SCA8_ATXN8OS
- Gene
- ATXN8OS
- Disease
- SCA8
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 11.5
- Publications Reviewed
- 3
- Publication Span
- 22.61 years
- Last Updated
- 08/12/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt, Harriet Dashnow
Description
SCA8 is associated with a dominantly inherited CTG•CAG repeat expansion at the ATXN8OS/ATXN8 locus. Evidence includes expanded alleles in SCA8 families with reduced penetrance, enrichment of CCG•CGG interruptions in higher-penetrance families, bidirectional transcription producing noncoding CUG-containing ATXN8OS RNA and CAG/polyglutamine products, and cell/model data supporting RNA and protein gain-of-function mechanisms.
Genetic evidence
Total: 6
| Singular Evidence | Probands | PMID:34632710 | 6 | Large SCA8 cohort of 77 families including 199 expansion carriers (111 affected, 88 asymptomatic); 10 families showed autosomal-dominant inheritance and CCG•CGG interruptions were enriched in families with multiple affected individuals. |
1 rows
Experimental evidence
Total: 5.5
| Function | Biochemical function | PMID:10192387 | 0.5 | ATXN8OS is transcribed through the SCA8 CTG repeat as a processed, untranslated CUG-containing RNA; brain/cerebellar expression supports a locus-specific RNA function. |
| Function | Regulatory impact | PMID:10192387 | 0.5 | Supports ATXN8OS transcription and possible antisense regulatory biology. |
| Function | Regulatory impact | PMID:10192387 | 1.5 | Strand-specific RT-PCR/RACE showed the CTG repeat is in a spliced, polyadenylated ATXN8OS transcript expressed in brain and overlapping an opposite-strand transcript, supporting locus-specific regulatory impact. |
| Models | Non-human model organism | PMID:16804541 | 2 | A transgenic SCA8 mouse model was created with the full-length human SCA8 (CTG)116 expansion transcribed under its endogenous promoter. The mice developed a progressive neurological phenotype and reduced cerebellar-cortical inhibition. |
| Models | Cell culture | PMID:34632710 | 1 | Patient-derived repeat constructs in T98/HEK293T cells showed CCG•CGG interruptions increased cell toxicity, p-eIF2α activation, and polyAla/polySer RAN protein levels independent of RNA abundance. |
5 rows
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.