SCA17_TBP
- Gene
- TBP
- Disease
- SCA17
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 13.5
- Publications Reviewed
- 7
- Publication Span
- 19.06 years
- Last Updated
- 08/18/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant neurodegenerative disorder caused by CAG/CAA repeat expansion in the coding polyglutamine tract of TBP. Reported phenotypes include cerebellar ataxia, cognitive/psychiatric symptoms, chorea, dystonia, parkinsonism, and Huntington disease-like presentations. Genetic evidence includes unrelated probands with TBP expansions and population studies supporting pathogenicity of expanded alleles, although low-range alleles show reduced penetrance and uncertain thresholds. Experimental evidence supports altered TBP transcription-related function, condensate behavior, aggregation, and neurotoxicity in model systems.
Genetic evidence
Total: 10
| Singular Evidence | Probands | PMID:12805114 | 6 | Two unrelated HDL probands carried TBP CAG/CAA expansions (44 and 46 repeats) after exclusion of HTT CAG expansions; both had early-onset behavioral/gait symptoms, ataxia, and dementia, with one also showing chorea. |
| Collective Evidence | Allele | PMID:12805114 | 2 | Expanded alleles comprised 44 and 46 CAG/CAA repeats; the 46-repeat allele was inherited from an unaffected 59-year-old father, supporting reduced penetrance in the low-expansion range. |
| Statistics | Case-control data | PMID:27172828 PMID:26374734 PMID:26267067 | 2 | PMIDs 26374734 and 27172828 support association of low-range TBP expansions with SCA17/PD phenotypes in Thai cohorts, while PMID 26267067 found overlapping 41–44 repeat frequencies in Korean patients and controls; low-range alleles require cautious interpretation. |
Experimental evidence
Total: 3.5
| Function | Regulatory impact | PMID:35868859 PMID:32386547 | 1 | PMID 32386547 showed disease-associated TBP polyQ expansion altered phase-separation behavior of TBP-containing transcriptional condensates; PMID 35868859 is TAF1/XDP-focused and is not TBP/SCA17 locus-specific. |
| Functional Alteration | Non-patient cells | PMID:32386547 | 0.5 | experimental evidence using engineered constructs in non‑patient cells and in vitro systems. Pathogenic polyglutamine expansion in the TBP N‑terminal disordered region disrupts its normal phase separation behavior, providing a potential molecular mechanism for SCA17. |
| Models | Non-human model organism | PMID:18218637 | 2 | Transgenic mice expressing truncated polyQ-expanded TBP developed neuronal nuclear inclusions and severe early neurological phenotypes/early death, supporting in vivo neurotoxicity of expanded TBP. |
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.