DRPLA_ATN1
- Gene
- ATN1
- Disease
- DRPLA
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 12.5
- Publications Reviewed
- 5
- Publication Span
- 43.61 years
- Last Updated
- 05/22/2026
- 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.
Genetic evidence
Total: 8
| 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
| 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. |
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.