The site of phosphorylation is the serine at the 776th residue in ataxin 1. Similar to those that lack 14-3-3 proteins, mice with this residue replaced with alanine do not exhibit cerebellar syndrome. Similarly, removal of the AXH domain from ataxin 1 prevents aberrant interactions with growth factor independent transcription repressor 1 that leads to GFI1 degradation in the proteasome. The expanded polyglutamine region results in increased affinity of the ataxin 1 AXH domain for certain transcription factors, and this effect is believed to play a significant role in ataxin 1 toxicity. Another protein shown to have significant interactions with ataxin 1 is the leucine-rich acidic nuclear protein or LANP. Its function is unknown, but it is predominately expressed in the same neurons as ataxin 1 and has been shown to localize in the nuclei of these neurons at the same substructures as ataxin 1. LANP only interacts with the polyglutamine region of ataxin 1, and its interactions are stronger as the number of glutamine residues increases, so the two proteins are likely vital to each others functions in neurons and LANP may also facilitate pathology of mutant ataxin 1 proteins. Ataxin 1 like, also called Brother of Ataxin 1 or Boat, has significant interactions with ataxin-1 and many associated proteins, like N-CoR. Ataxin 1 like has reduced expression in transgenic mice models and has been shown to moderate cytotoxicity of ataxin-1.Toxicity from the mutated protein causes degradation in neural tissues.
The volume loss can be correlated to severity and duration.An estimated 77% of cases of progressive cerebellar disease are reported to have one or more mental health disorders, and 19% exhibit cognitive disorders. These estimates are consistently higher than the portion with mental health disorders in the general population, but still follow other general patterns, like correlations between depression frequency and sex or age. It is unclear if depression can be linked causally to cerebellar degeneration; one study reports data consistent with depression primarily being a response to the disability, not a symptom of it, while another reports evidence that depression may have a causal link; prevalence of depression varies differently between SCA types than does the rate of progression of disability. Genetics
Spinocerebellar ataxia type 1 is caused by a mutation in the ATXN1 gene. This mutation is passed down through an autosomal dominant inheritance pattern, meaning that the disease does not skip generations, at least one parent must have the disease for the children to inherit it, and that the odds of any given child inheriting SCA 1, regardless of gender or other phenotypes, is 50% if the affected parent is heterozygous. : 26  The ATXN1 gene on chromosome 6 encodes the ataxin 1 protein, which is used in signaling pathways and gene regulation, and is heavily expressed in Purkinje neurons. The coding region for Ataxin 1 (6p22.3) contains a polyglutamine tract of variable length.