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EIF2B3

eukaryotic translation initiation factor 2B subunit gamma

The EIF2B3 gene provides instructions for making a critical subunit of the eIF2B protein, which plays a central role in controlling protein production within cells. EIF2B3 is responsible for producing the gamma subunit of eukaryotic translation initiation factor 2B (eIF2B).

Chromosome 1p34.1 Various HGNC:3259 Tier C
EIF2B3 1p34.1 p arm q arm 1

EIF2B3 is located on the short (p) arm of chromosome 1, at band 1p34.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 1 in the library →

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Clinical tests that include this

Carrier Screening panel
EIF2B3 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The EIF2B3 gene encodes a component of the eukaryotic translation initiation factor 2B (eIF2B) protein complex. This complex is essential for managing the overall rate of protein synthesis in human cells, influencing how cells respond to stress and changing metabolic demands.

Disruptions in the function of the eIF2B complex, often due to variants in genes like EIF2B3, can have significant health implications, particularly affecting the brain's white matter.

What the gene does

The EIF2B3 gene instructs the cell to produce the gamma subunit of the eIF2B protein. The eIF2B protein complex is a guanine nucleotide exchange factor, meaning it helps to activate another protein called eIF2 by facilitating the exchange of GDP for GTP. This activation is a crucial step in initiating protein synthesis.

The eIF2B complex plays a dual role: under normal conditions, it promotes protein synthesis by recycling eIF2 molecules; however, it can also inhibit protein synthesis by binding tightly to eIF2, converting itself into an inactive form. This precise regulation ensures that protein levels are appropriate for the cell's current state, allowing it to adapt efficiently to demands such as growth or stress.

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Chromosome location

The EIF2B3 gene is located on the short arm of chromosome 1, specifically at position 1p34.1. This precise genomic address helps scientists identify and study its role within the human genome.

Protein structure

Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Genetic variations within the EIF2B3 gene can affect the structure and function of the gamma subunit of the eIF2B protein. These changes can impair the protein's ability to properly regulate protein synthesis, potentially leading to cellular dysfunction.

The table below shows the top 7 pathogenic or likely-pathogenic variants currently classified in ClinVar for EIF2B3.
View all on ClinVar →

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
single nucleotide variant
 p.Ile346Thr Pathogenic/Likely pathogenic ★★☆☆ Leukoencephalopathy with vanishing white matter 3
c.260C>T
single nucleotide variant
 p.Ala87Val Pathogenic/Likely pathogenic ★★☆☆ Leukoencephalopathy with vanishing white matter 3
c.674G>A
single nucleotide variant
 p.Arg225Gln Pathogenic/Likely pathogenic ★★☆☆ Leukoencephalopathy with vanishing white matter 3
c.89T>C
single nucleotide variant
 p.Val30Ala Pathogenic/Likely pathogenic ★★☆☆ Leukoencephalopathy with vanishing white matter 1
c.674G>C
single nucleotide variant
 p.Arg225Pro Pathogenic ★☆☆☆ Vanishing white matter disease
c.1193_1194del
Microsatellite
 p.Val398fs Pathogenic - Leukoencephalopathy with vanishing white matter 3
c.80T>A
single nucleotide variant
 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

Variants in the EIF2B3 gene are primarily associated with leukoencephalopathy with vanishing white matter. This condition is characterised by the progressive degeneration of the brain's white matter, which is composed of nerve fibres covered by myelin.

No disease links recorded for this gene in our reference set.

UK clinical status

The EIF2B3 gene is included in several NHS Genomic Medicine Service approved panels for inherited conditions in the UK. These include panels for ataxia and cerebellar anomalies (childhood onset), early onset or syndromic epilepsy, foetal anomalies (R21), hereditary ataxia (adult onset), inherited white matter disorders, leukodystrophy (adult onset), and neurodegenerative disorders (adult onset).

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Fetal anomalies · R21 NHS GMS → Leukodystrophy, adult onset · R62 NHS GMS → Ataxia and cerebellar anomalies - childhood onset NHS GMS → Early onset or syndromic epilepsy NHS GMS → Hereditary ataxia, adult onset NHS GMS → Neurodegenerative disorders, adult onset NHS GMS → White matter disorders and cerebral calcification - childhood onset NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary function of the EIF2B3 gene?

The EIF2B3 gene provides instructions for making the gamma subunit of the eIF2B protein, which is critical for regulating the initiation of protein synthesis within cells.

How do EIF2B3 gene variants affect health?

Variants in the EIF2B3 gene can lead to impaired function of the eIF2B protein complex, disrupting the delicate balance of protein production and affecting cellular responses to stress. This is often associated with conditions like leukoencephalopathy with vanishing white matter.

Which conditions are associated with EIF2B3?

EIF2B3 variants are primarily associated with leukoencephalopathy with vanishing white matter, a neurological disorder affecting the brain's white matter.

References

  1. Fogli A, Boespflug-Tanguy O. The large spectrum of eIF2B-related diseases. Biochemical Society transactions. 2006. PMID: 16246171
  2. Scheper GC, Proud CG, van der Knaap MS. Defective translation initiation causes vanishing of cerebral white matter. Trends in molecular medicine. 2006. PMID: 16545608
  3. 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
  4. 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
  5. 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
  6. Dietrich J, Lacagnina M, Gass D. EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy. Nature medicine. 2005. PMID: 15723074
  7. 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
  8. Pavitt GD. eIF2B, a mediator of general and gene-specific translational control. Biochemical Society transactions. 2005. PMID: 16246152
  9. 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
  10. 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
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 13 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .