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; AllianceGenome:HGNC:12269
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; RVCLS
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
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Genomic context

Location:: 3p21.31

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_03	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (48465830..48467645)
RS_2023_03	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (48493835..48495650)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (48507229..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?

TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients.
Title: TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients.
Structural basis of human TREX1 DNA degradation and autoimmune disease.
Title: Structural basis of human TREX1 DNA degradation and autoimmune disease.
TREX1 plays multiple roles in human diseases.
Title: TREX1 plays multiple roles in human diseases.
Photosensitivity and cGAS-Dependent IFN-1 Activation in Patients with Lupus and TREX1 Deficiency.
Title: Photosensitivity and cGAS-Dependent IFN-1 Activation in Patients with Lupus and TREX1 Deficiency.
TREX1 degrades the 3' end of the small DNA oligonucleotide products of nucleotide excision repair in human cells.
Title: TREX1 degrades the 3' end of the small DNA oligonucleotide products of nucleotide excision repair in human cells.
Human TDP1, APE1 and TREX1 repair 3'-DNA-peptide/protein cross-links arising from abasic sites in vitro.
Title: Human TDP1, APE1 and TREX1 repair 3'-DNA-peptide/protein cross-links arising from abasic sites in vitro.
Carboplatin activates the cGAS-STING pathway by upregulating the TREX-1 (three prime repair exonuclease 1) expression in human melanoma.
Title: Carboplatin activates the cGAS-STING pathway by upregulating the TREX-1 (three prime repair exonuclease 1) expression in human melanoma.
Compromised nuclear envelope integrity drives TREX1-dependent DNA damage and tumor cell invasion.
Title: Compromised nuclear envelope integrity drives TREX1-dependent DNA damage and tumor cell invasion.
Hepatitis B virus nucleocapsid uncoating: biological consequences and regulation by cellular nucleases.
Title: Hepatitis B virus nucleocapsid uncoating: biological consequences and regulation by cellular nucleases.
TREX1 as a Novel Immunotherapeutic Target.
Title: TREX1 as a Novel Immunotherapeutic Target.

Submit: New GeneRIF Correction See all GeneRIFs (88)

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: C0024145 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

EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS 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

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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: 206 organisms have orthologs with human gene TREX1
Orthologs

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in CD86 biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in DNA duplex unwinding	IEA Inferred from Electronic Annotation more info
involved_in DNA metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in DNA modification	IEA Inferred from Electronic Annotation more info
involved_in DNA recombination	NAS Non-traceable Author Statement more info	PubMed
involved_in DNA repair	TAS Traceable Author Statement more info	PubMed
involved_in DNA replication	NAS Non-traceable Author Statement more info	PubMed
involved_in DNA synthesis involved in UV-damage excision repair	IEA Inferred from Electronic Annotation more info
involved_in T cell antigen processing and presentation	IEA Inferred from Electronic Annotation more info
involved_in activation of immune response	IEA Inferred from Electronic Annotation more info
involved_in apoptotic cell clearance	IEA Inferred from Electronic Annotation more info
involved_in atrial cardiac muscle tissue development	IEA Inferred from Electronic Annotation more info
involved_in blood vessel development	IEA Inferred from Electronic Annotation more info
involved_in cellular response to gamma radiation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hydroxyurea	IEA Inferred from Electronic Annotation more info
involved_in cellular response to interferon-beta	IEA Inferred from Electronic Annotation more info
involved_in cellular response to reactive oxygen species	IEA Inferred from Electronic Annotation more info
involved_in defense response to virus	IEA Inferred from Electronic Annotation more info
involved_in determination of adult lifespan	IEA Inferred from Electronic Annotation more info
involved_in establishment of protein localization	IEA Inferred from Electronic Annotation more info
involved_in generation of precursor metabolites and energy	IEA Inferred from Electronic Annotation more info
involved_in heart morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in heart process	IEA Inferred from Electronic Annotation more info
involved_in immune complex formation	IEA Inferred from Electronic Annotation more info
involved_in immune response in brain or nervous system	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response to antigenic stimulus	IEA Inferred from Electronic Annotation more info
involved_in kidney development	IEA Inferred from Electronic Annotation more info
involved_in lymphoid progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in macrophage activation involved in immune response	IEA Inferred from Electronic Annotation more info
involved_in mismatch repair	NAS Non-traceable Author Statement more info	PubMed
involved_in mitotic G1 DNA damage checkpoint signaling	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of type I interferon-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in protein stabilization	IEA Inferred from Electronic Annotation more info
involved_in regulation of T cell activation	IEA Inferred from Electronic Annotation more info
involved_in regulation of catalytic activity	IEA Inferred from Electronic Annotation more info
involved_in regulation of cellular respiration	IEA Inferred from Electronic Annotation more info
involved_in regulation of fatty acid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of glycolytic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of immunoglobulin production	IEA Inferred from Electronic Annotation more info
involved_in regulation of inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in regulation of lipid biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of lysosome organization	IEA Inferred from Electronic Annotation more info
involved_in regulation of protein complex stability	IEA Inferred from Electronic Annotation more info
involved_in regulation of tumor necrosis factor production	IEA Inferred from Electronic Annotation more info
involved_in regulation of type I interferon production	IEA Inferred from Electronic Annotation more info
involved_in retrotransposition	IEA Inferred from Electronic Annotation more info
involved_in type I interferon-mediated signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in nuclear envelope	NAS Non-traceable Author Statement more info	PubMed
located_in nuclear replication fork	IEA Inferred from Electronic Annotation more info
part_of oligosaccharyltransferase complex	IEA Inferred from Electronic Annotation more info
part_of 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

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_282

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, Q9Y4X2

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: GCF_000001405.40-RS_2023_03

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

48465830..48467645

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

48493835..48495650

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.