TISIDB

Summary
Symbol	IL13RA2
Name	interleukin 13 receptor, alpha 2
Aliases	IL-13R; IL13BP; CD213a2; IL-13 receptor subunit alpha-2; IL-13R subunit alpha-2; IL-13R-alpha-2; IL-13RA2; i ......
Chromosomal Location	Xq23
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	Membrane; Single-pass type I membrane protein.
Domain	PF09240 Interleukin-6 receptor alpha chain
Function	Binds as a monomer with high affinity to interleukin-13 (IL13), but not to interleukin-4 (IL4).

> Gene Ontology [ TOP ]
Biological Process	GO:0002250 adaptive immune response GO:0002263 cell activation involved in immune response GO:0002274 myeloid leukocyte activation GO:0002275 myeloid cell activation involved in immune response GO:0002279 mast cell activation involved in immune response GO:0002366 leukocyte activation involved in immune response GO:0002377 immunoglobulin production GO:0002440 production of molecular mediator of immune response GO:0002443 leukocyte mediated immunity GO:0002444 myeloid leukocyte mediated immunity GO:0002448 mast cell mediated immunity GO:0002449 lymphocyte mediated immunity GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002637 regulation of immunoglobulin production GO:0002638 negative regulation of immunoglobulin production GO:0002683 negative regulation of immune system process GO:0002694 regulation of leukocyte activation GO:0002695 negative regulation of leukocyte activation GO:0002697 regulation of immune effector process GO:0002698 negative regulation of immune effector process GO:0002699 positive regulation of immune effector process GO:0002700 regulation of production of molecular mediator of immune response GO:0002701 negative regulation of production of molecular mediator of immune response GO:0002703 regulation of leukocyte mediated immunity GO:0002704 negative regulation of leukocyte mediated immunity GO:0002886 regulation of myeloid leukocyte mediated immunity GO:0002887 negative regulation of myeloid leukocyte mediated immunity GO:0006887 exocytosis GO:0016064 immunoglobulin mediated immune response GO:0017157 regulation of exocytosis GO:0019724 B cell mediated immunity GO:0032386 regulation of intracellular transport GO:0032387 negative regulation of intracellular transport GO:0032418 lysosome localization GO:0033003 regulation of mast cell activation GO:0033004 negative regulation of mast cell activation GO:0033006 regulation of mast cell activation involved in immune response GO:0033007 negative regulation of mast cell activation involved in immune response GO:0043299 leukocyte degranulation GO:0043300 regulation of leukocyte degranulation GO:0043301 negative regulation of leukocyte degranulation GO:0043303 mast cell degranulation GO:0043304 regulation of mast cell degranulation GO:0043305 negative regulation of mast cell degranulation GO:0045055 regulated exocytosis GO:0045576 mast cell activation GO:0045920 negative regulation of exocytosis GO:0050777 negative regulation of immune response GO:0050865 regulation of cell activation GO:0050866 negative regulation of cell activation GO:0051048 negative regulation of secretion GO:0051051 negative regulation of transport GO:0051640 organelle localization GO:0051656 establishment of organelle localization GO:0060627 regulation of vesicle-mediated transport GO:1903305 regulation of regulated secretory pathway GO:1903306 negative regulation of regulated secretory pathway GO:1903531 negative regulation of secretion by cell
Molecular Function	GO:0004896 cytokine receptor activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04630 Jak-STAT signaling pathway
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-6785807: Interleukin-4 and 13 signaling R-HSA-449147: Signaling by Interleukins

Summary
Symbol	IL13RA2
Name	interleukin 13 receptor, alpha 2
Aliases	IL-13R; IL13BP; CD213a2; IL-13 receptor subunit alpha-2; IL-13R subunit alpha-2; IL-13R-alpha-2; IL-13RA2; i ......
Chromosomal Location	Xq23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IL13RA2 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 IL13RA2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27427982	Glioblastoma	Promote immunity (T cell function)	We observed that TanCARs engaged HER2 and IL13Rα2 simultaneously by inducing HER2-IL13Rα2 heterodimers, which promoted superadditive T cell activation when both antigens were encountered concurrently. We determined that patient TanCAR T cells showed distinct binding to HER2 or IL13Rα2 and had the capability to lyse autologous glioblastoma.Thus, TanCAR T cells show therapeutic potential to improve glioblastoma control by coengaging HER2 and IL13Rα2 in an augmented, bivalent immune synapse that enhances T cell functionality and reduces antigen escape.
22407828	Glioma	Promote immunity (T cell function); essential for immunotherapy	We observed that although glioma IL13Rα2 expression varies between patients, for IL13Rα2(pos) cases this antigen was detected on both GSCs and more differentiated tumor cell populations. IL13-zetakine(+) CTL were capable of efficient recognition and killing of both IL13Rα2(pos) GSCs and IL13Rα2(pos) differentiated cells in vitro, as well as eliminating glioma-initiating activity in an orthotopic mouse tumor model.
23939024	Glioblastoma	Promote immunity	This mathematical model demonstrated that cotargeting HER2 and IL-13Rα2 could maximally expand the therapeutic reach of the T cell product in all primary tumors studied. Further, T cells coexpressing HER2 and IL-13Rα2-CARs exhibited accentuated yet antigen-dependent downstream signaling and a particularly enhanced antitumor activity.
21357681	Lung Carcinoma; Mesothelioma	Promote immunity	This augmented expression of IL-13Rα2 resulted in growth inhibition of the mesothelioma cells when cocultured with anti-IL-13Rα2 and effector cells, such as splenocytes and peritoneal exudate cells. These observations indicate a promising role for IL-13Rα2 as a target for antibody treatment in malignant mesothelioma, and, in combination with epigenetic regulation by a DNA methylation inhibitor, suggest the potential for a novel strategy to enhance therapeutic potency.
16899618	Contralateral	Promote immunity	When animals with IL-13Ralpha2-expressing D5 tumor (right) were injected with IL13-PE38, right flank tumors expressing the IL-13Ralpha2 chain not only showed dramatic regression but contralateral tumors (left flank) also showed tumor regression.

Summary
Symbol	IL13RA2
Name	interleukin 13 receptor, alpha 2
Aliases	IL-13R; IL13BP; CD213a2; IL-13 receptor subunit alpha-2; IL-13R subunit alpha-2; IL-13R-alpha-2; IL-13RA2; i ......
Chromosomal Location	Xq23
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 IL13RA2 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	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	IL13RA2
Name	interleukin 13 receptor, alpha 2
Aliases	IL-13R; IL13BP; CD213a2; IL-13 receptor subunit alpha-2; IL-13R subunit alpha-2; IL-13R-alpha-2; IL-13RA2; i ......
Chromosomal Location	Xq23
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 IL13RA2 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	-0.45	0.648
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-2.19	0.186
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.805	0.593
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.27	0.116
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.785	0.134
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.633	0.644
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.883	0.452
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.33	0.843
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	2.408	0.162
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-1.523	0.169
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	-0.868	0.538
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.037	0.898

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IL13RA2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	7.4	0.0709
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	7.4	0.096
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	IL13RA2
Name	interleukin 13 receptor, alpha 2
Aliases	IL-13R; IL13BP; CD213a2; IL-13 receptor subunit alpha-2; IL-13R subunit alpha-2; IL-13R-alpha-2; IL-13RA2; i ......
Chromosomal Location	Xq23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IL13RA2. 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	IL13RA2
Name	interleukin 13 receptor, alpha 2
Aliases	IL-13R; IL13BP; CD213a2; IL-13 receptor subunit alpha-2; IL-13R subunit alpha-2; IL-13R-alpha-2; IL-13RA2; i ......
Chromosomal Location	Xq23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IL13RA2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL13RA2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IL13RA2
Name	interleukin 13 receptor, alpha 2
Aliases	IL-13R; IL13BP; CD213a2; IL-13 receptor subunit alpha-2; IL-13R subunit alpha-2; IL-13R-alpha-2; IL-13RA2; i ......
Chromosomal Location	Xq23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL13RA2. 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	IL13RA2
Name	interleukin 13 receptor, alpha 2
Aliases	IL-13R; IL13BP; CD213a2; IL-13 receptor subunit alpha-2; IL-13R subunit alpha-2; IL-13R-alpha-2; IL-13RA2; i ......
Chromosomal Location	Xq23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IL13RA2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IL13RA2
Name	interleukin 13 receptor, alpha 2
Aliases	IL-13R; IL13BP; CD213a2; IL-13 receptor subunit alpha-2; IL-13R subunit alpha-2; IL-13R-alpha-2; IL-13RA2; i ......
Chromosomal Location	Xq23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IL13RA2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IL13RA2
Name	interleukin 13 receptor, alpha 2
Aliases	IL-13R; IL13BP; CD213a2; IL-13 receptor subunit alpha-2; IL-13R subunit alpha-2; IL-13R-alpha-2; IL-13RA2; i ......
Chromosomal Location	Xq23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IL13RA2 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting IL13RA2.

ID	Name	Drug Type	Targets	#Targets
DB05078	AER001	Small Molecule	IL13RA2, IL4R	2

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