SCA3_ATXN3
- Gene
- ATXN3
- Disease
- SCA3
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 17.5
- Publications Reviewed
- 9
- Publication Span
- 29.5 years
- Last Updated
- 08/12/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt, Harriet Dashnow
Description
Spinocerebellar ataxia type 3 (SCA3/Machado-Joseph disease) is an autosomal dominant polyglutamine neurodegenerative disorder caused by a heterozygous CAG repeat expansion in ATXN3. The disorder is characterized by progressive cerebellar ataxia with variable pyramidal, extrapyramidal, peripheral motor neuron, ophthalmologic, and other neurologic features. Reported normal alleles are generally much shorter than pathogenic alleles, and multiple studies support a repeat-length effect, with larger expanded alleles associated with earlier age at onset and anticipation.
Genetic evidence
Total: 12
| Singular Evidence | Probands | PMID:7573040 | 3 | Four unrelated French families were studied; all showed expanded CAG repeats and the SCA3/MJD phenotype. |
| Singular Evidence | Probands | PMID:8619527 | 3 | Thirty-four families with confirmed SCA3/MJD were clinically characterized, demonstrating broad phenotypic variability. |
| Collective Evidence | Allele | PMID:9040742 PMID:7573040 | 2 | PMID 9040742 reports that in four Chinese MJD/SCA3 pedigrees, all 15 affected individuals had expanded ATXN3/MJD1 CAG alleles of 72-86 repeats versus 14-40 repeats in normal alleles, with a significant inverse correlation between expanded repeat length and age at onset and anticipation across generations. PMID 7573040 also found a significant negative correlation between expanded repeat length and age at onset in 28 individuals from three families of French descent. |
| Statistics | Case-control data | PMID:40178277 PMID:39921113 PMID:39731318 | 6 | Available uploaded sources include molecularly confirmed SCA3 cohorts with comparison controls: 128 SCA3 patients and 125 controls with normal CAG-repeat ranges (pmid:40178277), 45 SCA3 patients and 44 controls (pmid:39921113), and 281 unrelated genetically confirmed SCA3 patients with 182 controls plus a 96-patient phenotyped cohort with expanded ATXN3 CAG alleles of 56-84 repeats (pmid:39731318). These studies provide patient-control cohort context but are not primary discovery case-control enrichment studies. |
Experimental evidence
Total: 5.5
| Function | Biochemical function | PMID:22133674 | 0.5 | This study shows that ATXN3 is a deubiquitinating enzyme involved in ubiquitin-mediated proteostasis. |
| Function | Protein interaction | PMID:19811945 | 0.5 | The study shows evidence of ATXN3 interaction, aggregation, and sequestration mechanisms. |
| Function | Regulatory impact | PMID:19811945 | 0.5 | Evidence of altered transcriptional regulation and DNA-binding ability. |
| Models | Non-human model organism | PMID:17953484 | 4 | Drosophila and C. elegans models both exhibit disease phenotypes and have been used to study disease mechanisms. |
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.