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EIF2B4 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

EIF2B4 gene

The EIF2B4 gene encodes the delta subunit of the eIF2B protein, which is essential for the initiation and regulation of protein synthesis.

Normal Function

The EIF2B4 gene provides instructions for making one of five parts of a protein called eIF2B, specifically the delta 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 EIF2B4 gene have been identified in a few people with leukoencephalopathy with vanishing white matter, including 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

  • DKFZp586J0119
  • EI2BD_HUMAN
  • EIF-2B
  • EIF2B
  • EIF2Bdelta
  • eukaryotic translation initiation factor 2B, subunit 4 (delta, 67kD)
  • eukaryotic translation initiation factor 2B, subunit 4 delta
  • eukaryotic translation initiation factor 2B, subunit 4 delta, 67kDa
  • translation initiation factor eIF-2b delta subunit

Frequently Asked Questions

The EIF2B4 gene is associated with a specific variant of leukoencephalopathy with vanishing white matter (VWM) that can present with ovarian failure, a condition known as ovarioleukodystrophy. While the neurological symptoms such as spasticity, ataxia, and cognitive decline are similar to other VWM subtypes, the presence of premature ovarian insufficiency in affected females is a key distinguishing clinical feature. This dual involvement of the nervous system and reproductive system helps clinicians differentiate EIF2B4-related cases from those caused by mutations in other eIF2B subunits, which typically do not present with ovarian dysfunction.
Leukoencephalopathy with vanishing white matter caused by EIF2B4 mutations is inherited in an autosomal recessive pattern. This means that an individual must inherit two mutated copies of the gene, one from each parent, to develop the condition. Parents who carry one mutated copy are typically asymptomatic carriers. Genetic counseling is recommended for families with a history of the disorder to assess the risk of recurrence in future pregnancies, which is generally 25 percent for each child if both parents are carriers.
Mutations in EIF2B4 cause a partial loss of function in the eIF2B protein, which impairs the cell's ability to regulate protein synthesis during periods of stress. In healthy individuals, cells adjust protein production in response to stressors like fever, infection, or trauma. In patients with EIF2B4 mutations, this regulatory mechanism is defective, leading to an inability to cope with these physiological demands. Consequently, patients often experience acute neurological deterioration or "decompensation" during febrile illnesses, heat exposure, or physical exertion, which can result in permanent neurological damage if not managed carefully.
Diagnosis typically begins with brain magnetic resonance imaging (MRI), which reveals characteristic white matter changes, often including cystic lesions or "vanishing" white matter. However, imaging alone is not sufficient for a definitive genetic diagnosis. Confirmatory testing requires molecular genetic analysis, such as sequencing of the EIF2B4 gene, to identify specific pathogenic variants. In some cases, if sequencing is inconclusive, additional tests like deletion/duplication analysis may be performed. A multidisciplinary team including neurologists and geneticists usually coordinates this diagnostic process to ensure accurate interpretation of results.
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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