Curation SCA8 ATXN8OS

Gene ATXN8OS

Disease SCA8

Inheritance AD

Score

6 + 5.5 = 11.5 / 18

Genetic + experimental = total

Classification

Definitive

Refuted

Moderate

Definitive

Last Updated 08/12/2025

Pubs Reviewed 3

Publication Span 22.61 years

Publication Interval 22.61 years

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.

All criTRia Curations Locus Page

Genetic evidence

Total: 6

Per page

Category	Type	Citation	Score	Details
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.

Experimental evidence

Total: 5.5

Per page

Category	Type	Citation	Score	Details
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.

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