ATXN3 (Ataxin-3) variants and mutations

ATXN3 (also known as Ataxin-3) is a human protein-coding gene encoding an ataxin-3 protein. It functions as a deubiquitinating enzyme involved in protein-quality control and ubiquitin signaling. Expansion of its polyglutamine tract causes spinocerebellar ataxia type 3, also called Machado-Joseph disease, through toxic protein misfolding and neurodegeneration. This analysis covers 545 ATXN3 variants and mutations. Of these, 74% have computational variant effect predictions. Disease context includes Machado-Joseph disease, Spinocerebellar ataxia type 3, and Abnormality of the skeletal system. Example ATXN3 variants include M1?, E2A, and E2K.

Variant analysis overview

Gene: ATXN3
Protein: Ataxin-3
UniProt accession: P54252
Organism: Homo sapiens
Variants analyzed: 545
Variant scope: all variants
Completed: 2026-08-22

Variant and mutation evidence

Variant composition: 398 unspecified-consequence records; 7 stop lost; 30 synonymous variants; 83 missense variants; 17 frameshift variants; 5 stop-gained variants; 3 splice-region variants; 1 stop retained variant; 8 in-frame deletions; 3 in-frame insertions; 2 substitution
Prediction scores: 404 variants have prediction scores (74% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: Machado-Joseph disease, Spinocerebellar ataxia type 3, Abnormality of the skeletal system, Machado-Joseph disease type 1, Machado-Joseph disease type 2, Machado-Joseph disease type 3, Parkinson disease, late-onset Parkinson disease, Hereditary late-onset Parkinson disease, hereditary disease, Tip-toe gait, multiple system atrophy, cerebellar type.

Protein structure and variant hotspots

Protein features: 4 domains; 4 post-translational modification sites.
Structural context: 324 variants have structural context.
PTM context: 5 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable ATXN3 variants

Examples include M1?, E2A, E2K, S3Y, I4L, I4V, H6P, H6Y. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

ATXN3 analysis run — ATXN3 (545 variants) — completed 2026-08-22