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TUBB4A gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

TUBB4A gene

The TUBB4A gene provides instructions for making a protein critical for brain development and structure, with mutations linked to leukodystrophy and movement disorders.

Normal Function

The TUBB4A gene provides instructions for making a protein called beta-tubulin (β-tubulin). This protein is part of the tubulin family of proteins that form and organize structures called microtubules. Microtubules are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). They are composed of β-tubulin and a similar protein called alpha-tubulin (α-tubulin) that is produced from a different gene.

The β-tubulin protein produced from the TUBB4A gene is found primarily in the brain, particularly in regions called the basal ganglia (specifically a part called the putamen) and the cerebellum. These regions help control movement. The protein is also found extensively in the brain's white matter, which consists of nerve fibers covered by a fatty substance called myelin that insulates and protects them. During brain development, microtubules help move nerve cells (neurons) to their proper location (neuronal migration). The microtubules also form scaffolding within neurons that provides structure and aids in the transport of substances.

Health Conditions Related to Genetic Changes

TUBB4A-related leukodystrophy

More than 30 mutations in the TUBB4A gene cause TUBB4A-related leukodystrophy. This disorder is characterized by abnormalities of the white matter, particularly a reduced ability of the nervous system to produce myelin (hypomyelination). TUBB4A-related leukodystrophy has a wide range of severity, with a condition called hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) at the most severe end of the spectrum and isolated hypomyelination at the mildest end. In addition to hypomyelination, affected individuals can have breakdown (atrophy) of brain tissue, movement abnormalities, difficulty swallowing and speaking, and learning problems.

The mutations that cause TUBB4A-related leukodystrophy change single amino acids in the β-tubulin protein. H-ABC is most commonly caused by a mutation that replaces the amino acid aspartate with the amino acid asparagine at protein position 249 (Asp249Asn or D249N). These mutations are thought to alter the structure of the β-tubulin protein, likely impairing the formation or stability of microtubules. Researchers suspect that problems with microtubules impair neuronal migration or the transport of important substances within neurons, which may lead to dysfunction and loss of these cells in the brain.

Other disorders

At least two TUBB4A gene mutations have been found to cause another neurological disorder called dystonia 4 (also known as DYT4 dystonia or whispering dysphonia), which is characterized by a weak, whispery voice (dysphonia) that typically begins in adulthood. Affected adults later develop involuntary muscle contractions (dystonia), difficulty walking, and sometimes swallowing problems (dysphagia). Individuals with dystonia 4 do not have hypomyelination or other brain abnormalities like those that occur in people with TUBB4A-related leukodystrophy.

The most common TUBB4A gene mutation that causes dystonia 4 replaces the amino acid arginine with the amino acid glycine at protein position 2 (Arg2Gly or R2G). These mutations are thought to disrupt the structure of the β-tubulin protein and, consequently, the formation or stability of microtubules.

Other Names for This Gene

  • beta-5
  • dystonia 4, torsion (autosomal dominant)
  • DYT4
  • TUBB4
  • tubulin beta-4 chain
  • tubulin beta-4A chain isoform 1
  • tubulin beta-4A chain isoform 2
  • tubulin beta-4A chain isoform 3
  • tubulin beta-4A chain isoform 4
  • tubulin, beta 4
  • tubulin, beta, 5

Frequently Asked Questions

Currently, there is no cure for TUBB4A-related leukodystrophy, and treatment focuses on managing symptoms and improving quality of life. This often involves a multidisciplinary approach including physical therapy, occupational therapy, and speech therapy to address movement and communication challenges. Medications may be used to manage symptoms like spasticity or dystonia. Regular monitoring by neurologists is also important.
Diagnosis usually involves a combination of clinical evaluation, brain imaging, and genetic testing. Magnetic resonance imaging (MRI) of the brain is crucial, as it can reveal characteristic white matter abnormalities and hypomyelination, especially in the basal ganglia and cerebellum. Genetic testing confirms the diagnosis by identifying specific mutations in the TUBB4A gene.
TUBB4A-related leukodystrophy, particularly the severe H-ABC form, often presents in infancy or early childhood with movement problems like difficulty coordinating movements (ataxia), muscle stiffness (spasticity), and involuntary movements (dystonia). Developmental delays, speech difficulties, and problems with balance can also be early indicators. The severity varies, with milder forms potentially having less noticeable symptoms.
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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