| TUBA4A — Tubulin Alpha 4A | |
|---|---|
| Symbol | TUBA4A |
| Full Name | Tubulin Alpha 4A |
| Chromosome | 2q35 |
| NCBI Gene | 7277 |
| Ensembl | ENSG00000127824 |
| OMIM | 191110 |
| UniProt | P68366 |
| Diseases | Amyotrophic Lateral Sclerosis, Primary Lateral Sclerosis |
| Expression | Cerebral cortex, Spinal cord, Motor neurons |
| Key Mutations | |
| Phe384Leu Ala365Thr Glu296Lys Arg215Cys |
|
Tuba4A Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
TUBA4A (Tubulin Alpha 4A) is a gene encoding a member of the alpha tubulin family that is highly expressed in neurons and is critical for microtubule structure and function. Mutations in TUBA4A are associated with amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders[1].
TUBA4A encodes the alpha-4A tubulin protein, which is a fundamental component of microtubules — cylindrical structures that provide structural support and facilitate intracellular transport in neurons. Microtubules are essential for:
The TUBA4A protein undergoes various post-translational modifications including acetylation, glutamylation, and tyrosination, which regulate its interaction with microtubule-associated proteins and motor proteins[2].
TUBA4A mutations were first identified in ALS patients in 2014. Pathogenic variants in TUBA4A account for approximately 1-2% of familial ALS cases. The mutations affect microtubule stability and impair axonal transport, leading to progressive motor neuron degeneration[1:1].
The most common pathogenic mutations include:
Some TUBA4A mutations have been associated with upper motor neuron predominant disorders, including PLS, which shares features with ALS but spares lower motor neurons[3].
TUBA4A represents a potential therapeutic target for ALS:
The study of Tuba4A Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Wu CH, Fallini C, Ticozzi N, et al. Mutations in the tubulin alpha-4A subunit gene (TUBA4A) in familial and sporadic amyotrophic lateral sclerosis. Neuron. 2014;81(2):312-319. PMID:24462097 ↩︎ ↩︎
Janke C, Kneussel M. Tubulin post-translational modifications: emerging functions in neuronal trafficking. Neuroscientist. 2010;16(3):266-275. PMID:20236956 ↩︎
Oberstadt M, Claussen S, Stribl C, et al. TUBA4A-related disorders: broadening the phenotypic spectrum of tubulinopathies. Acta Neuropathol Commun. 2021;9(1):85. PMID:34006354 ↩︎