Gene SACS
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Also known as
Sacsin Molecular Chaperone, ARSACS, DKFZp686I1726, KIAA0730Overview
SACS (Sacsin Molecular Chaperone) encodes sacsin, a very large protein that functions as a molecular chaperone and is highly expressed in the nervous system, particularly in Purkinje cells of the cerebellum and neurons of the spinal cord. Sacsin contains multiple functional domains including a DnaJ domain characteristic of Hsp40 chaperones, suggesting it plays a role in protein folding and quality control. The protein is involved in maintaining mitochondrial function and protecting neurons from oxidative stress and protein aggregation.Mutations in SACS cause autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a progressive neurodegenerative disorder originally identified in the Charlevoix-Saguenay region of Quebec, Canada, though it has since been recognized worldwide. ARSACS typically presents in early childhood with a characteristic triad of progressive cerebellar ataxia, spasticity, and peripheral neuropathy. Additional features may include retinal abnormalities with thickened nerve fiber layer and pes cavus foot deformity. The condition leads to progressive difficulty with coordination and mobility, though intellect is usually preserved. While most common in Quebec due to a founder effect, ARSACS has been identified in diverse populations globally, making SACS an important gene for genetic testing in individuals with hereditary ataxia.