Senataxin mutations in ALS4 are presumably gain-of-function, as loss-of-function mutations in the senataxin gene are responsible for autosomal recessive Ataxia with Oculomotor Apraxia type 2 (AOA2), and AOA2 carriers do not develop motor neuron disease [33], though this does not rule out a role for altered senataxin function in ALS4 pathogenesis, as occurs in dominant polyglutamine repeat expansion disease [26]. This evidence concerns the gene SETX and motor neuron disorder.