TUBA1A

TUBA1A, or tubulin alpha-1A chain, is a human gene that encodes the alpha-1A tubulin protein, a member of the tubulin family and a core component of microtubules in eukaryotic cells. The protein is roughly 450 amino acids in length and forms heterodimers with beta-tubulin to polymerize microtubules, which are dynamic structures essential for cell shape, intracellular transport, mitosis, and, in the developing brain, neuronal migration.

In neurons, microtubules provide tracks for organelle movement and are involved in axon growth and dendrite formation. The alpha-tubulin subunit binds GTP and, together with beta-tubulin, contributes to microtubule stability and dynamics that drive remodeling during development. TUBA1A belongs to the canonical tubulin alpha family and is expressed with higher levels during brain development, aligning with its role in neuronal maturation.

Mutations in TUBA1A cause tubulinopathies, a spectrum of brain malformations resulting from impaired microtubule function. Most reported variants are de novo heterozygous missense changes. Clinical features include lissencephaly or pseudo-lissencephaly, simplified gyral patterns, pachygyria, cerebellar hypoplasia, corpus callosum abnormalities, seizures, and developmental delay. Phenotypes vary with the mutation's position and effect on tubulin folding and microtubule interactions. Diagnosis is based on genetic testing and neuroimaging; management is supportive and multidisciplinary.

Genetically, TUBA1A is one gene among several alpha-tubulin family members. The protein participates in interactions with microtubule-associated proteins and motor proteins, and post-translational modifications regulate its incorporation into microtubules and lattice stability. Research on TUBA1A contributes to understanding cortical development and the molecular basis of tubulinopathies.