ATN1
Chr 12ADatrophin 1
Also known as: B37, CHEDDA, D12S755E, DRPLA, HRS, NOD
This gene encodes atrophin-1, a transcriptional corepressor that recruits other proteins to repress gene transcription and promotes vascular smooth muscle cell migration. Mutations cause dentatorubral-pallidoluysian atrophy (DRPLA), a neurodegenerative disorder with cerebellar ataxia, myoclonic epilepsy, choreoathetosis, and dementia, as well as a congenital form with hypotonia, epilepsy, developmental delay, and digital anomalies. The inheritance pattern is autosomal dominant.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
443 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 4 | 46 | 0 | 50 |
Likely Pathogenic | 0 | 7 | 3 | 0 | 10 |
VUS | 16 | 222 | 14 | 1 | 253 |
Likely Benign | 0 | 39 | 4 | 34 | 77 |
Benign | 1 | 7 | 5 | 6 | 19 |
Conflicting | — | 17 | |||
| Total | 17 | 279 | 72 | 41 | 426 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATN1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Personalized Antisense Oligonucleotide for A Single Participant With ATN1 Gene Mutation
ACTIVE NOT RECRUITINGPersonalized Antisense Oligonucleotide Therapy for A Single Participant With ATN1 Gene Mutation
ACTIVE NOT RECRUITINGPersonalized Antisense Oligonucleotide for A Single Participant (nL62541) With ATN1 Gene Mutation
ACTIVE NOT RECRUITINGDentatorubral-pallidoluysian Atrophy Natural History and Biomarkers Study
RECRUITINGExternal Resources
Links to major genomics databases and tools