SCA1_ATXN1
- Gene
- ATXN1
- Disease
- SCA1
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 14.5
- Publications Reviewed
- 7
- Publication Span
- 36.33 years
- Last Updated
- 08/12/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt, Harriet Dashnow
Description
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by a heterozygous CAG repeat expansion in the coding region of ATXN1. The locus was first supported by linkage of autosomal dominant spinocerebellar ataxia to chromosome 6p/HLA in a large multigenerational kindred and later by identification of an unstable expanded ATXN1 CAG repeat that segregates with disease and shows repeat-length association with age at onset. Uploaded cohort studies support the clinical phenotype and biomarker profile of genetically confirmed SCA1, while mouse model studies support pathogenic gain-of-function and disease-relevant molecular and motor phenotypes.
Genetic evidence
Total: 12
| Singular Evidence | Probands | PMID:3165612 | 6 | A seven-generation autosomal dominant SCA kindred included 41 affected individuals, with 26 examined neurologically and 15 identified from medical records or family history; this is pre-ATXN1-repeat, chromosome 6p/HLA-linked SCA1-region evidence rather than repeat-specific genotyping. |
| Collective Evidence | Allele | PMID:30933216 | 2 | Population genotyping of polyglutamine disease genes defined ATXN1 intermediate alleles as 36-38 CAG repeats and pathological alleles as 39-91 CAG repeats; among 13,668 long ATXN1 alleles, 636 were intermediate and 9 were in the pathological range (39-44), but CAT interruptions were not assessed. |
| Collective Evidence | Segregation | PMID:3165612 | 1.5 | In the same seven-generation kindred, linkage analysis of a 93-member pedigree showed strong linkage of the SCA1-region disease locus to HLA loci, with maximum LOD score 5.83 at recombination fraction 0.12; this supports segregation of the linked region, not direct repeat-level segregation. |
| Statistics | Case-control data | PMID:39096063 PMID:20502998 PMID:19028133 | 6 | These studies compare genetically confirmed SCA1 individuals with controls for balance, neuropsychological features, or longitudinal biomarkers, supporting the clinical phenotype and biomarker profile of genetically confirmed SCA1. While, these studies are not ideal case-control designs, collectively, they are supportive. |
Experimental evidence
Total: 2.5
| Function | Biochemical function | PMID:8358429 | 0.5 | PMID 8358429 identified the disease-associated ATXN1-region CAG repeat within a transcribed sequence and showed the repeat is present in a ~10 kb mRNA expressed in multiple tissues, including brain and skeletal muscle; this is locus-level transcript evidence rather than direct biochemical function. |
| Rescue | Rescue in non-human model organism | PMID:35573049 | 2 | In symptomatic B05 SCA1 mice expressing polyglutamine-expanded human ATXN1, AAV-delivered human ATXN1L alone or combined with miS1 targeting mutant ATXN1 improved rotarod motor phenotypes and partially normalized disease-associated cerebellar gene-expression changes. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.