TISIDB

Summary
Symbol	TREX1
Name	three prime repair exonuclease 1
Aliases	DRN3; Aicardi-Goutieres syndrome 1; CRV; HERNS; 3' repair exonuclease 1; 3'-5' exonuclease TREX1; DNase III; ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus. Cytoplasm, cytosol. Endoplasmic reticulum membrane; Peripheral membrane protein. Note=Retained in the cytoplasm through the C-terminal region (By similarity). In response to DNA damage, translocates to the nucleus where it is specifically recruited to replication foci. Translocation to the nucleus also occurs during GZMA-mediated cell death.
Domain	-
Function	Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini. Prevents cell-intrinsic initiation of autoimmunity. Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements. Unless degraded, these DNA fragments accumulate in the cytosol and activate the IFN-stimulatory DNA (ISD) response and innate immune signaling. Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the processing of aberrant DNA replication intermediates. Inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light. During GZMA-mediated cell death, contributes to DNA damage in concert with NME1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair.

> Gene Ontology [ TOP ]
Biological Process	-
Molecular Function	-
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04623 Cytosolic DNA-sensing pathway
Reactome	R-HSA-1834949: Cytosolic sensors of pathogen-associated DNA R-HSA-3270619: IRF3-mediated induction of type I IFN R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-3248023: Regulation by TREX1 R-HSA-3134975: Regulation of innate immune responses to cytosolic DNA R-HSA-1834941: STING mediated induction of host immune responses

Summary
Symbol	TREX1
Name	three prime repair exonuclease 1
Aliases	DRN3; Aicardi-Goutieres syndrome 1; CRV; HERNS; 3' repair exonuclease 1; 3'-5' exonuclease TREX1; DNase III; ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TREX1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between TREX1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28598415	Breast Carcinoma; Colorectal Carcinoma	Inhibit immunity (infiltration); Resistant to immunotherapy.	We show that the DNA exonuclease Trex1 is induced by radiation doses above 12-18 Gy in different cancer cells, and attenuates their immunogenicity by degrading DNA that accumulates in the cytosol upon radiation. Repeated irradiation at doses that do not induce Trex1 amplifies interferon-β production, resulting in recruitment and activation of Batf3-dependent dendritic cells.

Summary
Symbol	TREX1
Name	three prime repair exonuclease 1
Aliases	DRN3; Aicardi-Goutieres syndrome 1; CRV; HERNS; 3' repair exonuclease 1; 3'-5' exonuclease TREX1; DNase III; ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of TREX1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	logFC: -2.67; FDR: 0.04630	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	TREX1
Name	three prime repair exonuclease 1
Aliases	DRN3; Aicardi-Goutieres syndrome 1; CRV; HERNS; 3' repair exonuclease 1; 3'-5' exonuclease TREX1; DNase III; ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of TREX1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.078	0.817
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.153	0.923
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.247	0.833
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.144	0.63
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.268	0.887
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.007	0.998
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0	1
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.849	0.559
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.138	0.604
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.024	0.798

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TREX1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	TREX1
Name	three prime repair exonuclease 1
Aliases	DRN3; Aicardi-Goutieres syndrome 1; CRV; HERNS; 3' repair exonuclease 1; 3'-5' exonuclease TREX1; DNase III; ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TREX1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	TREX1
Name	three prime repair exonuclease 1
Aliases	DRN3; Aicardi-Goutieres syndrome 1; CRV; HERNS; 3' repair exonuclease 1; 3'-5' exonuclease TREX1; DNase III; ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TREX1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TREX1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TREX1
Name	three prime repair exonuclease 1
Aliases	DRN3; Aicardi-Goutieres syndrome 1; CRV; HERNS; 3' repair exonuclease 1; 3'-5' exonuclease TREX1; DNase III; ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TREX1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	TREX1
Name	three prime repair exonuclease 1
Aliases	DRN3; Aicardi-Goutieres syndrome 1; CRV; HERNS; 3' repair exonuclease 1; 3'-5' exonuclease TREX1; DNase III; ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TREX1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TREX1
Name	three prime repair exonuclease 1
Aliases	DRN3; Aicardi-Goutieres syndrome 1; CRV; HERNS; 3' repair exonuclease 1; 3'-5' exonuclease TREX1; DNase III; ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TREX1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TREX1
Name	three prime repair exonuclease 1
Aliases	DRN3; Aicardi-Goutieres syndrome 1; CRV; HERNS; 3' repair exonuclease 1; 3'-5' exonuclease TREX1; DNase III; ......
Chromosomal Location	3p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TREX1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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