Curation SCA17 TBP

Gene TBP

Disease SCA17

Inheritance AD

Score

10 + 3.5 = 13.5 / 18

Genetic + experimental = total

Classification

Definitive

Refuted

Moderate

Definitive

Last Updated 08/18/2025

Pubs Reviewed 7

Publication Span 19.06 years

Publication Interval 19.06 years

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.

All criTRia Curations Locus Page

Genetic evidence

Total: 10

Per page

Category	Type	Citation	Score	Details
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

Per page

Category	Type	Citation	Score	Details
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.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.