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EIF2B3
eukaryotic translation initiation factor 2B subunit gamma
The EIF2B3 gene provides instructions for producing the gamma subunit of eukaryotic translation initiation factor 2B (eIF2B), a protein crucial for regulating protein synthesis within cells. EIF2B3 plays a vital role in cellular protein production, influencing how cells respond to changing conditions and stress.
EIF2B3 is located on the short (p) arm of chromosome 1, at band 1p34.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The EIF2B3 gene is responsible for encoding a component of the eukaryotic translation initiation factor 2B (eIF2B) protein complex. This complex is fundamental for controlling the rate at which proteins are made in cells, a process known as protein synthesis. Proper regulation of protein synthesis is essential for cellular function and adaptation to various physiological demands.
What the gene does
The EIF2B3 gene specifically provides the blueprint for the gamma subunit of the eIF2B protein. The eIF2B complex acts as a guanine nucleotide exchange factor for another protein, eIF2, which is involved in initiating protein synthesis. Under normal cellular conditions, eIF2B helps to recycle molecules crucial for energy transfer, thereby promoting protein synthesis. However, in response to certain cellular stressors, eIF2B can tightly bind to eIF2, effectively reducing its activity and slowing down protein production. This intricate regulatory mechanism ensures that cells can adjust protein levels to cope with changing environments, such as during periods of rapid cell division or stress. Impaired eIF2B function can hinder a cell's ability to regulate protein synthesis, making it difficult to adapt to diverse conditions.
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Chromosome location
The EIF2B3 gene is situated on the short arm of chromosome 1, at position 1p34.1. This genomic location specifies where the gene resides within the human genome, providing its precise address for genetic mapping and analysis.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the EIF2B3 gene can lead to alterations in the protein's structure or function, potentially impacting its crucial role in regulating protein synthesis. The specific effects of these variants depend on their nature and location within the gene.
Sample of pathogenic variants
7 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.1037T>C | p.Ile346Thr | Pathogenic/Likely pathogenic | ★★☆☆ | Leukoencephalopathy with vanishing white matter 3 |
c.260C>T | p.Ala87Val | Pathogenic/Likely pathogenic | ★★☆☆ | Leukoencephalopathy with vanishing white matter 3 |
c.674G>A | p.Arg225Gln | Pathogenic/Likely pathogenic | ★★☆☆ | Leukoencephalopathy with vanishing white matter 3 |
c.89T>C | p.Val30Ala | Pathogenic/Likely pathogenic | ★★☆☆ | Leukoencephalopathy with vanishing white matter 1 |
c.674G>C | p.Arg225Pro | Pathogenic | ★☆☆☆ | Vanishing white matter disease |
c.1193_1194del | p.Val398fs | Pathogenic | - | Leukoencephalopathy with vanishing white matter 3 |
c.80T>A | p.Leu27Gln | Pathogenic | - | Leukoencephalopathy with vanishing white matter 3 |
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
Genetic variations in the EIF2B3 gene have been identified in a small number of individuals diagnosed with leukoencephalopathy with vanishing white matter [PMID:17968853]. These changes in the gene result in a partial loss of eIF2B protein function. When eIF2B function is compromised, cells struggle to effectively regulate protein synthesis and adapt to changing physiological demands [PMID:17968853].
No disease links recorded for this gene in our reference set.
UK clinical status
The EIF2B3 gene is included in several NHS England Genomic Medicine Service approved panels. These include panels for ataxia and cerebellar anomalies (childhood onset), early onset or syndromic epilepsy, foetal anomalies, hereditary ataxia (both general and adult onset), inherited white matter disorders, leukodystrophy (adult onset), neurodegenerative disorders (adult onset), and white matter disorders and cerebral calcification (childhood onset). Its presence on these panels indicates its clinical relevance in the UK healthcare system.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the EIF2B3 gene do?
The EIF2B3 gene provides instructions for making the gamma subunit of the eIF2B protein, which is vital for controlling protein production in cells. It helps cells manage how much protein they make, adapting to different cellular needs and stress.
What happens if the EIF2B3 gene doesn't work correctly?
If the EIF2B3 gene is not functioning properly, it can impair a cell's ability to regulate protein synthesis effectively. This can lead to difficulties in cellular adaptation to changing conditions and is associated with conditions affecting the brain's white matter, such as leukoencephalopathy with vanishing white matter [PMID:17968853].
Is the EIF2B3 gene relevant to UK clinical practice?
Yes, the EIF2B3 gene is part of several NHS England approved panels for genetic testing. These panels cover various neurological and developmental conditions, highlighting its clinical significance in the UK.
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