ATXN3

Chr 14ADMulti

ataxin 3

Also known as: AT3, ATX3, JOS, MJD, MJD1, SCA3

NCBI Gene: 4287 ENSG00000066427 UniProt: P54252 OMIM: 607047

The protein functions as a deubiquitinating enzyme that maintains protein homeostasis by trimming long polyubiquitin chains and regulating transcription, autophagy, and mTORC1 signaling. CAG repeat expansions from the normal 12-44 to 52-86 repeats cause Machado-Joseph disease (spinocerebellar ataxia-3), an autosomal dominant neurodegenerative disorder with earlier age of onset correlating with higher repeat numbers. The pathogenic mechanism involves a dominant-negative effect of the mutant protein.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Machado-Joseph disease, also known as spinocerebellar ataxia-3, is an autosomal dominant neurologic disorder. The protein encoded by this gene contains (CAG)n repeats in the coding region, and the expansion of these repeats from the normal 12-44 to 52-86 is one cause of Machado-Joseph disease. There is a negative correlation between the age of onset and CAG repeat numbers. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Parkinson disease, late-onset, susceptibility to}MIM #168600

ADMulti

Machado-Joseph diseaseMIM #109150

UniProtSpinocerebellar ataxia 3

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.49

LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — ATXN3