TISIDB

Summary
Symbol	XRCC4
Name	X-ray repair complementing defective repair in Chinese hamster cells 4
Aliases	X-ray repair, complementing defective, repair in Chinese hamster; DNA repair protein XRCC4; SSMED; X-ray rep ......
Chromosomal Location	5q14.2
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
Domain	PF06632 DNA double-strand break repair and V(D)J recombination protein XRCC4
Function	Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. Binds to DNA and to DNA ligase IV (LIG4). The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.

> Gene Ontology [ TOP ]
Biological Process	GO:0000726 non-recombinational repair GO:0006266 DNA ligation GO:0006302 double-strand break repair GO:0006303 double-strand break repair via nonhomologous end joining GO:0006310 DNA recombination GO:0009314 response to radiation GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0010165 response to X-ray GO:0010212 response to ionizing radiation GO:0010226 response to lithium ion GO:0016925 protein sumoylation GO:0018205 peptidyl-lysine modification GO:0019042 viral latency GO:0019043 establishment of viral latency GO:0051103 DNA ligation involved in DNA repair GO:0051340 regulation of ligase activity GO:0051351 positive regulation of ligase activity GO:0071241 cellular response to inorganic substance GO:0071248 cellular response to metal ion GO:0071285 cellular response to lithium ion GO:0075713 establishment of integrated proviral latency
Molecular Function	GO:0008022 protein C-terminus binding
Cellular Component	GO:0005813 centrosome GO:0005958 DNA-dependent protein kinase-DNA ligase 4 complex GO:0032807 DNA ligase IV complex GO:0070419 nonhomologous end joining complex GO:1990391 DNA repair complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa03450 Non-homologous end-joining
Reactome	R-HSA-164843: 2-LTR circle formation R-HSA-5693532: DNA Double-Strand Break Repair R-HSA-73894: DNA Repair R-HSA-1643685: Disease R-HSA-162594: Early Phase of HIV Life Cycle R-HSA-162906: HIV Infection R-HSA-162587: HIV Life Cycle R-HSA-5663205: Infectious disease R-HSA-162592: Integration of provirus R-HSA-392499: Metabolism of proteins R-HSA-5693571: Nonhomologous End-Joining (NHEJ) R-HSA-597592: Post-translational protein modification R-HSA-3108232: SUMO E3 ligases SUMOylate target proteins R-HSA-2990846: SUMOylation R-HSA-3108214: SUMOylation of DNA damage response and repair proteins

> KEGG and Reactome Pathway

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KEGG

hsa03450 Non-homologous end-joining

Reactome

R-HSA-164843: 2-LTR circle formation
R-HSA-5693532: DNA Double-Strand Break Repair
R-HSA-73894: DNA Repair
R-HSA-1643685: Disease
R-HSA-162594: Early Phase of HIV Life Cycle
R-HSA-162906: HIV Infection
R-HSA-162587: HIV Life Cycle
R-HSA-5663205: Infectious disease
R-HSA-162592: Integration of provirus
R-HSA-392499: Metabolism of proteins
R-HSA-5693571: Nonhomologous End-Joining (NHEJ)
R-HSA-597592: Post-translational protein modification
R-HSA-3108232: SUMO E3 ligases SUMOylate target proteins
R-HSA-2990846: SUMOylation
R-HSA-3108214: SUMOylation of DNA damage response and repair proteins

Summary
Symbol	XRCC4
Name	X-ray repair complementing defective repair in Chinese hamster cells 4
Aliases	X-ray repair, complementing defective, repair in Chinese hamster; DNA repair protein XRCC4; SSMED; X-ray rep ......
Chromosomal Location	5q14.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between XRCC4 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 ]
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Summary
Symbol	XRCC4
Name	X-ray repair complementing defective repair in Chinese hamster cells 4
Aliases	X-ray repair, complementing defective, repair in Chinese hamster; DNA repair protein XRCC4; SSMED; X-ray rep ......
Chromosomal Location	5q14.2
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 XRCC4 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: -2.39; FDR: 0.04170	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	XRCC4
Name	X-ray repair complementing defective repair in Chinese hamster cells 4
Aliases	X-ray repair, complementing defective, repair in Chinese hamster; DNA repair protein XRCC4; SSMED; X-ray rep ......
Chromosomal Location	5q14.2
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 XRCC4 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	-0.069	0.786
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.348	0.808
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.137	0.894
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.292	0.469
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.311	0.786
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.272	0.835
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.042	0.885
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.004	0.997
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.076	0.948
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.518	0.669
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	-0.091	0.957
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.003	0.966

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of XRCC4 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	XRCC4
Name	X-ray repair complementing defective repair in Chinese hamster cells 4
Aliases	X-ray repair, complementing defective, repair in Chinese hamster; DNA repair protein XRCC4; SSMED; X-ray rep ......
Chromosomal Location	5q14.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of XRCC4. 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	XRCC4
Name	X-ray repair complementing defective repair in Chinese hamster cells 4
Aliases	X-ray repair, complementing defective, repair in Chinese hamster; DNA repair protein XRCC4; SSMED; X-ray rep ......
Chromosomal Location	5q14.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of XRCC4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by XRCC4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	XRCC4
Name	X-ray repair complementing defective repair in Chinese hamster cells 4
Aliases	X-ray repair, complementing defective, repair in Chinese hamster; DNA repair protein XRCC4; SSMED; X-ray rep ......
Chromosomal Location	5q14.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of XRCC4. 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	XRCC4
Name	X-ray repair complementing defective repair in Chinese hamster cells 4
Aliases	X-ray repair, complementing defective, repair in Chinese hamster; DNA repair protein XRCC4; SSMED; X-ray rep ......
Chromosomal Location	5q14.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of XRCC4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	XRCC4
Name	X-ray repair complementing defective repair in Chinese hamster cells 4
Aliases	X-ray repair, complementing defective, repair in Chinese hamster; DNA repair protein XRCC4; SSMED; X-ray rep ......
Chromosomal Location	5q14.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between XRCC4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	XRCC4
Name	X-ray repair complementing defective repair in Chinese hamster cells 4
Aliases	X-ray repair, complementing defective, repair in Chinese hamster; DNA repair protein XRCC4; SSMED; X-ray rep ......
Chromosomal Location	5q14.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting XRCC4 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting XRCC4.

ID	Name	Drug Type	Targets	#Targets
DB03963	S-(Dimethylarsenic)Cysteine	Small Molecule	COPG1, NOS3, TLR2, XRCC4	4

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