Curation DRPLA ATN1

Gene ATN1

Disease DRPLA

Inheritance AD

Score

8 + 4.5 = 12.5 / 18

Genetic + experimental = total

Classification

Definitive

Refuted

Moderate

Definitive

Last Updated 05/22/2026

Pubs Reviewed 5

Publication Span 43.61 years

Publication Interval 43.61 years

Curator(s) Macayla Weiner, Laurel Hiatt, Harriet Dashnow

Description

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder associated with expansion of the ATN1 CAG repeat, which encodes an expanded polyglutamine tract. The uploaded evidence includes a clinical-neuropathologic series of five families with myoclonus, epilepsy, dementia, ataxia and choreoathetosis with dentatorubral-pallidoluysian degeneration, and a molecular study showing ATN1 gene structure, ubiquitous 4.5 kb transcript expression, and predicted protein motifs. A TR-specific humanized ATN1 expansion mouse model recapitulates relevant phenotypes, and ASO treatment rescues several disease phenotypes in this model.

All criTRia Curations Locus Page

Genetic evidence

Total: 8

Per page

Category	Type	Citation	Score	Details
Singular Evidence	Probands	PMID:6808417	6	Five families with hereditary dentatorubral-pallidoluysian atrophy were described; 16 patients were clinically summarized, with autosomal dominant inheritance inferred from multigenerational parent-to-child transmission.
Collective Evidence	Allele	PMID:8136826 PMID:7778850	2	An inverse correlation has been observed between the age at onset and the size of the expanded ATN1 CAG repeat in individuals with DRPLA.

Experimental evidence

Total: 4.5

Per page

Category	Type	Citation	Score	Details
Function	Regulatory impact	PMID:7842016	0.5	Northern blot analysis detected a single 4.5 kb ATN1 transcript in all examined human tissues; after beta-actin normalization, expression varied within ~5-fold and was relatively high in brain, ovary, testis, and prostate.
Models	Non-human model organism	PMID:41624332	2	Humanized ATN1 expansion mouse model in which one allele of mouse Atn1 is completely replaced by human ATN1 with a pure 112 CAG repeat expansion. The model recapitulates relevant phenotype including behavioral alterations, reduced brain size, and aggregate accumulation.
Rescue	Rescue in non-human model organism	PMID:41624332	2	Treatment of a humanized ATN1 expansion mouse model with human ATN1-targeting ASOs rescue several disease phenotypes including behavioral phenotypes and transcriptional dysregulation in the cerebellum.

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