TREX1 three prime repair exonuclease 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TREX1provided by HGNC
Official Full Name: three prime repair exonuclease 1provided by HGNC
Primary source: HGNC:HGNC:12269
See related: Ensembl:ENSG00000213689 MIM:606609
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: CRV; AGS1; DRN3; HERNS
Summary: This gene encodes a nuclear protein with 3' exonuclease activity. The encoded protein may play a role in DNA repair and serve as a proofreading function for DNA polymerase. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, Cree encephalitis, and other diseases of the immune system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]
Annotation information: Note: GeneID 11277 was annotated as a single gene with two non-overlapping coding regions. GeneID 11277 now represents only the downstream coding region encoding three prime repair exonuclease 1. The upstream coding region is represented by geneID 84126. [29 May 2007]
Expression: Ubiquitous expression in spleen (RPKM 9.5), lymph node (RPKM 7.7) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 3p21.31

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
109.20200228	current	GRCh38.p13 (GCF_000001405.39)	3	NC_000003.12 (48465830..48467645)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (48506919..48509044)

Chromosome 3 - NC_000003.12 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?

Familial cryofibrinogenemia without lupus should be added to the spectrum of TREX1-related disease.
Title: TREX-1-Related Disease Associated with the Presence of Cryofibrinogenemia.
TREX1 mutation is the cause for the Aicardi goutieres syndrome associated pulmonary hypertension.
Title: Aicardi goutières syndrome is associated with pulmonary hypertension.
These findings suggest a role for TREX1(+) microglia in vessel homeostasis and response to ischemic injury.
Title: TREX1 is expressed by microglia in normal human brain and increases in regions affected by ischemia.
data identifies miR-103 regulation of TREX1 as a potent modulator of the tumour microenvironment.
Title: MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment.
Thus, the intracellular level of TREX1 pivotally modulates innate immune induction by HIV-1. Partial HIV-1 genomes are the TREX1 target and are sensed by cGAS.
Title: HIV-1 Activation of Innate Immunity Depends Strongly on the Intracellular Level of TREX1 and Sensing of Incomplete Reverse Transcription Products.
TREX1-deficient neurons also exhibited increased apoptosis and formed three-dimensional cortical organoids of reduced size.
Title: Modeling of TREX1-Dependent Autoimmune Disease using Human Stem Cells Highlights L1 Accumulation as a Source of Neuroinflammation.
Homozygote R114C mutation in TREX1 gene was shown in two siblings, one with chilblains and another with chilblains accompanied with cerebral vasculitis.
Title: A homozygote TREX1 mutation in two siblings with different phenotypes: Chilblains and cerebral vasculitis.
TREX1 frame-shift mutations induce autoantibodies against mostly non-nuclear antigens, patients carrying these mutations are likely be ANA negative
Title: DNase-active TREX1 frame-shift mutants induce serologic autoimmunity in mice.
The activation of interferon-induced genes is controlled by the JAK-STAT system; therefore, JAK inhibitors were successfully used in several cases to treat type 1 interferonopathies. Experience with this treatment modality is continuously growing.
Title: [Familial chilblain lupus : Type 1 interferonopathy with model character].
TheTREX1 and STING, which are opposing regulators of the cytosolic DNA-sensing pathway.
Title: Immune Diseases Associated with TREX1 and STING Dysfunction.

Submit: New GeneRIF Correction See all GeneRIFs (67)

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
Aicardi Goutieres syndrome 1 MedGen: C0796126 OMIM: 225750 GeneReviews: Aicardi-Goutieres Syndrome	Compare labs
Chilblain lupus 1 MedGen: C3277619 OMIM: 610448 GeneReviews: Not available	Compare labs
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations MedGen: C1860518 OMIM: 192315 GeneReviews: Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations	Compare labs
Systemic lupus erythematosus MedGen: C0024141 OMIM: 152700 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 replication requires TREX1 expression in human cervicovaginal explants as shown through TREX1 knockdown	PubMed
SiRNA-mediated knockdown of one of the components of the SET complex, TREX1, inhibits HIV-1 infection with significantly reduced levels of integrated HIV-1 DNA and viral production in HeLa-CD4 cells, human cervicovaginal explants or humanized mice	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D3S3563 (e-PCR)
- UniSTS:7188

TREX1_1109 (e-PCR)
- UniSTS:277844

WI-11814 (e-PCR)
- UniSTS:56934

STS-Z41083 (e-PCR)
- UniSTS:16802

WI-21042 (e-PCR)
- UniSTS:37556

Readthrough ATRIP-TREX1

Readthrough gene: ATRIP-TREX1, Included gene: ATRIP

Homology

Homologs of the TREX1 gene: The TREX1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Orthologs from Annotation Pipeline: 141 organisms have orthologs with human gene TREX1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
3'-5' exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
3'-5'-exodeoxyribonuclease activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
3'-5'-exodeoxyribonuclease activity	ISS Inferred from Sequence or Structural Similarity more info
DNA binding, bending	IEA Inferred from Electronic Annotation more info
MutLalpha complex binding	IDA Inferred from Direct Assay more info	PubMed
MutSalpha complex binding	IDA Inferred from Direct Assay more info	PubMed
WW domain binding	IEA Inferred from Electronic Annotation more info
adenyl deoxyribonucleotide binding	IEA Inferred from Electronic Annotation more info
double-stranded DNA binding	IEA Inferred from Electronic Annotation more info
exodeoxyribonuclease III activity	IEA Inferred from Electronic Annotation more info
magnesium ion binding	IEA Inferred from Electronic Annotation more info
metal ion binding	NAS Non-traceable Author Statement more info	PubMed
protein homodimerization activity	IEA Inferred from Electronic Annotation more info
single-stranded DNA binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
CD86 biosynthetic process	IEA Inferred from Electronic Annotation more info
DNA catabolic process	IEA Inferred from Electronic Annotation more info
DNA duplex unwinding	IEA Inferred from Electronic Annotation more info
DNA metabolic process	ISS Inferred from Sequence or Structural Similarity more info
DNA modification	IEA Inferred from Electronic Annotation more info
DNA recombination	NAS Non-traceable Author Statement more info	PubMed
DNA repair	TAS Traceable Author Statement more info	PubMed
DNA replication	NAS Non-traceable Author Statement more info	PubMed
DNA synthesis involved in UV-damage excision repair	IEA Inferred from Electronic Annotation more info
T cell antigen processing and presentation	IEA Inferred from Electronic Annotation more info
activation of immune response	IEA Inferred from Electronic Annotation more info
apoptotic cell clearance	IEA Inferred from Electronic Annotation more info
atrial cardiac muscle tissue development	IEA Inferred from Electronic Annotation more info
blood vessel development	IEA Inferred from Electronic Annotation more info
cellular response to gamma radiation	IEA Inferred from Electronic Annotation more info
cellular response to hydroxyurea	IEA Inferred from Electronic Annotation more info
cellular response to interferon-beta	IEA Inferred from Electronic Annotation more info
cellular response to reactive oxygen species	IEA Inferred from Electronic Annotation more info
defense response to virus	IEA Inferred from Electronic Annotation more info
detection of DNA damage stimulus involved in DNA damage checkpoint	IEA Inferred from Electronic Annotation more info
detection of stimulus involved in cell cycle checkpoint	IEA Inferred from Electronic Annotation more info
determination of adult lifespan	IEA Inferred from Electronic Annotation more info
establishment of protein localization	IEA Inferred from Electronic Annotation more info
generation of precursor metabolites and energy	IEA Inferred from Electronic Annotation more info
heart morphogenesis	IEA Inferred from Electronic Annotation more info
heart process	IEA Inferred from Electronic Annotation more info
immune complex formation	IEA Inferred from Electronic Annotation more info
immune response in brain or nervous system	IEA Inferred from Electronic Annotation more info
immunoglobulin biosynthetic process involved in immune response	IEA Inferred from Electronic Annotation more info
inflammatory response to antigenic stimulus	IEA Inferred from Electronic Annotation more info
interferon-alpha production	IEA Inferred from Electronic Annotation more info
kidney development	IEA Inferred from Electronic Annotation more info
lymphoid progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
macrophage activation involved in immune response	IEA Inferred from Electronic Annotation more info
mismatch repair	NAS Non-traceable Author Statement more info	PubMed
negative regulation of type I interferon-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
nucleic acid phosphodiester bond hydrolysis	IEA Inferred from Electronic Annotation more info
protein stabilization	IEA Inferred from Electronic Annotation more info
regulation of T cell activation	IEA Inferred from Electronic Annotation more info
regulation of catalytic activity	IEA Inferred from Electronic Annotation more info
regulation of cellular respiration	IEA Inferred from Electronic Annotation more info
regulation of fatty acid metabolic process	IEA Inferred from Electronic Annotation more info
regulation of gene expression	IEA Inferred from Electronic Annotation more info
regulation of glycolytic process	IEA Inferred from Electronic Annotation more info
regulation of immunoglobulin production	IEA Inferred from Electronic Annotation more info
regulation of inflammatory response	IEA Inferred from Electronic Annotation more info
regulation of lipid biosynthetic process	IEA Inferred from Electronic Annotation more info
regulation of lysosome organization	IEA Inferred from Electronic Annotation more info
regulation of protein complex stability	IEA Inferred from Electronic Annotation more info
regulation of tumor necrosis factor production	IEA Inferred from Electronic Annotation more info
regulation of type I interferon production	TAS Traceable Author Statement more info
signal transduction involved in DNA damage checkpoint	IEA Inferred from Electronic Annotation more info
transposition, RNA-mediated	IEA Inferred from Electronic Annotation more info
type I interferon signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytosol	IDA Inferred from Direct Assay more info
endoplasmic reticulum membrane	TAS Traceable Author Statement more info
nuclear envelope	NAS Non-traceable Author Statement more info	PubMed
nuclear replication fork	IEA Inferred from Electronic Annotation more info
oligosaccharyltransferase complex	IEA Inferred from Electronic Annotation more info
protein-DNA complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: three-prime repair exonuclease 1

Names: 3' repair exonuclease 1; 3'-5' exonuclease TREX1; DNase III; deoxyribonuclease III

NP_009179.2

EC 3.1.11.2

NP_338599.1

EC 3.1.11.2

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_009820.2 RefSeqGene

Range

5401..6816

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_007248.5 → NP_009179.2 three-prime repair exonuclease 1 isoform c

See identical proteins and their annotated locations for NP_009179.2

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate splice site in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The resulting isoform (c) has a shorter N-terminus, compared to isoform a.

Source sequence(s)

AC134772, AF319566, AF319569, AJ243797, BT020053, W24304

Consensus CDS

CCDS59451.1

UniProtKB/Swiss-Prot

Q9NSU2

UniProtKB/TrEMBL

Q5TZT0

Related

ENSP00000415972.1, ENST00000444177.1

Conserved Domains (1) summary

cl10012
Location:4 → 201

DnaQ_like_exo; DnaQ-like (or DEDD) 3'-5' exonuclease domain superfamily
NM_033629.6 → NP_338599.1 three-prime repair exonuclease 1 isoform b

See identical proteins and their annotated locations for NP_338599.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice site in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The resulting isoform (b) has a shorter N-terminus, compared to isoform a.

Source sequence(s)

AF319569, AL137745, BT020053

Consensus CDS

CCDS2769.1

UniProtKB/Swiss-Prot

Q9NSU2

Related

ENSP00000486676.2, ENST00000625293.3

Conserved Domains (1) summary

cl10012
Location:14 → 211

DnaQ_like_exo; DnaQ-like (or DEDD) 3'-5' exonuclease domain superfamily

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p13 Primary Assembly

Range

48465830..48467645

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_016381.5: Suppressed sequence

Description

NM_016381.5: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.
NM_033627.3: Suppressed sequence

Description

NM_033627.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript, which represents a rare readthrough event.
NM_033628.2: Suppressed sequence

Description

NM_033628.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript, which represents a rare readthrough event.