TISIDB

Summary
Symbol	IL3RA
Name	interleukin 3 receptor, alpha (low affinity)
Aliases	CD123; IL3RY; IL3RX; hIL-3Ra; CD123 antigen; IL-3 receptor alpha SP2 isoform; IL-3 receptor subunit alpha; I ......
Chromosomal Location	Xp22.3 and Yp13.3
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	Membrane; Single-pass type I membrane protein.
Domain	PF09240 Interleukin-6 receptor alpha chain
Function	This is a receptor for interleukin-3.

> Gene Ontology [ TOP ]
Biological Process	GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0036015 response to interleukin-3 GO:0036016 cellular response to interleukin-3 GO:0038156 interleukin-3-mediated signaling pathway
Molecular Function	GO:0004713 protein tyrosine kinase activity GO:0004896 cytokine receptor activity GO:0004912 interleukin-3 receptor activity GO:0005085 guanyl-nucleotide exchange factor activity GO:0005088 Ras guanyl-nucleotide exchange factor activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04151 PI3K-Akt signaling pathway hsa04210 Apoptosis hsa04630 Jak-STAT signaling pathway hsa04640 Hematopoietic cell lineage
Reactome	R-HSA-170984: ARMS-mediated activation R-HSA-422475: Axon guidance R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-2172127: DAP12 interactions R-HSA-2424491: DAP12 signaling R-HSA-1266738: Developmental Biology R-HSA-186763: Downstream signal transduction R-HSA-2871796: FCERI mediated MAPK activation R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-170968: Frs2-mediated activation R-HSA-392451: G beta R-HSA-397795: G-protein beta R-HSA-388396: GPCR downstream signaling R-HSA-114604: GPVI-mediated activation cascade R-HSA-179812: GRB2 events in EGFR signaling R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-109582: Hemostasis R-HSA-2428924: IGF1R signaling cascade R-HSA-112399: IRS-mediated signalling R-HSA-2428928: IRS-related events triggered by IGF1R R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-74751: Insulin receptor signalling cascade R-HSA-912526: Interleukin receptor SHC signaling R-HSA-451927: Interleukin-2 signaling R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-5683057: MAPK family signaling cascades R-HSA-5684996: MAPK1/MAPK3 signaling R-HSA-375165: NCAM signaling for neurite out-growth R-HSA-187037: NGF signalling via TRKA from the plasma membrane R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-169893: Prolonged ERK activation events R-HSA-5673001: RAF/MAP kinase cascade R-HSA-8853659: RET signaling R-HSA-180336: SHC1 events in EGFR signaling R-HSA-112412: SOS-mediated signalling R-HSA-162582: Signal Transduction R-HSA-177929: Signaling by EGFR R-HSA-372790: Signaling by GPCR R-HSA-74752: Signaling by Insulin receptor R-HSA-449147: Signaling by Interleukins R-HSA-2586552: Signaling by Leptin R-HSA-186797: Signaling by PDGF R-HSA-1433557: Signaling by SCF-KIT R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) R-HSA-194138: Signaling by VEGF R-HSA-166520: Signalling by NGF R-HSA-187687: Signalling to ERKs R-HSA-167044: Signalling to RAS R-HSA-187706: Signalling to p38 via RIT and RIN R-HSA-4420097: VEGFA-VEGFR2 Pathway R-HSA-5218921: VEGFR2 mediated cell proliferation

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04060 Cytokine-cytokine receptor interaction
hsa04151 PI3K-Akt signaling pathway
hsa04210 Apoptosis
hsa04630 Jak-STAT signaling pathway
hsa04640 Hematopoietic cell lineage

Reactome

R-HSA-170984: ARMS-mediated activation
R-HSA-422475: Axon guidance
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1266738: Developmental Biology
R-HSA-186763: Downstream signal transduction
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-170968: Frs2-mediated activation
R-HSA-392451: G beta
R-HSA-397795: G-protein beta
R-HSA-388396: GPCR downstream signaling
R-HSA-114604: GPVI-mediated activation cascade
R-HSA-179812: GRB2 events in EGFR signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-109582: Hemostasis
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-912526: Interleukin receptor SHC signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-5683057: MAPK family signaling cascades
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-375165: NCAM signaling for neurite out-growth
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-169893: Prolonged ERK activation events
R-HSA-5673001: RAF/MAP kinase cascade
R-HSA-8853659: RET signaling
R-HSA-180336: SHC1 events in EGFR signaling
R-HSA-112412: SOS-mediated signalling
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-372790: Signaling by GPCR
R-HSA-74752: Signaling by Insulin receptor
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-194138: Signaling by VEGF
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-167044: Signalling to RAS
R-HSA-187706: Signalling to p38 via RIT and RIN
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation

Summary
Symbol	IL3RA
Name	interleukin 3 receptor, alpha (low affinity)
Aliases	CD123; IL3RY; IL3RX; hIL-3Ra; CD123 antigen; IL-3 receptor alpha SP2 isoform; IL-3 receptor subunit alpha; I ......
Chromosomal Location	Xp22.3 and Yp13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IL3RA 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 IL3RA and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
24596416	Acute Myeloid Leukemia	Promote immunity (T cell function); essential for immunotherapy	CD123, the transmembrane α chain of the interleukin-3 receptor, is expressed in the majority of AML cells but is also expressed in many normal hematopoietic cells. Here, we show that CD123 is a good target for AML-directed CAR therapy, because its expression increases over time in vivo even in initially CD123(dim) populations, and that human CD123-redirected T cells (CART123) eradicate primary AML in immunodeficient mice.
24504024	Acute Myeloid Leukemia	Promote immunity (T cell function); essential for immunotherapy	Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. AML cells frequently overexpress the myeloid antigens CD33 and CD123, for which specific CARs can be generated.
27401038	Acute Myeloid Leukemia	Promote immunity	Infusion of CD123-ENG T cells resulted in regression of AML in xenograft models conferring a significant survival advantage of treated mice in comparison to mice that received control T cells.
28576927	Hodgkin Lymphoma	Inhibit immunity (T cell function); essential for immunotherapy	We demonstrated CD123 on both Hodgkin lymphoma cells and TME, including tumor-associated macrophages (TAM).In vitro, Hodgkin lymphoma cells convert macrophages toward immunosuppressive TAMs that inhibit T-cell proliferation. In contrast, anti-CD123 CART recognized and killed TAMs, thus overcoming immunosuppression.
27571406	B Acute Lymphoblastic Leukemia	Promote immunity (T cell function); essential for immunotherapy	Finally, we devised a dual CAR-expressing construct that combined CD19- and CD123-mediated T cell activation and demonstrated that it provides superior in vivo activity against B-ALL compared with single-expressing CART or pooled combination CART. In conclusion, these findings indicate that targeting CD19 and CD123 on leukemic blasts represents an effective strategy for treating and preventing antigen-loss relapses occurring after CD19-directed therapies.
24030378	Acute Myeloid Leukemia	Promote immunity	The interleukin-3 receptor α chain (CD123) has been identified as a potential immunotherapeutic target because it is overexpressed in AML compared with normal hematopoietic stem cells. Additionally, T cells obtained from patients with active AML can be modified to express CD123 CARs and are able to lyse autologous AML blasts in vitro. Finally, CD123 CAR T cells exhibited antileukemic activity in vivo against a xenogeneic model of disseminated AML. These results suggest that CD123 CAR T cells are a promising immunotherapy for the treatment of high-risk AML.

Summary
Symbol	IL3RA
Name	interleukin 3 receptor, alpha (low affinity)
Aliases	CD123; IL3RY; IL3RX; hIL-3Ra; CD123 antigen; IL-3 receptor alpha SP2 isoform; IL-3 receptor subunit alpha; I ......
Chromosomal Location	Xp22.3 and Yp13.3
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

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Statistical results of IL3RA 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	IL3RA
Name	interleukin 3 receptor, alpha (low affinity)
Aliases	CD123; IL3RY; IL3RX; hIL-3Ra; CD123 antigen; IL-3 receptor alpha SP2 isoform; IL-3 receptor subunit alpha; I ......
Chromosomal Location	Xp22.3 and Yp13.3
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 IL3RA 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	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.081	0.865
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.02	0.992
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.164	0.955
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.429	0.355
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.163	0.881
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.624	0.634
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.243	0.34
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	1.899	0.305
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.11	0.403

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IL3RA 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	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
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	7.4	2.7	4.7	0.294
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	7.4	3.4	4	0.587
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	12.5	-12.5	0.52
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	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	IL3RA
Name	interleukin 3 receptor, alpha (low affinity)
Aliases	CD123; IL3RY; IL3RX; hIL-3Ra; CD123 antigen; IL-3 receptor alpha SP2 isoform; IL-3 receptor subunit alpha; I ......
Chromosomal Location	Xp22.3 and Yp13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IL3RA. 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	IL3RA
Name	interleukin 3 receptor, alpha (low affinity)
Aliases	CD123; IL3RY; IL3RX; hIL-3Ra; CD123 antigen; IL-3 receptor alpha SP2 isoform; IL-3 receptor subunit alpha; I ......
Chromosomal Location	Xp22.3 and Yp13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IL3RA. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL3RA. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IL3RA
Name	interleukin 3 receptor, alpha (low affinity)
Aliases	CD123; IL3RY; IL3RX; hIL-3Ra; CD123 antigen; IL-3 receptor alpha SP2 isoform; IL-3 receptor subunit alpha; I ......
Chromosomal Location	Xp22.3 and Yp13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL3RA. 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	IL3RA
Name	interleukin 3 receptor, alpha (low affinity)
Aliases	CD123; IL3RY; IL3RX; hIL-3Ra; CD123 antigen; IL-3 receptor alpha SP2 isoform; IL-3 receptor subunit alpha; I ......
Chromosomal Location	Xp22.3 and Yp13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IL3RA expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IL3RA
Name	interleukin 3 receptor, alpha (low affinity)
Aliases	CD123; IL3RY; IL3RX; hIL-3Ra; CD123 antigen; IL-3 receptor alpha SP2 isoform; IL-3 receptor subunit alpha; I ......
Chromosomal Location	Xp22.3 and Yp13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IL3RA and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IL3RA
Name	interleukin 3 receptor, alpha (low affinity)
Aliases	CD123; IL3RY; IL3RX; hIL-3Ra; CD123 antigen; IL-3 receptor alpha SP2 isoform; IL-3 receptor subunit alpha; I ......
Chromosomal Location	Xp22.3 and Yp13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IL3RA collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting IL3RA.

ID	Name	Drug Type	Targets	#Targets
DB00020	Sargramostim	Biotech	CSF2RA, CSF2RB, IL3RA, PRG2, SDC2	5

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