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; AllianceGenome:HGNC:445
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; STEX; 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

Location:: 9q34.13

Exon count:: 33

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (132261356..132356744, complement)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (144475833..144569459, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (135136743..135230373, 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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Mutation in senataxin alters the mechanism of R-loop resolution in amyotrophic lateral sclerosis 4.
Title: Mutation in senataxin alters the mechanism of R-loop resolution in amyotrophic lateral sclerosis 4.
DeltaNp63-Senataxin circuit controls keratinocyte differentiation by promoting the transcriptional termination of epidermal genes.
Title: ΔNp63-Senataxin circuit controls keratinocyte differentiation by promoting the transcriptional termination of epidermal genes.
Integrated genome and transcriptome analyses reveal the mechanism of genome instability in ataxia with oculomotor apraxia 2.
Title: Integrated genome and transcriptome analyses reveal the mechanism of genome instability in ataxia with oculomotor apraxia 2.
USP11 controls R-loops by regulating senataxin proteostasis.
Title: USP11 controls R-loops by regulating senataxin proteostasis.
Evidence of synergism among three genetic variants in a patient with LMNA-related lipodystrophy and amyotrophic lateral sclerosis leading to a remarkable nuclear phenotype.
Title: Evidence of synergism among three genetic variants in a patient with LMNA-related lipodystrophy and amyotrophic lateral sclerosis leading to a remarkable nuclear phenotype.
Hypoxia-induced SETX links replication stress with the unfolded protein response.
Title: Hypoxia-induced SETX links replication stress with the unfolded protein response.
Rare phenotype of ALS4 associated with heterozygous missense mutation c.5842A > G/p.M1948V in helicase domain of SETX gene.
Title: Rare phenotype of ALS4 associated with heterozygous missense mutation c.5842A > G/p.M1948V in helicase domain of <i>SETX</i> gene.
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.
Some pathogenic SETX variants are partially conserved during evolution.
Title: Some pathogenic SETX variants are partially conserved during evolution.
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.

Submit: New GeneRIF Correction See all GeneRIFs (59)

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, with axonal neuropathy 2 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)

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: 361 organisms have orthologs with human gene SETX
Orthologs

Clone Names

FLJ12840, FLJ43459, KIAA0625, DKFZp781B151

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables DNA binding	IC Inferred by Curator more info	PubMed
enables DNA helicase activity	TAS Traceable Author Statement more info	PubMed
enables RNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription termination site sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables transcription termination site sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA duplex unwinding	IEA Inferred from Electronic Annotation more info
involved_in DNA recombination	IEA Inferred from Electronic Annotation more info
involved_in DNA-templated transcription termination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in RNA processing	TAS Traceable Author Statement more info	PubMed
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to DNA damage stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to fibroblast growth factor stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to hydrogen peroxide	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to retinoic acid	IDA Inferred from Direct Assay more info	PubMed
involved_in circadian rhythm	IEA Inferred from Electronic Annotation more info
involved_in double-strand break repair	IDA Inferred from Direct Assay more info	PubMed
involved_in fibroblast growth factor receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in mRNA splice site selection	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in nervous system development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription initiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of RNA splicing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neuron projection development	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of termination of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of termination of RNA polymerase II transcription, poly(A)-coupled	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein kinase B signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info
involved_in termination of RNA polymerase II transcription	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in chromosome, telomeric region	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in growth cone	IDA Inferred from Direct Assay more info	PubMed
located_in intercellular bridge	IDA Inferred from Direct Assay more info
is_active_in nuclear body	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nuclear chromosome	IDA Inferred from Direct Assay more info	PubMed
located_in nucleolus	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in 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_047278979.1

EC 3.6.1.-

XP_047278980.1

EC 3.6.1.-

XP_047278981.1

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_001351527.2 → 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

UniProtKB/Swiss-Prot

Q9NVP9

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_001351528.2 → 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
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, Q9NVP9

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 Annotation Release 110 details...

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

132261356..132356744 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005272172.4 → 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_011518404.4 → 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_047423023.1 → XP_047278979.1 probable helicase senataxin isoform X2

UniProtKB/Swiss-Prot

Q9NVP9
XM_011518405.4 → 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_005272173.4 → 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_011518406.3 → XP_011516708.1 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

pfam13087
Location:2225 → 2400

AAA_12; AAA domain

pfam13245
Location:1957 → 2020

AAA_19; Part of AAA domain
XM_011518407.2 → XP_011516709.1 probable helicase senataxin isoform X4

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_011518408.4 → XP_011516710.1 probable helicase senataxin isoform X5

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
XM_047423025.1 → XP_047278981.1 probable helicase senataxin isoform X7
XM_047423024.1 → XP_047278980.1 probable helicase senataxin isoform X6