SETX: Senataxin – A Key Helicase in DNA Repair and Neurodegeneration
Comprehensive gene card for SETX (Senataxin), including genomic annotations, expression profiles, disease associations, and functional classifications.
Gene Information Card
| Symbol | SETX |
|---|---|
| Full Name | Senataxin |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.13 |
| NCBI Gene ID | 23064 ncbi.nlm.nih.gov/gene/23064 |
| Ensembl ID | ENSG00000107290 |
| UniProt ID | Q7Z333 |
| OMIM ID | 608465 |
| HGNC ID | 10796 |
| Aliases | ALS4, AOA2, SCAR1, bA479I1.1 |
Description
SETX encodes senataxin, a DNA/RNA helicase that plays a critical role in transcription termination, DNA replication stress response, and RNA processing. Mutations in SETX are associated with two distinct neurodegenerative disorders: ataxia with oculomotor apraxia type 2 (AOA2) and amyotrophic lateral sclerosis type 4 (ALS4). The protein is involved in resolving R-loops and maintaining genomic stability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ataxia with oculomotor apraxia type 2 (AOA2) | Loss of senataxin function leads to defective transcription termination and R-loop accumulation, causing cerebellar atrophy and peripheral neuropathy. | OMIM #606002; ClinVar |
| Amyotrophic lateral sclerosis type 4 (ALS4) | Dominant missense mutations in SETX are thought to confer a gain-of-function or dominant-negative effect, leading to motor neuron degeneration. | OMIM #602433; ClinVar |
| Spinocerebellar ataxia, autosomal recessive 1 (SCAR1) | Biallelic loss-of-function mutations in SETX cause a slowly progressive ataxia with cerebellar atrophy. | OMIM #606002; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Cerebellum | 15.3 | Medium |
| Testis | 8.2 | Low |
| Heart | 6.1 | Low |
| Liver | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 10.2 | Neuroblastoma cell line |
| HeLa | 7.5 | Cervical carcinoma |
| HEK293 | 6.8 | Embryonic kidney |
| U2OS | 5.9 | Osteosarcoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3020T>C (p.Leu1007Pro) | Missense | Rare | Dominant; associated with ALS4 |
| c.4972C>T (p.Arg1658*) | Nonsense | Rare | Loss-of-function; associated with AOA2 |
| c.6028G>A (p.Gly2010Arg) | Missense | Rare | Dominant; associated with ALS4 |
| c.2921_2922del (p.Glu974Valfs*2) | Frameshift | Rare | Loss-of-function; associated with AOA2 |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift) cause AOA2 and SCAR1 by impairing helicase activity and R-loop resolution.
Gain of Function (GOF)
Dominant missense mutations in ALS4 are hypothesized to confer a toxic gain-of-function, though the exact mechanism remains under investigation.
Dominant Negative (DN)
Some ALS4-associated missense mutations may act via a dominant-negative effect, interfering with wild-type senataxin function.
View complete mutation data：
Gene Ontology (GO)
| • DNA helicase activity (GO:0003678) | • RNA helicase activity (GO:0003724) |
| • ATP binding (GO:0005524) | • Transcription termination (GO:0006353) |
| • DNA repair (GO:0006281) | • Nucleus (GO:0005634) |
Pathways
• DNA damage response
• Transcription termination by RNA polymerase II
• R-loop processing
Protein Summary
Senataxin is a 2677-amino acid protein containing a DEAD-box helicase domain and a C-terminal zinc finger. It localizes to the nucleus and is involved in resolving RNA-DNA hybrids (R-loops) that form during transcription. Senataxin also participates in DNA double-strand break repair by facilitating transcription termination at damaged sites. Its dysfunction leads to genomic instability and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SETX Knockout HEK293 Cell Line | EDJ-KQ7804 | Human | 23064 | Details Get a Quote |
| SETX Knockout A-549 Cell Line | EDJ-KQ33319 | Human | 23064 | Details Get a Quote |
| SETX Knockout HCT 116 Cell Line | EDJ-KQ33320 | Human | 23064 | Details Get a Quote |
| SETX Knockout HeLa Cell Line | EDJ-KQ33321 | Human | 23064 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
