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SETX senataxin [ Homo sapiens (human) ]

Gene ID: 23064, updated on 2-Mar-2021

Summary

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Official Symbol
SETXprovided by HGNC
Official Full Name
senataxinprovided by HGNC
Primary source
HGNC:HGNC:445
See related
Ensembl:ENSG00000107290 MIM:608465
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ALS4; AOA2; Sen1; SCAN2; SCAR1; bA479K20.2
Summary
This gene encodes a protein named for its homology to the Sen1p protein of fungi which has RNA helicase activity encoded by a domain at the C-terminal end of the protein. The protein encoded by this gene contains a DNA/RNA helicase domain at its C-terminal end which suggests that it may be involved in both DNA and RNA processing. Mutations in this gene have been associated with ataxia-ocular apraxia-2 (AOA2) and an autosomal dominant form of juvenile amyotrophic lateral sclerosis (ALS4). [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in thyroid (RPKM 20.6), testis (RPKM 18.7) and 24 other tissues See more
Orthologs
mouse all
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Genomic context

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See SETX in Genome Data Viewer
Location:
9q34.13
Exon count:
33
Annotation release Status Assembly Chr Location
109.20210226 current GRCh38.p13 (GCF_000001405.39) 9 NC_000009.12 (132261356..132356726, complement)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (135136743..135230373, complement)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376302 Neighboring gene netrin G2 Neighboring gene Sharpr-MPRA regulatory region 6614 Neighboring gene transcription termination factor 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Some pathogenic SETX variants are partially conserved during evolution. Tariq H, et al. Gene, 2021 Mar 1. PMID 33333218
  2. Clinical and Molecular Aspects of Senataxin Mutations in Amyotrophic Lateral Sclerosis 4. Grunseich C, et al. Ann Neurol, 2020 Apr. PMID 31957062, Free PMC Article
  3. [Screening of the SETX gene in sporadic amyotrophic lateral sclerosis patients of Chinese origin]. Zhang H, et al. Zhonghua Yi Xue Za Zhi, 2018 Sep 4. PMID 30220148
  4. A novel SETX gene mutation associated with Juvenile amyotrophic lateral sclerosis. Ma L, et al. Brain Behav, 2018 Sep. PMID 30052327, Free PMC Article
  5. Senataxin resolves RNA:DNA hybrids forming at DNA double-strand breaks to prevent translocations. Cohen S, et al. Nat Commun, 2018 Feb 7. PMID 29416069, Free PMC Article

See all (98) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Clinical and genetic findings in a cohort of Chinese patients with autosomal recessive spinocerebellar ataxia.
    Title: Clinical and genetic findings in a cohort of Chinese patients with autosomal recessive spinocerebellar ataxia.
  2. Some pathogenic SETX variants are partially conserved during evolution.
    Title: Some pathogenic SETX variants are partially conserved during evolution.
  3. A cellular assay for SETX function confirmed that like the Leu389Ser mutation, the Glu385Lys variant leads to a decrease in R loops, likely from a gain of function. The molecular characterization of R-loop levels in patient-derived cells provides insight into ALS4 pathology.
    Title: Clinical and Molecular Aspects of Senataxin Mutations in Amyotrophic Lateral Sclerosis 4.
  4. Mutations in senataxin (SETX) gene have been described as a rare underlying cause of autosomal dominant form of juvenile-onset familial amyotrophic lateral sclerosis.
    Title: A novel SETX gene mutation associated with Juvenile amyotrophic lateral sclerosis.
  5. Senataxin (SETX)-deficiency results in increased RNA-DNA hybrids (R-loops) and DNA double-strand breaks (DSBs), and deficiency of DNA-activated protein kinase-catalytic subunit (DNA-PKcs), which impairs DSB repair. SETX overexpression in SMA neurons reduces R-loops and DNA damage, and rescues neurodegeneration.
    Title: Combined deficiency of Senataxin and DNA-PKcs causes DNA damage accumulation and neurodegeneration in spinal muscular atrophy.
  6. Overexpression of the RNA-DNA helicase Senataxin suppresses DNA damage sensitivity and R-loop accumulation in Sae2/CtIP-deficient cells, and a catalytic mutant of CtIP fails to complement this sensitivity, indicating a role for CtIP nuclease activity in the repair process.
    Title: Sae2/CtIP prevents R-loop accumulation in eukaryotic cells.
  7. Mutation in SETX associated with ALS4 reduces formation of R-loops (three-stranded nucleic acid structures) which results in increased global DNA methylation and reduced transcription of the BAMBI gene, a negative regulator of TGFbeta signaling
    Title: Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters.
  8. Patients carried SETX mutations were not different from other patients in onset age
    Title: [Screening of the SETX gene in sporadic amyotrophic lateral sclerosis patients of Chinese origin].
  9. Study report a previously uncharacterized protein, SAN1, the Fam120b gene product, as a 5' exonuclease that acts independently of the Fanconi anemia pathway in response to inter-strand DNA cross-links (ICLs). Deletion of SAN1 in HeLa cells and mouse embryonic fibroblasts causes sensitivity to ICLs. SAN1 binds to senataxin (SETX). SAN1-SETX binding is increased by ICLs and is required to prevent cross-link sensitivity.
    Title: A senataxin-associated exonuclease SAN1 is required for resistance to DNA interstrand cross-links.
  10. Data suggest that senataxin (SETX) functions at DNA double-strand breaks (DSBs) in order to limit translocations and ensure cell viability.
    Title: Senataxin resolves RNA:DNA hybrids forming at DNA double-strand breaks to prevent translocations.
Submit: New GeneRIF Correction See all GeneRIFs (52)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ12840, FLJ43459, KIAA0625, DKFZp781B151

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
  
DNA binding IC
Inferred by Curator
more info
 PubMed 
DNA helicase activity TAS
Traceable Author Statement
more info
 PubMed 
RNA binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
transcription termination site sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
transcription termination site sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
DNA duplex unwinding IEA
Inferred from Electronic Annotation
more info
  
DNA recombination IEA
Inferred from Electronic Annotation
more info
  
DNA-templated transcription, termination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
MAPK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
RNA processing TAS
Traceable Author Statement
more info
 PubMed 
cell differentiation IEA
Inferred from Electronic Annotation
more info
  
cellular response to DNA damage stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
cellular response to fibroblast growth factor stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
cellular response to hydrogen peroxide IDA
Inferred from Direct Assay
more info
 PubMed 
cellular response to oxidative stress IDA
Inferred from Direct Assay
more info
 PubMed 
cellular response to retinoic acid IDA
Inferred from Direct Assay
more info
 PubMed 
circadian rhythm IEA
Inferred from Electronic Annotation
more info
  
double-strand break repair IDA
Inferred from Direct Assay
more info
 PubMed 
fibroblast growth factor receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
mRNA splice site selection IMP
Inferred from Mutant Phenotype
more info
 PubMed 
negative regulation of apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
nervous system development IEA
Inferred from Electronic Annotation
more info
  
positive regulation of DNA-templated transcription, initiation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
positive regulation of DNA-templated transcription, termination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
positive regulation of RNA splicing IMP
Inferred from Mutant Phenotype
more info
 PubMed 
positive regulation of neuron projection development IDA
Inferred from Direct Assay
more info
 PubMed 
positive regulation of termination of RNA polymerase II transcription, poly(A)-coupled IMP
Inferred from Mutant Phenotype
more info
 PubMed 
positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
 PubMed 
protein kinase B signaling IDA
Inferred from Direct Assay
more info
 PubMed 
spermatogenesis IEA
Inferred from Electronic Annotation
more info
  
termination of RNA polymerase II transcription IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
Component Evidence Code Pubs
axon IDA
Inferred from Direct Assay
more info
 PubMed 
chromosome, telomeric region IEA
Inferred from Electronic Annotation
more info
  
cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
growth cone IDA
Inferred from Direct Assay
more info
 PubMed 
intercellular bridge IDA
Inferred from Direct Assay
more info
  
nuclear body IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
nuclear body IDA
Inferred from Direct Assay
more info
  
nuclear chromosome IDA
Inferred from Direct Assay
more info
 PubMed 
nucleolus IEA
Inferred from Electronic Annotation
more info
  
nucleoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
probable helicase senataxin
Names
SEN1 homolog
amyotrophic lateral sclerosis 4 protein
NP_001338456.1
NP_001338457.1
NP_055861.3
XP_005272229.1
XP_005272230.1
XP_011516706.1
XP_011516707.1
XP_011516708.1
XP_011516709.1
XP_011516710.1
XP_016869985.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_007946.1 RefSeqGene

    Range
    5001..98546
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_268

mRNA and Protein(s)

  1. NM_001351527.2 → NP_001338456.1  probable helicase senataxin isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    AA609547, AB014525, AI123313, AL353701, AY362728, BX538166, DA794966, DA989674
    Consensus CDS
    CCDS6947.1
    Conserved Domains (3) summary
    pfam12726
    Location:37 → 351
    SEN1_N; SEN1 N terminal
    pfam13086
    Location:1933 → 2218
    AAA_11; AAA domain
    pfam13087
    Location:2225 → 2424
    AAA_12; AAA domain

  2. NM_001351528.2 → NP_001338457.1  probable helicase senataxin isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate in-frame exon in the 3' coding region, compared to variant 1. The encoded isoform (2) has the same N- and C-terimini, but is longer than isoform 1.
    Source sequence(s)
    AA609547, AB014525, AI123313, AK302394, AY362728, BX538166, DA989674
    Conserved Domains (3) summary
    pfam12726
    Location:37 → 351
    SEN1_N; SEN1 N terminal
    pfam13086
    Location:1933 → 2218
    AAA_11; AAA domain
    pfam13087
    Location:2225 → 2424
    AAA_12; AAA domain

  3. NM_015046.7 → NP_055861.3  probable helicase senataxin isoform 1

    See identical proteins and their annotated locations for NP_055861.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the shortest transcript and encodes the shorter isoform (1). Variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    AA609547, AB014525, AI123313, AY362728, BX538166, DA989674
    Consensus CDS
    CCDS6947.1
    UniProtKB/Swiss-Prot
    Q7Z333
    Related
    ENSP00000224140.5, ENST00000224140.6
    Conserved Domains (3) summary
    pfam12726
    Location:37 → 351
    SEN1_N; SEN1 N terminal
    pfam13086
    Location:1933 → 2218
    AAA_11; AAA domain
    pfam13087
    Location:2225 → 2424
    AAA_12; AAA domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210226

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000009.12 Reference GRCh38.p13 Primary Assembly

    Range
    132261356..132356726 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017014496.1 → XP_016869985.1  probable helicase senataxin isoform X5

    Related
    ENSP00000409143.1, ENST00000436441.5

  2. XM_005272172.3 → XP_005272229.1  probable helicase senataxin isoform X1

    See identical proteins and their annotated locations for XP_005272229.1

    UniProtKB/Swiss-Prot
    Q7Z333
    Conserved Domains (3) summary
    pfam12726
    Location:37 → 351
    SEN1_N; SEN1 N terminal
    pfam13086
    Location:1933 → 2218
    AAA_11; AAA domain
    pfam13087
    Location:2225 → 2424
    AAA_12; AAA domain

  3. XM_011518404.3 → XP_011516706.1  probable helicase senataxin isoform X1

    See identical proteins and their annotated locations for XP_011516706.1

    UniProtKB/Swiss-Prot
    Q7Z333
    Conserved Domains (3) summary
    pfam12726
    Location:37 → 351
    SEN1_N; SEN1 N terminal
    pfam13086
    Location:1933 → 2218
    AAA_11; AAA domain
    pfam13087
    Location:2225 → 2424
    AAA_12; AAA domain

  4. XM_011518405.3 → XP_011516707.1  probable helicase senataxin isoform X1

    See identical proteins and their annotated locations for XP_011516707.1

    UniProtKB/Swiss-Prot
    Q7Z333
    Conserved Domains (3) summary
    pfam12726
    Location:37 → 351
    SEN1_N; SEN1 N terminal
    pfam13086
    Location:1933 → 2218
    AAA_11; AAA domain
    pfam13087
    Location:2225 → 2424
    AAA_12; AAA domain

  5. XM_005272173.3 → XP_005272230.1  probable helicase senataxin isoform X1

    See identical proteins and their annotated locations for XP_005272230.1

    UniProtKB/Swiss-Prot
    Q7Z333
    Conserved Domains (3) summary
    pfam12726
    Location:37 → 351
    SEN1_N; SEN1 N terminal
    pfam13086
    Location:1933 → 2218
    AAA_11; AAA domain
    pfam13087
    Location:2225 → 2424
    AAA_12; AAA domain

  6. XM_011518406.2 → XP_011516708.1  probable helicase senataxin isoform X2

    Conserved Domains (4) summary
    pfam12726
    Location:37 → 356
    SEN1_N; SEN1 N terminal
    pfam13086
    Location:1933 → 2218
    AAA_11; AAA domain
    pfam13087
    Location:2225 → 2400
    AAA_12; AAA domain
    pfam13245
    Location:1957 → 2020
    AAA_19; Part of AAA domain

  7. XM_011518407.1 → XP_011516709.1  probable helicase senataxin isoform X3

    Conserved Domains (4) summary
    pfam12726
    Location:37 → 356
    SEN1_N; SEN1 N terminal
    pfam13086
    Location:1933 → 2218
    AAA_11; AAA domain
    pfam13245
    Location:1957 → 2020
    AAA_19; Part of AAA domain
    cl22977
    Location:2225 → 2366
    UvrD_C_2; UvrD-like helicase C-terminal domain

  8. XM_011518408.3 → XP_011516710.1  probable helicase senataxin isoform X4

    Conserved Domains (3) summary
    pfam12726
    Location:37 → 356
    SEN1_N; SEN1 N terminal
    pfam13086
    Location:1933 → 2182
    AAA_11; AAA domain
    pfam13245
    Location:1957 → 2020
    AAA_19; Part of AAA domain

RNA

  1. XR_001746251.1 RNA Sequence

  2. XR_929739.2 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q7Z333.4 GenPept UniProtKB/Swiss-Prot:Q7Z333

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