TISIDB

Summary
Symbol	DNASE1L3
Name	deoxyribonuclease I-like 3
Aliases	DNAS1L3; LSD; DNase gamma; DHP2; SLEB16; DNase I homolog protein 2; DNase I homolog protein DHP2; DNase I-li ......
Chromosomal Location	3p14.3
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 Endoplasmic reticulum Secreted Note=Translocates from the endoplasmic reticulum to the nucleus during apoptosis (PubMed:23229555). Contradictory reports exist about the subcellular localization under normal physiological conditions. Under conditions of cell death, may diffuse and/or be actively transported to the nucleus.
Domain	PF03372 Endonuclease/Exonuclease/phosphatase family
Function	Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends (By similarity). Can cleave chromatin to nucleosomal units and cleaves nucleosomal and liposome-coated DNA (PubMed:9070308, PubMed:9714828, PubMed:14646506, PubMed:10807908, PubMed:27293190). Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis (PubMed:23229555, PubMed:24312463). The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells (By similarity). Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (PubMed:27293190). Together with DNASE1, plays a key role in degrading neutrophil extracellular traps (NETs) (By similarity). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0000737 DNA catabolic process, endonucleolytic GO:0006308 DNA catabolic process GO:0006309 apoptotic DNA fragmentation GO:0006921 cellular component disassembly involved in execution phase of apoptosis GO:0010623 programmed cell death involved in cell development GO:0019439 aromatic compound catabolic process GO:0030262 apoptotic nuclear changes GO:0034655 nucleobase-containing compound catabolic process GO:0044270 cellular nitrogen compound catabolic process GO:0046700 heterocycle catabolic process GO:0090305 nucleic acid phosphodiester bond hydrolysis GO:0097194 execution phase of apoptosis GO:1901361 organic cyclic compound catabolic process
Molecular Function	GO:0004518 nuclease activity GO:0004519 endonuclease activity GO:0004520 endodeoxyribonuclease activity GO:0004536 deoxyribonuclease activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	DNASE1L3
Name	deoxyribonuclease I-like 3
Aliases	DNAS1L3; LSD; DNase gamma; DHP2; SLEB16; DNase I homolog protein 2; DNase I homolog protein DHP2; DNase I-li ......
Chromosomal Location	3p14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between DNASE1L3 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 [ TOP ]
There is no record.

Summary
Symbol	DNASE1L3
Name	deoxyribonuclease I-like 3
Aliases	DNAS1L3; LSD; DNase gamma; DHP2; SLEB16; DNase I homolog protein 2; DNase I homolog protein DHP2; DNase I-li ......
Chromosomal Location	3p14.3
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

[ TOP ]

Statistical results of DNASE1L3 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	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.63	Sensitive to T cell-mediated killing
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	DNASE1L3
Name	deoxyribonuclease I-like 3
Aliases	DNAS1L3; LSD; DNase gamma; DHP2; SLEB16; DNase I homolog protein 2; DNase I homolog protein DHP2; DNase I-li ......
Chromosomal Location	3p14.3
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 DNASE1L3 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	1.082	0.12
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.196	0.318
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.006	0.304
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.285	0.52
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.396	0.711
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.146	0.913
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.057	0.945
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.481	0.686
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.772	0.55
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.568	0.703
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	1.167	0.566
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.595	0.0376

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of DNASE1L3 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	DNASE1L3
Name	deoxyribonuclease I-like 3
Aliases	DNAS1L3; LSD; DNase gamma; DHP2; SLEB16; DNase I homolog protein 2; DNase I homolog protein DHP2; DNase I-li ......
Chromosomal Location	3p14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DNASE1L3. 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	DNASE1L3
Name	deoxyribonuclease I-like 3
Aliases	DNAS1L3; LSD; DNase gamma; DHP2; SLEB16; DNase I homolog protein 2; DNase I homolog protein DHP2; DNase I-li ......
Chromosomal Location	3p14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DNASE1L3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DNASE1L3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	DNASE1L3
Name	deoxyribonuclease I-like 3
Aliases	DNAS1L3; LSD; DNase gamma; DHP2; SLEB16; DNase I homolog protein 2; DNase I homolog protein DHP2; DNase I-li ......
Chromosomal Location	3p14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DNASE1L3. 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	DNASE1L3
Name	deoxyribonuclease I-like 3
Aliases	DNAS1L3; LSD; DNase gamma; DHP2; SLEB16; DNase I homolog protein 2; DNase I homolog protein DHP2; DNase I-li ......
Chromosomal Location	3p14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of DNASE1L3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	DNASE1L3
Name	deoxyribonuclease I-like 3
Aliases	DNAS1L3; LSD; DNase gamma; DHP2; SLEB16; DNase I homolog protein 2; DNase I homolog protein DHP2; DNase I-li ......
Chromosomal Location	3p14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between DNASE1L3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	DNASE1L3
Name	deoxyribonuclease I-like 3
Aliases	DNAS1L3; LSD; DNase gamma; DHP2; SLEB16; DNase I homolog protein 2; DNase I homolog protein DHP2; DNase I-li ......
Chromosomal Location	3p14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting DNASE1L3 collected from DrugBank database.

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

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