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Showing SETX — SEN1 is a alias.

SETX

Helicase senataxin · UniProt Q7Z333

Length
2677 aa
Mass
302.9 kDa
Annotated
2026-06-10
59 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Senataxin (SETX) is an SF1B-family RNA/DNA helicase that resolves R-loops (RNA:DNA hybrids) to protect the genome from transcription-associated replication stress and to couple transcription termination with RNA surveillance (PMID:37832548, PMID:24637776, PMID:39389664). Structural work on the yeast ortholog Sen1 establishes an elongated, inchworm-like enzyme with an N-terminal helical-repeat domain that autoinhibits by occluding the substrate cleft and a C-terminal motor core that encircles single-stranded RNA and translocates via a single-nucleotide power stroke; AOA2-associated RNA-binding mutations inactivate the helicase by disrupting this cleft (PMID:37832548). SETX is recruited to transcription pause and termination sites, where it cooperates with Xrn2 and the RNA exosome to drive RNAPII pausing and premature termination (PMID:22980978); its interaction with the exosome subunit Rrp45 is SUMO-dependent and is selectively abolished by AOA2 but not ALS4 mutations (PMID:24105744). R-loop unwinding by full-length SETX is directly stimulated by the BRCA1-BARD1 complex, which also relieves RAD52-mediated inhibition, and recruitment is promoted by Ser642 phosphorylation that engages the BRCA1 BRCT domains (PMID:41917467). Loss of SETX causes R-loop accumulation, transcription-replication conflicts, fork stalling and DNA breaks in a replication-dependent manner (PMID:24637776, PMID:41917467), leading to mitotic chromosome fragility resolved by FANCD2/XPF/MUS81-dependent mitotic DNA synthesis (PMID:36543851) and to break-induced replication driven by RAD52/XPF hyper-resection and PIF1/PCNA-ubiquitination (PMID:41037402); SETX is correspondingly synthetic lethal with FANCD2, PIF1, RAD52, and XPF (PMID:36543851, PMID:41037402). SETX is induced during hypoxia through the PERK/ATF4 arm of the unfolded protein response to suppress replication stress (PMID:34140498), directly drives transcription of autophagy genes (PMID:32686621), and supports class switch recombination to IgA through R-loop resolution at the switch region [PMID:bio_10.1101_2025.09.23.678005]. Missense mutations in the helicase domain cause ALS4, where mutant SETX produces motor neuron degeneration with TDP-43 mislocalization and nucleocytoplasmic transport defects (PMID:15106121, PMID:29725819).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2004 Medium

    Established SETX as a disease gene and predicted its biochemical identity, framing helicase activity or RNA processing as central to motor neuron survival.

    Evidence Mutation analysis within the ALS4 interval plus sequence-homology domain identification (to RENT1/IGHMBP2)

    PMID:15106121

    Open questions at the time
    • No in vitro helicase activity demonstrated
    • Substrate of the predicted helicase not identified
    • Mechanism linking mutation to neuronal loss unresolved
  2. 2012 High

    Placed SETX in a transcription-termination pathway by showing it drives RNAPII pausing and premature termination in cooperation with Xrn2 and the exosome.

    Evidence ChIP, ChIP-seq, and transcription termination assays at the HIV-1 promoter in cells

    PMID:22980978

    Open questions at the time
    • Did not establish direct biochemical activity on R-loops
    • Recruitment mechanism to cellular gene targets incompletely defined
  3. 2013 High

    Defined how SETX physically engages the RNA exosome and discriminated two disease mechanisms by showing SUMO-dependent Rrp45 binding is lost in AOA2 but not ALS4 alleles.

    Evidence Co-IP, in-cell sumoylation assays, immunofluorescence co-localization, and disease-allele comparison; complemented by yeast two-hybrid identification of self-association and ubiquitin/SUMO modification

    PMID:24105744 PMID:24244371

    Open questions at the time
    • SUMO E3 ligase and acceptor sites not mapped
    • Functional consequence of self-association unclear
    • BCYRN1-antisense interaction of L389S mutant of uncertain significance
  4. 2014 Medium

    Demonstrated SETX resolves R-loops in a replication-dependent manner and dissociated this activity from the AOA2 brain neurodegeneration phenotype.

    Evidence DRIP across mouse tissues and cultured cells with Setx knockdown/knockout

    PMID:24637776

    Open questions at the time
    • Did not explain the non-replicative basis of brain neurodegeneration
    • Direct enzymatic unwinding not shown in this study
  5. 2018 High

    Connected ALS4 SETX mutations to a neurodegenerative mechanism shared with broader ALS pathology, namely TDP-43 mislocalization and impaired nucleocytoplasmic transport.

    Evidence Transgenic and knock-in mouse models, neuropathology, nuclear import assays, and postmortem ALS4 patient tissue

    PMID:29725819

    Open questions at the time
    • Molecular link between helicase dysfunction and transport defect unresolved
    • Whether R-loops drive the neuronal phenotype not established
  6. 2020 High

    Revealed a transcriptional role for SETX in proteostasis by showing it directly regulates autophagy gene expression.

    Evidence siRNA knockdown, RNA-seq, autophagy flux assays, ChIP at autophagy genes, and AOA2 patient fibroblasts

    PMID:32686621

    Open questions at the time
    • Mechanism by which SETX promotes autophagy gene transcription not detailed
    • Relationship to its R-loop function unclear
  7. 2021 High

    Identified an inducible stress pathway controlling SETX, showing PERK/ATF4-driven SETX induction protects replication during hypoxia.

    Evidence Hypoxic knockdown, DRIP, DNA fiber assays, and PERK/ATF4 genetic epistasis

    PMID:34140498

    Open questions at the time
    • Direct ATF4 regulation of the SETX promoter not mapped
    • Generality beyond hypoxic stress untested
  8. 2022 High

    Showed unresolved SETX R-loops persist into mitosis and are rescued by a FANCD2/XPF/MUS81 mitotic DNA synthesis pathway, defining a synthetic-lethal vulnerability.

    Evidence SETX/FANCD2 co-depletion, DNA fiber and MiDAS assays, chromosome fragility, XPF/MUS81 inhibition, and viability assays

    PMID:36543851

    Open questions at the time
    • Recruitment of FANCD2 to SETX-dependent sites mechanistically undefined
    • Cancer-context specificity of synthetic lethality not delineated
  9. 2023 High

    Resolved the structural basis of SETX catalysis, defining N-terminal autoinhibition, an RNA-encircling motor, and a single-nucleotide power stroke, and mapped AOA2 mutations to the substrate cleft.

    Evidence Cryo-EM and X-ray crystallography of yeast Sen1 with RNA and ADP-SO4, mutagenesis, and helicase assays

    PMID:37832548

    Open questions at the time
    • Structures are of the yeast ortholog, not human SETX
    • How autoinhibition is relieved in vivo not shown
    • R-loop (vs ssRNA) engagement structurally inferred
  10. 2023 Medium

    Linked SETX to repeat-expansion neurodegeneration, showing it suppresses arginine-DPR toxicity and modulates nucleolar liquidity via partially RNA-dependent DPR interaction.

    Evidence Drosophila C9orf72 modifier screens, cell models, Co-IP, FRAP, and GR localization imaging

    PMID:37845749

    Open questions at the time
    • Direct vs RNA-bridged DPR interaction not fully separated
    • Relevance to human ALS not established
    • Mechanism of nucleolar liquidity change unclear
  11. 2024 Medium

    Provided direct biochemical confirmation that purified Sen1/SETX is an active RNA-DNA helicase.

    Evidence Recombinant Chaetomium thermophilum Sen1 expression, affinity purification, and in vitro RNA-DNA hybrid helicase assay

    PMID:39389664

    Open questions at the time
    • Ortholog enzyme, methods-focused report
    • Substrate specificity and regulation not characterized here
  12. 2025 High

    Defined how defective SETX channels R-loop-associated breaks into mutagenic break-induced replication via RAD52/XPF hyper-resection and PIF1/PCNA-ubiquitination, exposing further synthetic-lethal partners.

    Evidence SETX-deficient cells, BIR reporter, fiber assays, PCNA ubiquitination blots, and RAD52/XPF/PIF1 epistasis and synthetic lethality

    PMID:41037402

    Open questions at the time
    • Trigger converting deDSBs into BIR substrates incompletely defined
    • In vivo relevance to disease tissues untested
  13. 2025 Medium

    Extended SETX R-loop resolution to immune function, showing it is required for class switch recombination to IgA at the Salpha switch region.

    Evidence SETX-knockout mouse B cell stimulation, IgA ELISA after influenza, DRIP at the IgA locus, and repertoire sequencing (preprint)

    PMID:bio_10.1101_2025.09.23.678005

    Open questions at the time
    • Preprint, single lab
    • Direct recruitment to the switch region not shown
    • Specificity for IgA vs other isotypes not fully resolved
  14. 2025 Medium

    Confirmed the ALS4 L389S allele acts through a gain-of-function/altered-activity mechanism reducing R-loop levels, and demonstrated allele-selective correction.

    Evidence Allele-specific siRNA in patient fibroblasts with immunoblot and DRIP rescue

    PMID:40200577

    Open questions at the time
    • Mechanism producing reduced R-loops by L389S not fully defined
    • Therapeutic durability in neurons untested
  15. 2026 High

    Reconstituted regulated R-loop unwinding by full-length human SETX, identifying BRCA1-BARD1 as a direct stimulatory partner and Ser642 phosphorylation as the BRCT-dependent recruitment signal.

    Evidence In vitro reconstitution with purified proteins, Co-IP, phospho-Ser642 and catalytic mutants, BRCT mapping, DRIP-seq, fiber assays, and gammaH2AX imaging

    PMID:41917467

    Open questions at the time
    • Kinase phosphorylating Ser642 not identified
    • Interplay between BRCA1-BARD1 stimulation and exosome/Xrn2 cooperation unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SETX's catalytic R-loop resolution mechanistically connects to the neuronal phenotypes (TDP-43 mislocalization, transport defects, DPR toxicity) and how the same enzyme is selectively deployed across replication, transcription termination, immune recombination, and autophagy regulation remain unresolved.
  • No human full-length structure bound to an R-loop
  • Kinase and full recruitment code for SETX at distinct genomic sites unknown
  • Causal chain from helicase loss to motor neuron death not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 3 GO:0003723 RNA binding 2 GO:0016787 hydrolase activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 1
Pathway
R-HSA-69306 DNA Replication 3 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-8953897 Cellular responses to stimuli 1 R-HSA-9612973 Autophagy 1
Partners
BARD1BRCA1FANCD2PIF1RAD52RRP45XPFXRN2

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 SETX encodes a 302.8-kDa protein containing a DNA/RNA helicase domain with strong homology to human RENT1 and IGHMBP2, proteins known to have roles in RNA processing; missense mutations (T3I, L389S, R2136H) in the helicase domain cause ALS4, implicating helicase activity or RNA processing in neuronal survival. Mutation analysis (sequencing) of candidate genes within the ALS4 interval on chromosome 9q34; domain homology analysis American journal of human genetics Medium 15106121
2012 SETX (Setx) is recruited to the HIV-1 promoter by Microprocessor (Drosha/Dgcr8) and cooperates with Xrn2 and Rrp6 to induce RNAPII pausing and premature transcription termination; ChIP-seq identified cellular gene targets whose transcription is modulated by this mechanism. Chromatin immunoprecipitation (ChIP), ChIP-seq, functional transcription termination assays, recruitment assays at the HIV-1 promoter Cell High 22980978
2013 SETX is sumoylated, and this SUMO modification enables its interaction with Rrp45, a core subunit of the RNA exosome; this SUMO-dependent interaction is disrupted by AOA2-associated SETX mutations but not ALS4 mutations, and SETX/Rrp45 co-localize in nuclear foci at sites of transcription-induced DNA damage. Co-immunoprecipitation (Co-IP) of SETX and Rrp45, SUMO modification assays, immunofluorescence co-localization, mutation analysis of AOA2 vs ALS4 alleles Genes & development High 24105744
2013 SETX self-associates via its amino-terminal protein-interaction domain; the ALS4 L389S mutant retains this self-association. SETX is modified by ubiquitin and SUMO monomers (post-translational modification confirmed by detection). The L389S mutant acquires an aberrant interaction with a peptide encoded by the antisense sequence of the brain-specific non-coding RNA BCYRN1, as identified by yeast two-hybrid screening. Yeast two-hybrid screen with human brain library, Co-IP to confirm self-association and dimerization, western blot detection of ubiquitin/SUMO modifications PloS one Medium 24244371
2014 SETX depletion leads to accumulation of R-loops (DNA:RNA hybrids) in proliferating cells (testes and cultured cells with active replication), enhanced by DNA damage; however, no R-loop accumulation was detected in brain tissue of Setx-knockout mice, indicating R-loop resolution by SETX is replication-dependent and does not contribute to the neurodegeneration phenotype in AOA2 brain. DRIP (DNA:RNA immunoprecipitation) in mouse tissues and cultured cells; Setx knockdown/knockout models; quantification of R-loops and DNA double-strand breaks PloS one Medium 24637776
2018 ALS4 SETX mutations (R2136H and L389S) expressed in mice cause motor neuron degeneration with TDP-43 nuclear clearing and cytosolic mislocalization, enhanced stress granule formation, and nuclear membrane abnormalities (Ran/RanGAP1 mis-localization); nuclear import was delayed in ALS4 cortical neurons, linking SETX dysfunction to impaired nucleocytoplasmic trafficking common to ALS pathology. Transgenic and knock-in mouse models; neuropathological immunostaining (TDP-43, Ran, RanGAP1, stress granule markers); nucleocytoplasmic transport assays; postmortem ALS4 patient spinal cord analysis Acta neuropathologica High 29725819
2020 SETX depletion inhibits autophagy progression, leading to accumulation of ubiquitinated proteins, impaired clearance of protein aggregates, and mitochondrial defects; SETX directly regulates transcription of autophagy genes (including ATG7, ULK1, BECN1 pathway members). AOA2 patient fibroblasts also show perturbation of the autophagy pathway. SETX siRNA knockdown; transcriptomic analysis (RNA-seq); autophagy flux assays (LC3 puncta, p62/SQSTM1 accumulation, bafilomycin/chloroquine treatment); ChIP for autophagy gene transcription; mitochondrial imaging; AOA2 patient fibroblast analysis Autophagy High 32686621
2021 In hypoxia, R-loops accumulate and SETX expression is induced via the PERK/ATF4 arm of the unfolded protein response (UPR); loss of hypoxia-induced SETX results in increased R-loop levels, DNA damage accumulation, and decreased DNA replication rates, linking SETX to protection from transcription-associated replication stress during hypoxia. SETX knockdown under hypoxic conditions; DRIP assay for R-loop quantification; DNA damage markers (γH2AX); DNA fiber assays for replication rate; UPR pathway inhibition and activation (PERK inhibitor, ATF4 knockdown); immunoblotting Nature communications High 34140498
2022 Loss of SETX causes spontaneous under-replication and chromosome fragility due to transcription-associated R-loops persisting into mitosis; FANCD2 is recruited to these fragile sites to facilitate mitotic DNA synthesis dependent on XPF and MUS81 endonucleases, preventing chromosome mis-segregation. Co-depletion of FANCD2 and SETX is synthetic lethal in cancer cells. SETX and FANCD2 siRNA co-depletion; DNA fiber assays; chromosome fragility analysis; immunofluorescence for FANCD2 foci; mitotic DNA synthesis assays; XPF/MUS81 inhibition; cell viability/proliferation assays Communications biology High 36543851
2023 Cryo-EM and X-ray crystal structures of yeast Sen1 (SETX ortholog) reveal an elongated inchworm-like architecture with an N-terminal helical repeat (Sen1N) regulatory domain flexibly linked to a C-terminal SF1B helicase motor core. Sen1N promotes autoinhibition by occluding the RNA substrate-binding cleft. The crystal structure of activated Sen1Hel bound to single-stranded RNA and ADP-SO4 shows the enzyme encircles RNA, implicating a single-nucleotide power stroke in RNA translocation. AOA2-associated RNA-binding-deficient SETX mutations inactivate helicase activity by disrupting the substrate-binding cleft. Cryo-EM structure determination; X-ray crystallography of helicase domain with RNA and ADP-SO4; mutagenesis of RNA-binding interface; helicase activity assays; structural mapping of AOA2 mutations Molecular cell High 37832548
2023 Reduced SETX expression enhances arginine-containing dipeptide repeat (DPR) toxicity and C9orf72 repeat expansion toxicity; SETX co-expression dramatically suppresses disease phenotypes in Drosophila (G4C2)58 and GR(50) models, and causes relocalization of GR(50) out of the nucleolus. SETX physically interacts with arginine-containing DPRs in a partially RNA-dependent manner and modulates nucleolus liquidity. SETX overexpression/knockdown in HEK293 cells and primary neurons; Drosophila genetic modifier screens with (G4C2)58, GR(50), and GR(1000) models; co-immunoprecipitation of SETX and DPRs; FRAP for nucleolus liquidity; immunofluorescence for GR localization Acta neuropathologica communications Medium 37845749
2025 When SETX is defective, R-loop/hybrid-accumulated double-ended DSBs (deDSBs) trigger hyper-recombination via break-induced replication (BIR); SETX loss induces non-canonical hyper-end resection requiring RAD52 and XPF, and stalls Polα-primase-initiated end-fill synthesis due to RNA/DNA hybrid accumulation on ssDNA overhangs, leading to PCNA ubiquitination and PIF1 loading that initiates BIR. SETX is synthetic lethal with PIF1, RAD52, or XPF. SETX-deficient cell lines; BIR reporter assays; DNA fiber assays; PCNA ubiquitination western blot; RAD52, XPF, PIF1 co-depletion epistasis experiments; synthetic lethality assays Cell reports High 41037402
2026 Full-length SETX unwinds R-loops with broad specificity in vitro; the BRCA1-BARD1 complex binds R-loops and directly stimulates R-loop unwinding by SETX; BRCA1-BARD1 alleviates inhibition of SETX by RAD52. Phosphorylation of Ser642 in SETX promotes its interaction with BRCA1 via the tandem BRCT domain of BRCA1. Mutations in the SETX catalytic domain or at Ser642 cause R-loop accumulation, transcription-replication conflicts, replication fork stalling, and DNA double-strand breaks in human cells. In vitro R-loop unwinding reconstitution assay with purified proteins; Co-IP of SETX and BRCA1-BARD1; phospho-Ser642 mutant analysis; BRCT domain interaction mapping; DRIP-seq for R-loop quantification in cells; DNA fiber assay for replication fork stalling; γH2AX immunofluorescence Nature structural & molecular biology High 41917467
2025 Allele-specific siRNA targeting the ALS4 c.1166T>C (L389S) mutant SETX transcript selectively reduces mutant SETX protein while sparing wild-type, and restores R-loop levels in ALS4 patient fibroblasts, confirming that the L389S ALS4 mutation results in reduced R-loop levels (a loss-of-R-loop-resolution phenotype). Allele-specific siRNA transfection in HEK293 cells and ALS4 primary fibroblasts; immunoblot for mutant vs wild-type SETX protein; DRIP assay for R-loop quantification HGG advances Medium 40200577
2024 Recombinant Sen1 (SETX ortholog from Chaetomium thermophilum) expressed in mammalian cells and purified via YFP-nanobody affinity support displays quantifiable RNA-DNA duplex resolution (helicase) activity in biochemical assays, confirming SETX/Sen1 is an active RNA-DNA helicase enzyme. Recombinant protein expression in mammalian cells; YFP-nanobody affinity purification; in vitro RNA-DNA hybrid helicase activity assay Methods in enzymology Medium 39389664
2025 In SETX-knockout mice, ex vivo polyclonal stimulation of B cells yields significantly fewer IgA-producing cells compared to wild-type; SETX-knockout mice generate reduced antigen-specific IgA titers following influenza A infection; SETX-deficient mice show increased R-loop formation within the IgA locus, establishing a role for SETX in class switch recombination to IgA through R-loop resolution at the Sα switch region. SETX-knockout mouse B cell stimulation assays; ELISA for IgA titers post-influenza infection; DRIP assay for R-loops at the IgA locus; B cell repertoire sequencing bioRxivpreprint Medium bio_10.1101_2025.09.23.678005
2017 Expression of an AOA2-causative truncated form of human SETX in Drosophila muscles alters translational repression of the RNA-binding protein Elav (normally repressed outside neurons), indicating that mutant SETX disrupts RNA-specific translational regulatory mechanisms. Transgenic Drosophila expressing truncated human SETX; immunostaining and western blot for Elav protein in muscle vs neuronal tissues; NMJ morphology analysis Synapse (New York, N.Y.) Low 28245518

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). American journal of human genetics 642 15106121
2012 Microprocessor, Setx, Xrn2, and Rrp6 co-operate to induce premature termination of transcription by RNAPII. Cell 150 22980978
2013 A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the neurodegenerative disease AOA2, targets the exosome to sites of transcription-induced DNA damage. Genes & development 102 24105744
1998 Identification of Candida albicans ALS2 and ALS4 and localization of als proteins to the fungal cell surface. Journal of bacteriology 85 9765564
2023 Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4. PLoS pathogens 63 36913408
2014 R-loops in proliferating cells but not in the brain: implications for AOA2 and other autosomal recessive ataxias. PloS one 53 24637776
2020 SETX (senataxin), the helicase mutated in AOA2 and ALS4, functions in autophagy regulation. Autophagy 50 32686621
2018 Senataxin mutations elicit motor neuron degeneration phenotypes and yield TDP-43 mislocalization in ALS4 mice and human patients. Acta neuropathologica 49 29725819
2006 Autosomal recessive ataxia with peripheral neuropathy and elevated AFP: novel mutations in SETX. Neurology 43 16717225
2021 Hypoxia-induced SETX links replication stress with the unfolded protein response. Nature communications 35 34140498
2000 A gene for autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4) localizes to a 500-kb interval on chromosome 9q34. Neurogenetics 32 11085590
2011 SETX gene mutation in a family diagnosed autosomal dominant proximal spinal muscular atrophy. Neuromuscular disorders : NMD 31 22088787
2013 SETX mutations are a frequent genetic cause of juvenile and adult onset cerebellar ataxia with neuropathy and elevated serum alpha-fetoprotein. Orphanet journal of rare diseases 30 23941260
2008 "Pseudodominant inheritance" of ataxia with ocular apraxia type 2 (AOA2). Journal of neurology 30 18350359
2012 The SETX missense variation spectrum as evaluated in patients with ALS4-like motor neuron diseases. Neurogenetics 24 23129421
2009 Characterization of two novel SETX mutations in AOA2 patients reveals aspects of the pathophysiological role of senataxin. Neurogenetics 24 19593598
2019 Disruption of Spermatogenesis and Infertility in Ataxia with Oculomotor Apraxia Type 2 (AOA2). Cerebellum (London, England) 23 30778901
2017 High-throughput sequencing revealed a novel SETX mutation in a Hungarian patient with amyotrophic lateral sclerosis. Brain and behavior 23 28413711
2022 FANCD2 promotes mitotic rescue from transcription-mediated replication stress in SETX-deficient cancer cells. Communications biology 21 36543851
2013 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. PloS one 19 24244371
2011 A monoclonal antibody specific for Candida albicans Als4 demonstrates overlapping localization of Als family proteins on the fungal cell surface and highlights differences between Als localization in vitro and in vivo. FEMS immunology and medical microbiology 19 22106872
2008 Identification and characterisation of a large senataxin (SETX) gene duplication in ataxia with ocular apraxia type 2 (AOA2). Neurogenetics 19 18663494
2018 A novel SETX gene mutation associated with Juvenile amyotrophic lateral sclerosis. Brain and behavior 13 30052327
2023 Sen1 architecture: RNA-DNA hybrid resolution, autoregulation, and insights into SETX inactivation in AOA2. Molecular cell 12 37832548
2015 An atypical form of AOA2 with myoclonus associated with mutations in SETX and AFG3L2. BMC medical genetics 12 25927548
2021 De novo pathogenic variant in SETX causes a rapidly progressive neurodegenerative disorder of early childhood-onset with severe axonal polyneuropathy. Acta neuropathologica communications 11 34922620
2013 Novel mutations in ataxia telangiectasia and AOA2 associated with prolonged survival. Journal of the neurological sciences 11 24090759
2021 AOA-2 Derivatives as Outer Membrane Protein A Inhibitors for Treatment of Gram-Negative Bacilli Infections. Frontiers in microbiology 10 33643267
2014 SETX sumoylation: A link between DNA damage and RNA surveillance disrupted in AOA2. Rare diseases (Austin, Tex.) 10 25054092
2013 Novel SETX variants in a patient with ataxia, neuropathy, and oculomotor apraxia are associated with normal sensitivity to oxidative DNA damaging agents. Brain & development 9 24183476
2018 A Novel Homozygous Variant of SETX Causes Ataxia with Oculomotor Apraxia Type 2. Journal of clinical neurology (Seoul, Korea) 8 30198223
2012 Clinical and molecular findings of ataxia with oculomotor apraxia type 2 (AOA2) in 5 Tunisian families. Diagnostic molecular pathology : the American journal of surgical pathology, part B 8 23111195
2009 A novel nonsense mutation in a Japanese family with ataxia with oculomotor apraxia type 2 (AOA2). Journal of human genetics 8 19893583
2023 Senataxin helicase, the causal gene defect in ALS4, is a significant modifier of C9orf72 ALS G4C2 and arginine-containing dipeptide repeat toxicity. Acta neuropathologica communications 7 37845749
2013 A new SETX mutation producing AOA2 in two siblings. The International journal of neuroscience 7 23566282
2018 Ataxia with ocular apraxia type 2 not responding to 4-aminopyridine: A rare mutation in the SETX gene in a Saudi patient. Intractable & rare diseases research 6 30560021
2022 A Novel SETX Mutation in a Taiwanese Patient with Autosomal Recessive Cerebellar Ataxia Detected by Targeted Next-Generation Sequencing, and a Literature Review. Brain sciences 5 35203940
2022 A Patient with Corticobasal Syndrome and Progressive Non-Fluent Aphasia (CBS-PNFA), with Variants in ATP7B, SETX, SORL1, and FOXP1 Genes. Genes 5 36553628
2025 Break-induced replication is activated to repair R-loop-associated double-strand breaks in SETX-deficient cells. Cell reports 4 41037402
2020 Unusual electrophysiological findings in a Chinese ALS 4 family with SETX-L389S mutation: a three-year follow-up. Journal of neurology 4 32997296
2017 Altered translational repression of an RNA-binding protein, Elav by AOA2-causative Senataxin mutation. Synapse (New York, N.Y.) 4 28245518
2022 Unique Ataxia-Oculomotor Apraxia 2 (AOA2) in Israel with Novel Variants, Atypical Late Presentation, and Possible Identification of a Poison Exon. Journal of molecular neuroscience : MN 3 35676594
2022 Ataxia with oculomotor apraxia type 2 caused by a novel homozygous mutation in SETX gene, and literature review. Frontiers in molecular neuroscience 3 36438189
2018 [Screening of the SETX gene in sporadic amyotrophic lateral sclerosis patients of Chinese origin]. Zhonghua yi xue za zhi 3 30220148
2024 A novel mutation in SETX and ATM causes ataxia in consanguineous Pakistani families. Pakistan journal of medical sciences 2 39281240
2021 Heterozygous deletion in exon 6 of STEX gene causing ataxia with oculomotor apraxia type 2 (AOA-2) with ovarian failure. BMJ case reports 2 34193451
2026 Resolution of R-loops and transcription-replication conflicts by SETX-BRCA1-BARD1 complex. Nature structural & molecular biology 1 41917467
2025 Allele-specific silencing of a dominant SETX mutation in familial amyotrophic lateral sclerosis type 4. HGG advances 1 40200577
2025 Break-induced replication is activated to repair R-loop-associated double-strand breaks in SETX-deficient cells. bioRxiv : the preprint server for biology 1 40475435
2020 Biallelic Mutation of SETX and Additional Likely "In Cis" SETX Sequence Change in Ataxia with Oculomotor Apraxia Type 2. Journal of pediatric genetics 1 34849277
2026 Progressive abnormal gait in an adult Jack Russell Terrier with a homozygous frameshift variant in SETX (senataxin). Journal of veterinary internal medicine 0 42105303
2025 Unveiling ten novel SETX mutations: implications for ALS pathogenesis and clinical diversity. Somatosensory & motor research 0 40338003
2025 A Very Rare Setx Gene Variant (C.2750T>C) In a 72-year-old Man with Amyotrophic Lateral Sclerosis and an Unremarkable Family History. Should Genetic Testing be Routinely Performed in all Patients? European journal of case reports in internal medicine 0 41064708
2024 Obsessive-compulsive disorder as a first manifestation of Ataxia with Oculomotor Apraxia type 2 due to a novel mutation of SETX gene. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 0 39294407
2024 Expression, purification, and biochemical analysis of the RNA-DNA hybrid helicase Sen1/SETX from Chaetomium thermophilum. Methods in enzymology 0 39389664
2024 Allele-specific silencing of a dominant SETX mutation in familial amyotrophic lateral sclerosis type 4. bioRxiv : the preprint server for biology 0 39416141
2023 Genetic heterogeneity within a consanguineous family involving TTPA and SETX genes. Journal of neurogenetics 0 38109176
2022 [A case of sporadic amyotrophic lateral sclerosis (ALS) with Senataxin (SETX) gene variant]. Rinsho shinkeigaku = Clinical neurology 0 35228463
2020 Some pathogenic SETX variants are partially conserved during evolution. Gene 0 33333218

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