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EIF2B5 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

EIF2B5 gene

The EIF2B5 gene provides instructions for the epsilon subunit of the eIF2B protein, which plays a critical role in regulating cellular protein synthesis.

Normal Function

The EIF2B5 gene provides instructions for making one of five parts of a protein called eIF2B, specifically the epsilon subunit. The eIF2B protein helps regulate overall protein production (synthesis) in the cell by interacting with another protein, eIF2. The eIF2 protein is called an initiation factor because it is involved in starting (initiating) protein synthesis.

Under some conditions, eIF2B increases protein synthesis by helping to recycle molecules called GTP, which carry energy to the initiation factor. Under other conditions, it slows protein synthesis by binding tightly to the initiation factor, which converts the eIF2B protein into an inactive form and prevents the recycling of GTP.

Proper regulation of protein synthesis is vital for ensuring that the correct levels of protein are available for the cell to cope with changing conditions. For example, cells must synthesize protein much faster if they are multiplying than if they are in a resting state.

Health Conditions Related to Genetic Changes

Leukoencephalopathy with vanishing white matter

Mutations in the EIF2B5 gene have been identified in about 65 percent of people with leukoencephalopathy with vanishing white matter, including those with a severe, early-onset form that is seen among the Cree and Chippewayan populations of Quebec and Manitoba (Cree leukoencephalopathy) and some affected females with a variant of the disorder in which the neurological features are accompanied by ovarian failure (ovarioleukodystrophy). These mutations cause partial loss of eIF2B function. Impairment of eIF2B function makes it more difficult for the body's cells to regulate protein synthesis and deal with changing conditions and stress. Researchers believe that cells in the white matter (nerve fibers covered by a fatty substance called myelin that insulates and protects nerves) may be particularly affected by an abnormal response to stress, resulting in the signs and symptoms of leukoencephalopathy with vanishing white matter.

Other Names for This Gene

  • CACH
  • CLE
  • EI2BE_HUMAN
  • EIF-2B
  • eIF-2B GDP-GTP exchange factor
  • EIF2Bepsilon
  • eukaryotic translation initiation factor 2B, subunit 5 (epsilon, 82kD)
  • eukaryotic translation initiation factor 5 epsilon, 82kDa
  • LVWM

Frequently Asked Questions

The EIF2B5 gene is the most frequently implicated gene in leukoencephalopathy with vanishing white matter (VWM), accounting for approximately 65 percent of all cases. This high prevalence is partly due to the specific role of the epsilon subunit in the eIF2B complex, where mutations in this subunit are particularly effective at disrupting the protein's ability to regulate protein synthesis under stress. The high frequency of specific pathogenic variants in this gene, especially in certain populations, contributes to its status as the primary genetic driver of the disorder compared to the other four eIF2B subunits.
Because EIF2B5 mutations cause a partial loss of eIF2B function, patients have a reduced capacity to regulate protein synthesis in response to stress. This often manifests as exercise intolerance, where physical activity or heat exposure triggers acute neurological worsening, such as increased spasticity, weakness, or confusion. Patients are generally advised to avoid overheating and strenuous exertion. Daily management involves careful monitoring of body temperature and hydration, as even minor stressors like a common cold can precipitate a significant neurological event that may require medical intervention to stabilize.
Yes, females with mutations in the EIF2B5 gene can also develop ovarioleukodystrophy, a variant of VWM characterized by the combination of neurological symptoms and premature ovarian failure. While EIF2B4 is strongly associated with this phenotype, EIF2B5 mutations have also been identified in affected females with ovarian dysfunction. This highlights that the reproductive impact of eIF2B dysfunction is not limited to a single subunit. Women with confirmed EIF2B5 mutations should be monitored for signs of ovarian insufficiency, such as irregular menstrual cycles or early menopause, as part of their comprehensive care plan.
Cree leukoencephalopathy is a severe, early-onset form of VWM that has been identified specifically among the Cree and Chippewayan populations in Quebec and Manitoba. It is caused by a specific founder mutation in the EIF2B5 gene, meaning the mutation originated from a common ancestor in that population and has been passed down through generations. This variant is notable for its rapid progression and severe neurological decline in early childhood. Recognizing this specific ethnic and genetic link is crucial for targeted screening and genetic counseling within these communities.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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