Helicases are enzymes that bind to specific regions of double stranded DNA and help unwind the DNA structure. They are thus pivotal in the process of DNA repair. Senataxin, coded by the SETX gene is one such helicase and it has been predicted to play a role in DNA and RNA processing as it has a DNA/RNA helicase domain at the C-terminus. SETX is speculated to be involved in DNA repair, RNA splice site selection, splicing efficiency, RNA Polymerase II binding and transcription termination. Mutations in senataxin generally result in a disrupted helicase domain affecting the DNA repair function and lead to an accumulation of DNA damage in cells.

Mutations in SETX have been associated with two different diseases: Ataxia and Oculomotor Apraxia 2 (AOA2) which is an autosomal recessive neurodegenerative disorder characterized by cerebellar atrophy and peripheral neuropathy; and Juvenile Amyotrophic Lateral Sclerosis 4 (ALS4), an autosomal dominant disorder resulting in distal limb weakness and amyotrophy.

SETX has been mapped to the 9q34 region of the chromosome and has 24 exons. Two prominent transcripts are produced for the gene, 11kb and 9 kb in size, have been found in most tissues. The senataxin protein contains 2677 amino acids and has a size of 302.8kDa.

Most mutations in the SETX gene leading to AOA2 syndrome are found in exon 8, thereby disrupting the C-terminus end that contains the 7-motif helical domain.