Ataxin-7 (ATXN7)

Ataxin-7 is a chromatin-modifying protein that functions as an essential subunit of the SAGA (Spt-Ada-Gcn5 acetyltransferase) transcription coactivator complex, where it enables proper histone acetylation and deubiquitination, thereby regulating gene expression[1][6][8]. It is uniquely characterized by an N-terminal polyglutamine tract, whose expansion due to CAG repeat mutations causes the neurodegenerative disease spinocerebellar ataxia type 7 (SCA7)[2][6][7]. In its mutant (polyglutamine-expanded) form, ataxin-7 misfolds and aggregates, forming nuclear inclusions and disrupting transcription, particularly affecting neuronal and retinal cells. Ataxin-7 also plays cytoplasmic roles by associating with and stabilizing microtubules, contributing to cellular structure maintenance[3][5][7]. There are currently no approved drugs that directly target ATXN7; therapeutic approaches focus primarily on gene silencing or aggregation inhibition. Defects in ATXN7 function or aggregation lead to progressive cerebellar ataxia, retinal degeneration, and multisystem neurodegeneration[6][7][8].

Other names

SCA7OPCA3ADCAIISGF73Spinocerebellar ataxia type 7 proteinAutosomal dominant cerebellar ataxia with retinal degenerationSAGA-associated factor 73 kDa homologSpt3-TAF9-GCN5 acetyltransferase subunitSpt-Ada-Gcn5 acetyltransferase complex subunitataxin-7

Disease-modifying approaches would theoretically include inhibition of pathological polyglutamine tract expansion, reduction of mutant protein aggregation, promoting cellular clearance of mutant ATXN7, or modulating its interaction with chromatin-modifying complexes.