ArticleHuman mutation2013
Comparative analysis and functional mapping of SACS mutations reveal novel insights into sacsin repeated architecture.
Article in Human mutation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- The isolated HEPN domain of SACSIN exhibits RNA-binding activity.Cellular and molecular life sciences : CMLS · 2026Article
- Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay in Two Half-Siblings.Annals of clinical and translational neurology · 2026Article
- Identification of a novel SACS gene mutation leading to spastic ataxia Charlevoix-Saguenay type: a case report.Journal of medical case reports · 2025Article
- Modeling sacsin depletion in Danio Rerio offers new insight on retinal defects in ARSACS.Neurobiology of disease · 2025Article
- ARSACS: Clinical Features, Pathophysiology and iPS-Derived Models.Cerebellum (London, England) · 2025Review
- Editorial: Translational research in hereditary spastic paraplegias: filling the diagnosis gap and therapeutic perspectives.Frontiers in neuroscience · 2025Article
- Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay with Early-Onset Epilepsy and Novel Clinical Features:Sultan Qaboos University medical journal · 2025Article
- Clinical and genetic variability among Bulgarian patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay.Molecular genetics & genomic medicine · 2024Article
- Proteomics and lipidomic analysis reveal dysregulated pathways associated with loss of sacsin.Frontiers in neuroscience · 2024Article
- The J Domain of Sacsin Disrupts Intermediate Filament Assembly.International journal of molecular sciences · 2022Article
- Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations inBiomolecules · 2022Article
- Genetics of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Role of Sacsin in Neurodegeneration.International journal of molecular sciences · 2022Review
- AlphaFold predicted structure of the Hsp90-like domains of the neurodegeneration linked protein sacsin reveals key residues for ATPase activity.Frontiers in molecular biosciences · 2022Article
- Assessment of Sacsin Turnover in Patients With ARSACS: Implications for Molecular Diagnosis and Pathogenesis.Neurology · 2021Article
- Hsp90 Inhibition: A Promising Therapeutic Approach for ARSACS.International journal of molecular sciences · 2021Article
- Efficient Neuroprotective Rescue of Sacsin-Related Disease Phenotypes in Zebrafish.International journal of molecular sciences · 2021Article
- A novel homozygous SACS mutation identified by whole exome sequencing-genotype phenotype correlations of all published cases.Journal of molecular neuroscience : MN · 2020Review
- Sacs R272C missense homozygous mice develop an ataxia phenotype.Molecular brain · 2019Article
- Clinical and molecular studies in two new cases of ARSACS.Neurogenetics · 2019Article
- Structures of ubiquitin-like (Ubl) and Hsp90-like domains of sacsin provide insight into pathological mutations.The Journal of biological chemistry · 2018Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurological disease with mutations in SACS, encoding sacsin, a multidomain protein of 4,579 amino acids. The large size of SACS and its translated protein has hindered biochemical analysis of ARSACS, and how mutant sacsins lead to disease remains largely unknown. Three repeated sequences, called sacsin repeating region (SRR) supradomains, have been recognized, which contribute to sacsin chaperone-like activity. We found that the three SRRs are much larger (≥1,100 residues) than previously described, and organized in discrete subrepeats. We named the large repeated regions Sacsin Internal RePeaTs (SIRPT1, SIRPT2, and SIRPT3) and the subrepeats sr1, sr2, sr3, and srX. Comparative analysis of vertebrate sacsins in combination with fine positional mapping of a set of human mutations revealed that sr1, sr2, sr3, and srX are functional. Notably, the position of the pathogenic mutations in sr1, sr2, sr3, and srX appeared to be related to the severity of the clinical phenotype, as assessed by defining a severity scoring system. Our results suggest that the relative position of mutations in subrepeats will variably influence sacsin dysfunction. The characterization of the specific role of each repeated region will help in developing a comprehensive and integrated pathophysiological model of function for sacsin.
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