SETX senataxin [Homo sapiens (human)] - Gene

Summary

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; 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

Genomic context

Location:: 9q34.13

Exon count:: 33

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	9	NC_000009.12 (132261356..132356726, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (135136827..135232113, complement)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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 Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

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.
Expression of AOA2-causative form of SETX in Drosophila muscles resulted in an alteration of translational repression of Elav.
Title: Altered translational repression of an RNA-binding protein, Elav by AOA2-causative Senataxin mutation.
The pan-neuronal expression of wild-type or mutant forms of human senataxin induced morphological plasticity at neuromuscular junction synapses.
Title: Human Senataxin Modulates Structural Plasticity of the Neuromuscular Junction in Drosophila through a Neuronally Conserved TGFβ Signalling Pathway.
Novel compound heterozygous mutations of SETX in Chinese AOA2 pedigree were identified, which broaden the mutation spectrum of SETX.
Title: Identification of novel senataxin mutations in Chinese patients with autosomal recessive cerebellar ataxias by targeted next-generation sequencing.
The role of senataxin in regulating gene expression on a genome-wide scale in Ataxia oculomotor apraxia 2 neurons is described.
Title: A new model to study neurodegeneration in ataxia oculomotor apraxia type 2.
these data indicate a potentially causal link among inborn errors in SETX, susceptibility to infection and the development of neurologic disorders.
Title: Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis.
AOA2 with myoclonus associated with mutations in SETX and AFG3L2
Title: An atypical form of AOA2 with myoclonus associated with mutations in SETX and AFG3L2.
BRCA1/SETX complexes support a DNA repair mechanism that addresses R-loop-based DNA damage at transcriptional pause sites.
Title: BRCA1 recruitment to transcriptional pause sites is required for R-loop-driven DNA damage repair.
Results identify novel genes related to senataxin function in normal and disease states.
Title: Mutation of senataxin alters disease-specific transcriptional networks in patients with ataxia with oculomotor apraxia type 2.
genetic variations in the senataxin gene may contribute to Alzheimer's disease pathogenesis in the Taiwanese Han population.
Title: Association of genetic variants in senataxin and Alzheimer's disease in a Chinese Han population in Taiwan.

Submit: New GeneRIF Correction See all GeneRIFs (43)

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

Associated conditions

Description	Tests
Amyotrophic lateral sclerosis type 4 MedGen: C1865409 OMIM: 602433 GeneReviews: Amyotrophic Lateral Sclerosis Overview	Compare labs
Spinocerebellar ataxia autosomal recessive 1 MedGen: C1853761 OMIM: 606002 GeneReviews: Hereditary Ataxia Overview, Ataxia with Oculomotor Apraxia Type 2	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
Interactome of polycomb repressive complex 2 (PRC2), organism-specific biosystem (from WikiPathways)
Interactome of polycomb repressive complex 2 (PRC2), organism-specific biosystemA proposed interactome of Polycomb repressive complex 2 (PRC2), based on proteomics.

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-149376 (e-PCR)
- UniSTS:184920

D9S164 (e-PCR), detects polymorphism
- UniSTS:36197

Cda1bc05 (e-PCR)
- UniSTS:44390

D9S1847 (e-PCR), detects polymorphism
- UniSTS:61336

A008M28 (e-PCR)
- UniSTS:35483

WI-12222 (e-PCR)
- UniSTS:22684

RH91796 (e-PCR)
- UniSTS:86454

D9S1831 (e-PCR)
- UniSTS:27064

SHGC-16732 (e-PCR)
- UniSTS:80869

D9S1073E (e-PCR)
- UniSTS:151291

Homology

Homologs of the SETX gene: The SETX gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 217 organisms have orthologs with human gene SETX
The Hierarchical Catalog of Orthologs

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
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
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

EC 3.6.1.-

NP_001338457.1

EC 3.6.1.-

NP_055861.3

EC 3.6.1.-

XP_005272229.1

EC 3.6.1.-

XP_005272230.1

EC 3.6.1.-

XP_011516706.1

EC 3.6.1.-

XP_011516707.1

EC 3.6.1.-

XP_011516708.1

EC 3.6.1.-

XP_011516709.1

EC 3.6.1.-

XP_011516710.1

EC 3.6.1.-

XP_016869985.1

EC 3.6.1.-

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

NG_007946.1 RefSeqGene

Range

5001..98546

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_268

mRNA and Protein(s)

NM_001351527.1 → 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
NM_001351528.1 → 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
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, ENST00000224140.5

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 Annotation Release 109 details...

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p12 Primary Assembly

Range

132261356..132356726 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Related

ENSP00000409143.1, ENST00000436441.5
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
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
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
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
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
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
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