TREX1

Protein identityUniProt · HPA

UniProt accession

Q9NSU2

Gene

TREX1

Ensembl

ENSG00000213689

Chromosome

3

Canonical length

314 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted membrane proteins

Subcellular location

Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

314 residues, UniProt reviewed canonical sequence.

>Q9NSU2|TREX1
     1  MGSQALPPGP MQTLIFFDME ATGLPFSQPK VTELCLLAVH RCALESPPTS QGPPPTVPPP
    61  PRVVDKLSLC VAPGKACSPA ASEITGLSTA VLAAHGRQCF DDNLANLLLA FLRRQPQPWC
   121  LVAHNGDRYD FPLLQAELAM LGLTSALDGA FCVDSITALK ALERASSPSE HGPRKSYSLG
   181  SIYTRLYGQS PPDSHTAEGD VLALLSICQW RPQALLRWVD AHARPFGTIR PMYGVTASAR
   241  TKPRPSAVTT TAHLATTRNT SPSLGESRGT KDLPPVKDPG ALSREGLLAP LGLLAILTLA
   301  VATLYGLSLA TPGE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TREX1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

75 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TREX1.

Disease | AllUniProt

Conditions TREX1 is implicated in, by any mechanism.

• Aicardi-Goutieres syndrome 1 (AGS1) MIM:225750
• Systemic lupus erythematosus (SLE) MIM:152700
• Chilblain lupus 1 (CHBL1) MIM:610448
• Vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations (RVCLS) MIM:192315

Disease | GeneticClinVar

79 pathogenic / likely-pathogenic of 613 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Aicardi-Goutieres syndrome 1
• Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations
• Chilblain lupus 1
• Systemic lupus erythematosus
• TREX1-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.69

gnomAD pLI

0.58

gnomAD missense Z

-0.82

DepMap mean gene effect

-0.1

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• activation of immune response
• apoptotic cell clearance
• atrial cardiac muscle tissue development
• blood vessel development
• cellular response to gamma radiation
• cellular response to hydroxyurea
• cellular response to interferon-beta
• cellular response to reactive oxygen species
• defense response to virus
• determination of adult lifespan
• DNA catabolic process
• DNA metabolic process
• DNA modification
• DNA recombination
• DNA repair
• DNA replication
• DNA synthesis involved in UV-damage excision repair
• establishment of protein localization
• generation of precursor metabolites and energy
• glycoprotein biosynthetic process
• heart morphogenesis
• heart process
• inflammatory response to antigenic stimulus
• kidney development
• lymphoid progenitor cell differentiation
• macrophage activation involved in immune response
• mismatch repair
• mitotic G1 DNA damage checkpoint signaling
• negative regulation of cGAS/STING signaling pathway
• negative regulation of innate immune response
• negative regulation of type I interferon-mediated signaling pathway
• protein stabilization
• regulation of cellular respiration
• regulation of fatty acid metabolic process
• regulation of glycolytic process
• regulation of immunoglobulin production
• regulation of inflammatory response
• regulation of lipid biosynthetic process
• regulation of lysosome organization
• regulation of protein complex stability
• regulation of T cell activation
• regulation of tumor necrosis factor production
• regulation of type I interferon production
• retrotransposition
• T cell antigen processing and presentation
• type I interferon-mediated signaling pathway
• immune complex formation
• immune response in brain or nervous system

Molecular functions

• 3'-5' exonuclease activity
• 3'-5'-DNA exonuclease activity
• DNA binding, bending
• double-stranded DNA 3'-5' DNA exonuclease activity
• double-stranded DNA binding
• magnesium ion binding
• metal ion binding
• MutLalpha complex binding
• MutSalpha complex binding
• protein homodimerization activity
• single-stranded DNA binding
• WW domain binding
• adenyl deoxyribonucleotide binding

Cellular components

• cytoplasm
• cytosol
• endoplasmic reticulum membrane
• nuclear envelope
• nuclear replication fork
• oligosaccharyltransferase complex
• protein-DNA complex

Protein domainsUniProt · Pfam · InterPro

• Ribonuclease H-like superfamily
• Ribonuclease H-like domain
• Ribonuclease H superfamily
• Three-prime repair exonuclease 1/2

KeywordsUniProt

• Aicardi-Goutieres syndrome
• Cytoplasm
• Endoplasmic reticulum
• Exonuclease
• Hydrolase
• Magnesium
• Membrane
• Metal-binding
• Neurodegeneration
• Nuclease
• Nucleus
• Phosphoprotein
• Systemic lupus erythematosus
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of TREX1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NME1
• SET
• UBQLN1