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EIF2B2

eukaryotic translation initiation factor 2B subunit beta

The EIF2B2 gene provides instructions for producing a component of the eIF2B protein, which is critical for regulating overall protein production within cells. EIF2B2 is responsible for encoding the beta subunit of the eukaryotic translation initiation factor 2B (eIF2B) protein complex.

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 codes for one of the five subunits of the eukaryotic translation initiation factor 2B (eIF2B) protein. This protein complex acts as a critical regulator of protein synthesis in human cells.

Maintaining appropriate levels of protein synthesis is essential for cellular function, allowing cells to adapt to varying conditions, such as growth or rest. Impaired eIF2B function can disrupt this delicate balance, leading to health issues.

What the gene does

The EIF2B2 gene specifically directs the production of the beta subunit of the eIF2B protein. The eIF2B complex helps control the initiation phase of protein synthesis, a process where genetic information is translated into proteins.

It achieves this by interacting with another protein, eIF2. Under specific cellular conditions, eIF2B promotes protein synthesis by recycling molecules called GTP, which provide energy for the initiation factor. Conversely, eIF2B can slow protein synthesis by tightly binding to eIF2, rendering eIF2B inactive and preventing GTP recycling. This precise regulation ensures cells produce proteins at the correct rate to meet their changing demands.

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Chromosome location

The EIF2B2 gene is situated on the long arm of chromosome 14, at position 14q24.3. This specific genomic location helps define where the gene is found within the human genome.

Protein structure

The EIF2B2 gene encodes a protein consisting of 351 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Genetic variations within the EIF2B2 gene can influence its function. These variations range from single nucleotide changes to larger alterations, potentially affecting the production or activity of the eIF2B beta subunit. Understanding these genetic changes is important for investigating their impact on cellular processes.

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.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.818A>G
single nucleotide variant
 p.Lys273Arg Pathogenic/Likely pathogenic ★★☆☆ Leukoencephalopathy with vanishing white matter 2
c.871C>T
single nucleotide variant
 p.Pro291Ser Pathogenic ★★☆☆ Vanishing white matter disease
c.910G>T
single nucleotide variant
 p.Glu304Ter Pathogenic/Likely pathogenic ★★☆☆ Vanishing white matter disease
c.922G>A
single nucleotide variant
 p.Val308Met Pathogenic/Likely pathogenic ★★☆☆ Leukoencephalopathy with vanishing white matter 2

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 are associated with leukoencephalopathy with vanishing white matter. Some affected individuals may experience an ovarian failure variant of this condition, known as ovarioleukodystrophy, which includes neurological features alongside ovarian dysfunction. These genetic changes are thought to result in a partial loss of eIF2B function.

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 national test panels. These panels cover conditions such as Ataxia and cerebellar anomalies - childhood onset, Bilateral congenital or childhood onset cataracts, Early onset or syndromic epilepsy, Foetal anomalies, Hereditary ataxia, Hereditary ataxia, adult onset, Inherited white matter disorders, Leukodystrophy, adult onset, Neurodegenerative disorders, adult onset, and White matter disorders and cerebral calcification - childhood onset, indicating its recognised clinical importance within the UK.

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 primary function of the EIF2B2 gene?

The EIF2B2 gene provides instructions for making the beta subunit of the eIF2B protein, which is crucial for regulating the initiation phase of protein synthesis in cells.

What health conditions are associated with EIF2B2 gene variants?

Variants in the EIF2B2 gene are primarily associated with leukoencephalopathy with vanishing white matter, and in some cases, ovarioleukodystrophy.

Where is the EIF2B2 gene located?

The EIF2B2 gene is located on chromosome 14, specifically at position 14q24.3.

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