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EIF2B2

eukaryotic translation initiation factor 2B subunit beta

The EIF2B2 gene provides instructions for a subunit of the eukaryotic translation initiation factor 2B (eIF2B) protein, which is crucial for regulating protein production within cells. EIF2B2 encodes the beta subunit of the eIF2B protein, a complex that plays a central role in controlling how and when proteins are made.

Chromosome 14q24.3 Various HGNC:3258 Tier C
EIF2B2 14q24.3 p arm q arm 14

EIF2B2 is located on the long (q) arm of chromosome 14, at band 14q24.3. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 14 in the library →

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Clinical tests that include this

Carrier Screening panel
EIF2B2 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The EIF2B2 gene is responsible for producing one of the five subunits (specifically, the beta subunit) that make up the eukaryotic translation initiation factor 2B (eIF2B) protein. This eIF2B protein complex is a key regulator of overall protein synthesis, a fundamental cellular process where genetic information is translated into functional proteins.

Maintaining the correct balance of protein production is critical for cell health and function, allowing cells to respond to varying demands, such as growth or stress. Dysregulation of this process, often due to variants in genes like EIF2B2, can lead to various health conditions.

What the gene does

The EIF2B2 gene's primary role is to provide instructions for the beta subunit of the eIF2B protein. The eIF2B complex acts to recycle specific molecules essential for starting protein synthesis. This recycling involves another protein called eIF2, which initiates protein production. The eIF2B protein helps facilitate the reuse of energy-carrying GTP molecules, which are vital for this initiation step.

Depending on the cell's needs, eIF2B can either enhance protein synthesis by promoting GTP recycling or slow it down. It achieves this by binding tightly to eIF2, which renders eIF2B inactive and prevents GTP from being recycled. This regulatory mechanism allows cells to finely tune their protein production rates to adapt to different physiological states, such as rapid cell multiplication or a resting state.

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Chromosome location

The EIF2B2 gene is located on chromosome 14, specifically at position 14q24.3. This genomic address specifies its precise placement on the long arm (q arm) of chromosome 14.

Protein structure

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

Key variants

Variants within the EIF2B2 gene can alter the protein's structure and function, potentially disrupting its role in regulating protein synthesis. These genetic changes may lead to a partial loss of eIF2B function, impacting the cell's ability to produce proteins efficiently or adapt to stress. The clinical significance of EIF2B2 variants is assessed based on their impact on protein function and association with observed health conditions.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for EIF2B2.
View all on ClinVar →

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.254T>A
single nucleotide variant
 p.Val85Glu Pathogenic/Likely pathogenic ★★☆☆ Leukoencephalopathy with vanishing white matter 2
c.3G>T
single nucleotide variant
 p.Met1Ile Pathogenic/Likely pathogenic ★★☆☆ Leukoencephalopathy with vanishing white matter 2
c.512C>T
single nucleotide variant
 p.Ser171Phe Pathogenic/Likely pathogenic ★★☆☆ Vanishing white matter disease
c.514C>T
single nucleotide variant
 p.Arg172Ter Pathogenic/Likely pathogenic ★★☆☆ EIF2B2-related disorders
c.570del
Deletion
 p.Ile190fs Pathogenic/Likely pathogenic ★★☆☆ Leukoencephalopathy with vanishing white matter 2
c.599G>T
single nucleotide variant
 p.Gly200Val Pathogenic/Likely pathogenic ★★☆☆ EIF2B2-related disorder
c.607_612delinsTG
Indel
 p.Met203fs Pathogenic ★★☆☆ Leukoencephalopathy with vanishing white matter 1
c.607del
Deletion
 p.Met203fs Pathogenic/Likely pathogenic ★★☆☆ EIF2B2-related disorder
c.818A>G
single nucleotide variant
 p.Lys273Arg Pathogenic/Likely pathogenic ★★☆☆ EIF2B2-related disorder
c.871C>T
single nucleotide variant
 p.Pro291Ser Pathogenic ★★☆☆ Vanishing white matter disease

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 EIF2B2 gene have been identified in a few individuals with leukoencephalopathy with vanishing white matter. This condition is characterised by neurological features. In some affected females, it can also be accompanied by ovarian failure, a presentation known as ovarioleukodystrophy. The underlying mechanism involves a reduced function of the eIF2B protein, which impairs the body's response to stress.

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

UK clinical status

The EIF2B2 gene is included in several NHS England Genomic Medicine Service approved panels. These include panels for "Ataxia and cerebellar anomalies - childhood onset", "Bilateral congenital or childhood onset cataracts (R31)", "Early onset or syndromic epilepsy", "Foetal anomalies (R21)", "Hereditary ataxia", "Hereditary ataxia, adult onset", "Inherited white matter disorders", "Leukodystrophy, adult onset (R62)", "Neurodegenerative disorders, adult onset", and "White matter disorders and cerebral calcification - childhood onset". This indicates its recognised clinical relevance within the UK healthcare system for diagnosing these conditions.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Bilateral congenital or childhood onset cataracts · R31 NHS GMS → 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 EIF2B2 gene?

The EIF2B2 gene provides instructions for making the beta subunit of the eukaryotic translation initiation factor 2B (eIF2B) protein. This protein complex is vital for regulating the production of proteins within cells.

What conditions are associated with EIF2B2 gene variants?

Variants in the EIF2B2 gene are primarily associated with leukoencephalopathy with vanishing white matter. Some affected individuals, particularly females, may also experience ovarian failure, a condition referred to as ovarioleukodystrophy.

How does the EIF2B2 protein function in the body?

The EIF2B2 protein, as part of the eIF2B complex, helps regulate protein synthesis by recycling energy-carrying molecules (GTP) for another protein, eIF2. This enables cells to adjust their protein production rates as needed, responding to different physiological states.

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 11 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .