TISIDB

Summary
Symbol	IL3
Name	interleukin 3
Aliases	IL-3; MULTI-CSF; MCGF; MGC79398; MGC79399; multilineage-colony-stimulating factor; hematopoietic growth fact ......
Chromosomal Location	5q31.1
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	Secreted.
Domain	PF02059 Interleukin-3
Function	Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages.; FUNCTION: This CSF induces granulocytes, macrophages, mast cells, stem cells, erythroid cells, eosinophils and megakaryocytes.

> Gene Ontology [ TOP ]
Biological Process	GO:0002521 leukocyte differentiation GO:0002573 myeloid leukocyte differentiation GO:0002761 regulation of myeloid leukocyte differentiation GO:0002763 positive regulation of myeloid leukocyte differentiation GO:0006260 DNA replication GO:0006275 regulation of DNA replication GO:0007259 JAK-STAT cascade GO:0007260 tyrosine phosphorylation of STAT protein GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0030099 myeloid cell differentiation GO:0035162 embryonic hemopoiesis GO:0042506 tyrosine phosphorylation of Stat5 protein GO:0042509 regulation of tyrosine phosphorylation of STAT protein GO:0042522 regulation of tyrosine phosphorylation of Stat5 protein GO:0042523 positive regulation of tyrosine phosphorylation of Stat5 protein GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein GO:0045637 regulation of myeloid cell differentiation GO:0045639 positive regulation of myeloid cell differentiation GO:0045740 positive regulation of DNA replication GO:0046425 regulation of JAK-STAT cascade GO:0046427 positive regulation of JAK-STAT cascade GO:0048568 embryonic organ development GO:0050730 regulation of peptidyl-tyrosine phosphorylation GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0051052 regulation of DNA metabolic process GO:0051054 positive regulation of DNA metabolic process GO:0070661 leukocyte proliferation GO:0070662 mast cell proliferation GO:0070663 regulation of leukocyte proliferation GO:0070665 positive regulation of leukocyte proliferation GO:0070666 regulation of mast cell proliferation GO:0070668 positive regulation of mast cell proliferation GO:0097696 STAT cascade GO:1902105 regulation of leukocyte differentiation GO:1902107 positive regulation of leukocyte differentiation GO:1903706 regulation of hemopoiesis GO:1903708 positive regulation of hemopoiesis GO:1904892 regulation of STAT cascade GO:1904894 positive regulation of STAT cascade
Molecular Function	GO:0004713 protein tyrosine kinase activity GO:0005085 guanyl-nucleotide exchange factor activity GO:0005088 Ras guanyl-nucleotide exchange factor activity GO:0005125 cytokine activity GO:0005126 cytokine receptor binding GO:0005135 interleukin-3 receptor binding GO:0008083 growth factor activity GO:0070851 growth factor receptor binding
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 hsa04664 Fc epsilon RI signaling pathway
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
hsa04664 Fc epsilon RI signaling pathway

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	IL3
Name	interleukin 3
Aliases	IL-3; MULTI-CSF; MCGF; MGC79398; MGC79399; multilineage-colony-stimulating factor; hematopoietic growth fact ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IL3 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 IL3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
21078911	Colon Carcinoma	Promote immunity (T cell function)	In this tumoral environment, these monocytes can differentiate into tolerogenic dendritic cells (DCs) that produce IL-10 and potently induce regulatory T cell responses in vivo. Moreover, diverting the differentiation of Gr-1(+) monocytes into tolerogenic DCs by forced expression of IL-10 soluble receptor and IL-3 in tumor cells improves host immunosurveillance by reducing the regulatory T cell frequency and by inducing immunogenic DCs in the tumor.
27879269	Melanoma	Promote immunity (infiltration)	Therapeutic induction of basophilia by IL3/anti-IL3 antibody complexes, combined with transfer of CD8+ T cells, resulted in enhanced T-cell infiltration and tumor rejection.

Summary
Symbol	IL3
Name	interleukin 3
Aliases	IL-3; MULTI-CSF; MCGF; MGC79398; MGC79399; multilineage-colony-stimulating factor; hematopoietic growth fact ......
Chromosomal Location	5q31.1
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 IL3 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	IL3
Name	interleukin 3
Aliases	IL-3; MULTI-CSF; MCGF; MGC79398; MGC79399; multilineage-colony-stimulating factor; hematopoietic growth fact ......
Chromosomal Location	5q31.1
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 IL3 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	0.057	0.938
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.389	0.719
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.601	0.666
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	1
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	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.004	0.96

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of IL3 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	7.4	1.4	6	0.177
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	1.7	5.7	0.231
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	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	3.7	-3.7	0.415
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	7.1	-7.1	0.467
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	IL3
Name	interleukin 3
Aliases	IL-3; MULTI-CSF; MCGF; MGC79398; MGC79399; multilineage-colony-stimulating factor; hematopoietic growth fact ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IL3. 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	IL3
Name	interleukin 3
Aliases	IL-3; MULTI-CSF; MCGF; MGC79398; MGC79399; multilineage-colony-stimulating factor; hematopoietic growth fact ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IL3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IL3
Name	interleukin 3
Aliases	IL-3; MULTI-CSF; MCGF; MGC79398; MGC79399; multilineage-colony-stimulating factor; hematopoietic growth fact ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL3. 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	IL3
Name	interleukin 3
Aliases	IL-3; MULTI-CSF; MCGF; MGC79398; MGC79399; multilineage-colony-stimulating factor; hematopoietic growth fact ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IL3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IL3
Name	interleukin 3
Aliases	IL-3; MULTI-CSF; MCGF; MGC79398; MGC79399; multilineage-colony-stimulating factor; hematopoietic growth fact ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IL3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IL3
Name	interleukin 3
Aliases	IL-3; MULTI-CSF; MCGF; MGC79398; MGC79399; multilineage-colony-stimulating factor; hematopoietic growth fact ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IL3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting IL3.

ID	Name	Drug Type	Targets	#Targets
DB01025	Amlexanox	Small Molecule	FGF1, IL3, S100A12, S100A13	4
DB01593	Zinc	Small Molecule	A1BG, A2M, AGT, AHSG, ALDOA, APCS, APLP1, APLP2, APOA1, APOA2, APO ......	119
DB09221	Polaprezinc	Small Molecule	FLT1, HSP90AA1, HSP90AB1, IL3, IL6, NGF, PDGFRB, TNF	8

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