ATXN3 Gene (Ataxin 3)
A comprehensive guide to the ATXN3 gene, its function, associated diseases, and clinical significance.
Gene Information Card
| Symbol | ATXN3 |
|---|---|
| Full Name | Ataxin 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.12 |
| NCBI Gene ID | 4287 ncbi.nlm.nih.gov/gene/4287 |
| Ensembl ID | ENSG00000166477 |
| UniProt ID | P54252 |
| OMIM ID | 607047 |
| HGNC ID | 7106 |
| Aliases | AT3, MJD, MJD1, SCA3 |
Description
The ATXN3 gene encodes ataxin 3, a deubiquitinating enzyme involved in protein quality control and transcriptional regulation. Pathogenic expansion of a CAG trinucleotide repeat in the coding region leads to an extended polyglutamine tract, causing Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Machado-Joseph disease (SCA3) | Expanded CAG repeat (>44) results in toxic polyglutamine protein aggregation, impairing proteostasis and causing neuronal dysfunction. | OMIM #109150; ClinVar; NCBI |
| Spinocerebellar ataxia type 3 | Same as above; autosomal dominant inheritance with anticipation. | OMIM #109150; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.2 | Medium |
| Cerebellum | 15.8 | Medium |
| Testis | 8.5 | Low |
| Heart | 6.3 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 10.4 | Neuroblastoma cell line |
| HEK 293 | 9.8 | Embryonic kidney cells |
| HeLa | 7.2 | Cervical carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| CAG repeat expansion (normal: 12-44; pathogenic: >44) | Trinucleotide repeat expansion | ~1 in 100,000 (worldwide) | Gain of toxic function; protein aggregation |
| p.Ala23Val | Missense | Rare | Unknown significance; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Not established as primary mechanism; partial loss of deubiquitinase activity may contribute.
Gain of Function (GOF)
Primary mechanism: expanded polyglutamine tract confers toxic aggregation and aberrant interactions.
Dominant Negative (DN)
Possible; mutant ataxin 3 may interfere with wild-type function in heterozygotes.
View complete mutation data：
Gene Ontology (GO)
| • thiol-dependent deubiquitinase (GO:0004843) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • nucleus (GO:0005634) | • cytosol (GO:0005829) |
| • cytoplasm (GO:0005737) |
Pathways
• Ubiquitin-proteasome system
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
• Spinocerebellar ataxia (KEGG: hsa05017)
Protein Summary
Ataxin 3 is a 42 kDa deubiquitinating enzyme containing a Josephin domain and two ubiquitin-interacting motifs (UIMs). It cleaves polyubiquitin chains, regulating protein degradation and transcription. The expanded polyglutamine tract in MJD/SCA3 promotes misfolding and aggregation, leading to neuronal toxicity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATXN3 Knockout HEK293 Cell Line | EDJ-KQ5214 | Human | 4287 | Details Get a Quote |
| ATXN3L Knockout HEK293 Cell Line | EDJ-KQ10971 | Human | 92552 | Details Get a Quote |
| ATXN3 Knockout A-549 Cell Line | EDJ-KQ28223 | Human | 4287 | Details Get a Quote |
| ATXN3 Knockout HCT 116 Cell Line | EDJ-KQ28224 | Human | 4287 | Details Get a Quote |
| ATXN3 Knockout HeLa Cell Line | EDJ-KQ28225 | Human | 4287 | Details Get a Quote |
| ATXN3L Knockout HeLa Cell Line | EDJ-KQ57842 | Human | 92552 | Details Get a Quote |
| ATXN3L Knockout A-549 Cell Line | EDJ-KQ66338 | Human | 92552 | Details Get a Quote |
| ATXN3L Knockout HCT 116 Cell Line | EDJ-KQ74764 | Human | 92552 | Details Get a Quote |
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