Function
Probable RNA/DNA helicase involved in diverse aspects of RNA metabolism and genomic integrity. Plays a role in transcription regulation by its ability to modulate RNA Polymerase II (Pol II) binding to chromatin and through its interaction with proteins involved in transcription. Contributes to the mRNA splicing efficiency and splice site selection. Required for the resolution of R-loop RNA-DNA hybrid formation at G-rich pause sites located downstream of the poly(A) site, allowing XRN2 recruitment and XRN2-mediated degradation of the downstream cleaved RNA and hence efficient RNA polymerase II (RNAp II) transcription termination. Required for the 3' transcriptional termination of PER1 and CRY2, thus playing an important role in the circadian rhythm regulation. Involved in DNA double-strand breaks damage response generated by oxidative stress. In association with RRP45, targets the RNA exosome complex to sites of transcription-induced DNA damage. Plays a role in the development and maturation of germ cells: essential for male meiosis, acting at the interface of transcription and meiotic recombination, and in the process of gene silencing during meiotic sex chromosome inactivation (MSCI). May be involved in telomeric stability through the regulation of telomere repeat-containing RNA (TERRA) transcription. Plays a role in neurite outgrowth in hippocampal cells through FGF8-activated signaling pathways. Inhibits retinoic acid-induced apoptosis.
Gene References into Functions
- Data suggest that senataxin (SETX) functions at DNA double-strand breaks (DSBs) in order to limit translocations and ensure cell viability. PMID: 29416069
- Expression of AOA2-causative form of SETX in Drosophila muscles resulted in an alteration of translational repression of Elav. PMID: 28245518
- The pan-neuronal expression of wild-type or mutant forms of human senataxin induced morphological plasticity at neuromuscular junction synapses. PMID: 27197982
- Novel compound heterozygous mutations of SETX in Chinese AOA2 pedigree were identified, which broaden the mutation spectrum of SETX. PMID: 27644330
- The role of senataxin in regulating gene expression on a genome-wide scale in Ataxia oculomotor apraxia 2 neurons is described. PMID: 26231220
- these data indicate a potentially causal link among inborn errors in SETX, susceptibility to infection and the development of neurologic disorders. PMID: 25822250
- BRCA1/SETX complexes support a DNA repair mechanism that addresses R-loop-based DNA damage at transcriptional pause sites. PMID: 25699710
- Results identify novel genes related to senataxin function in normal and disease states. PMID: 24760770
- genetic variations in the senataxin gene may contribute to Alzheimer's disease pathogenesis in the Taiwanese Han population. PMID: 24694197
- Protein interaction analysis of senataxin and the ALS4 L389S mutant yields insights into senataxin post-translational modification and uncovers mutant-specific binding with a brain cytoplasmic RNA-encoded peptide. PMID: 24244371
- Description of a new SETX gene mutation, which when combined with a recognized SETX mutation results in ataxia with oculomotor apraxia type 2. PMID: 23566282
- This study report a Japanese SCAR1/AOA2 family with a homozygous nonsense mutation (p.Q1441X) of SETX that was identified by exome sequencing PMID: 23786967
- SETX mutations are a frequent genetic cause of juvenile and adult onset cerebellar ataxia with neuropathy and elevated serum alpha-fetoprotein. PMID: 23941260
- provide evidence that Rrp45, a subunit of the exosome, associates with SETX in a manner dependent on SETX sumoylation PMID: 24105744
- Significance of all previously reported SETX missense mutations as well as six newly identified variations in 54 patients suspected of having amyotrophic lateral sclerosis 4. PMID: 23129421
- Senataxin plays an important cellular role at the interface of transcription and the DNA damage response and that the resolution of R-loop structures is a key event in the maintenance of genome stability. PMID: 23149945
- novel missense mutation c.6406C>T (p.R2136C) in a patient with inflammatory radiculoneuropathy and amyotrophic lateral sclerosis PMID: 22577233
- This sstudy descibed that SETX gene mutation in a family diagnosed autosomal dominant proximal spinal muscular atrophy. PMID: 22088787
- Senataxin mutations in amyotrophic lateral sclerosis PMID: 21190393
- In effect, R-loops formed over G-rich pause sites, followed by their resolution by senataxin, are key steps in the termination process. PMID: 21700224
- results reveal a key role of senataxin in neuronal differentiation through the fibroblast growth factor 8 signalling and This study provided initial molecular bases to explain the neurodegeneration associated with loss-of-function mutations in senataxin. PMID: 21576111
- The partial co-localization of SETX with telomeric DNA, demonstrated by combined immunofluorescence-Q-FISH and chromatin immunoprecipitation, suggests a possible involvement of SETX in telomere stability. PMID: 21112256
- A novel nonsense truncating mutation c.6859 C > T, R2287X in SETX gene was identified in patients from one family with ataxia with oculomotor apraxia type 2. PMID: 21324166
- SETX mutations have a role in ataxia with oculomotor apraxia [case report] PMID: 19593598
- Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination. PMID: 14770181
- Missense Mutations in senataxin is associated with juvenile amyotrophic lateral sclerosis PMID: 15106121
- Four mutations in senataxin in the French-Canadian population including two novel missense mutations: the 5927T-->G mutation (L1976R), and the 193G-->A mutation(E65K). PMID: 15732101
- 2 new homozygous missense mutations in SETX, M274I & R1294C, were found.The double missense mutations are responsible for autosomal recessive ataxia-ocular apraxia 2 but not autosomal dominant juvenile ALS. PMID: 16717225
- Mother and daughter who display symptoms of cerebellar ataxia/atrophy, oculomotor defects, and tremor with mutations in syntaxin. PMID: 17096168
- defect in 2O2-induced DNA double-strand breaks repair was corrected by full-length SETX cDNA PMID: 17562789
- A patient homozygous for a novel mutation of SETX who manifested not only ataxia but also ovarian failure. PMID: 17593543
- Clinically this family presented with a phenotype combining typical features of AOA2 and ALS4; thus extending the phenotypic spectrum of SETX mutations. PMID: 18350359
- study identified a novel SETX homozygous c.5308_5311delGAGA mutation that co-segregates with autosomal recessive cerebellar ataxia with cerebellar atrophy and raised alpha-fetoprotein PMID: 18405395
- the presence of this variation in a patient with sporadic ALS, and its absence in 200 controls, supports an association between senataxin and sporadic amyotrophic lateral sclerosis PMID: 19058054
- study analysed the phenotypic spectrum of 19 ataxia with oculo-motor apraxia type 2 patients with mutations in SETX PMID: 19141356
- senataxin plays a role in coordinating transcriptional events, in addition to its role in DNA repair. PMID: 19515850
- We performed molecular analyses in six patients showing clinically an AOA2 phenotype and moderate to significant elevated serum alpha-fetoprotein levels. PMID: 19569000
- large deletions, insertions, and duplications are probably an underestimated cause for ataxia with oculomotor apraxia 2 PMID: 19744353
- Human Senataxin, is a nuclear protein involved in the DNA damage response. It is mostly located in the nucleus and nucleoplasm with less staining in the cytoplasm. It is involved in DNA single-strand break repair. PMID: 17562789
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Involvement in disease
Spinocerebellar ataxia, autosomal recessive, 1 (SCAR1); Amyotrophic lateral sclerosis 4 (ALS4)
Subcellular Location
Nucleus. Nucleus, nucleoplasm. Nucleus, nucleolus. Cytoplasm. Chromosome. Chromosome, telomere. Cell projection, axon. Cell projection, growth cone.
Protein Families
DNA2/NAM7 helicase family
Tissue Specificity
Highly expressed in skeletal muscle. Expressed in heart, fibroblast, placenta and liver. Weakly expressed in brain and lung. Expressed in the cortex of the kidney (highly expressed in tubular epithelial cells but low expression in the glomerulus).
