ATXN2

ATXN2

ATXN2 (Ataxin-2) is a gene that encodes a protein involved in various cellular processes, including RNA metabolism and stress response. Mutations in this gene are associated with neurodegenerative disorders, most notably Spinocerebellar ataxia type 2 (SCA2). ATXN2 is located on chromosome 12 in humans and is expressed in many tissues, with particularly high levels in the brain.

Structure

The ATXN2 gene is composed of multiple exons and encodes a protein that contains several important domains. These include the Lsm (Like-Sm) domain, which is involved in RNA binding, and the polyglutamine tract, which is prone to expansion mutations that lead to disease.

Function

ATXN2 plays a crucial role in RNA processing and metabolism. It is involved in the regulation of mRNA stability and translation. The protein interacts with other RNA-binding proteins and is part of stress granules, which are aggregates of proteins and RNAs that form in response to cellular stress.

Clinical Significance

Mutations in the ATXN2 gene, particularly expansions of the CAG repeat in the polyglutamine tract, are linked to Spinocerebellar ataxia type 2 (SCA2). This is a progressive neurodegenerative disorder characterized by ataxia, or loss of coordination, due to degeneration of the cerebellum and other parts of the nervous system.

ATXN2 has also been implicated in Amyotrophic lateral sclerosis (ALS), where intermediate-length expansions of the CAG repeat are considered a risk factor for the disease.

Research

Ongoing research is focused on understanding the precise molecular mechanisms by which ATXN2 mutations lead to neurodegeneration. Studies are also exploring potential therapeutic approaches, such as gene silencing techniques, to mitigate the effects of pathogenic ATXN2 expansions.

Also see

• Spinocerebellar ataxia
• Polyglutamine disease
• RNA-binding protein
• Neurodegenerative disease