative disorders, adult onset", and "White matter disorders and cerebral calcification - childhood onset" indicating its clinical relevance in the UK.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the EIF2B1 gene?
The EIF2B1 gene provides instructions for making the alpha subunit of the eIF2B protein. This protein complex is crucial for regulating the initiation of protein synthesis within cells, helping them adapt to changing conditions by controlling protein production.
What conditions are associated with EIF2B1 gene variants?
Variants in the EIF2B1 gene have been linked to leukoencephalopathy with vanishing white matter. This condition involves the progressive deterioration of the brain's white matter, likely due to the impaired ability of cells to regulate protein synthesis under stress.
Is the EIF2B1 gene tested within the NHS in the UK?
Yes, the EIF2B1 gene is part of several NHS England national test panels. These panels cover various neurological conditions, including different forms of ataxia, epilepsy, leukodystrophy, and white matter disorders, reflecting its clinical significance.
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