Browse IL4R

Summary
SymbolIL4R
Nameinterleukin 4 receptor
Aliases CD124; IL-4RAA; IL-4 receptor subunit alpha; IL4R nirs variant 1; interleukin-4 receptor alpha chain; CD ant ......
Chromosomal Location16p12.1-p11.2
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
 
Subcellular Location Cell membrane; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: Isoform 2: Secreted.
Domain PF09238 Interleukin-4 receptor alpha chain
Function

Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2. ; FUNCTION: Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells.

> Gene Ontology
 
Biological Process GO:0000768 syncytium formation by plasma membrane fusion
GO:0001562 response to protozoan
GO:0001819 positive regulation of cytokine production
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:0002285 lymphocyte activation involved in immune response
GO:0002286 T cell activation involved in immune response
GO:0002287 alpha-beta T cell activation involved in immune response
GO:0002292 T cell differentiation involved in immune response
GO:0002293 alpha-beta T cell differentiation involved in immune response
GO:0002294 CD4-positive, alpha-beta T cell differentiation 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:0002521 leukocyte differentiation
GO:0002532 production of molecular mediator involved in inflammatory response
GO:0002637 regulation of immunoglobulin production
GO:0002639 positive 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:0002696 positive 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:0002702 positive regulation of production of molecular mediator of immune response
GO:0002703 regulation of leukocyte mediated immunity
GO:0002705 positive regulation of leukocyte mediated immunity
GO:0002819 regulation of adaptive immune response
GO:0002820 negative regulation of adaptive immune response
GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002823 negative regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002825 regulation of T-helper 1 type immune response
GO:0002826 negative regulation of T-helper 1 type immune response
GO:0002828 regulation of type 2 immune response
GO:0002830 positive regulation of type 2 immune response
GO:0002886 regulation of myeloid leukocyte mediated immunity
GO:0002888 positive regulation of myeloid leukocyte mediated immunity
GO:0006887 exocytosis
GO:0006949 syncytium formation
GO:0007159 leukocyte cell-cell adhesion
GO:0007162 negative regulation of cell adhesion
GO:0007292 female gamete generation
GO:0007520 myoblast fusion
GO:0009306 protein secretion
GO:0010830 regulation of myotube differentiation
GO:0010831 positive regulation of myotube differentiation
GO:0014902 myotube differentiation
GO:0016064 immunoglobulin mediated immune response
GO:0017157 regulation of exocytosis
GO:0019724 B cell mediated immunity
GO:0022407 regulation of cell-cell adhesion
GO:0022408 negative regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030098 lymphocyte differentiation
GO:0030217 T cell differentiation
GO:0030728 ovulation
GO:0032386 regulation of intracellular transport
GO:0032388 positive regulation of intracellular transport
GO:0032418 lysosome localization
GO:0032602 chemokine production
GO:0032642 regulation of chemokine production
GO:0032722 positive regulation of chemokine production
GO:0033003 regulation of mast cell activation
GO:0033005 positive regulation of mast cell activation
GO:0033006 regulation of mast cell activation involved in immune response
GO:0033008 positive regulation of mast cell activation involved in immune response
GO:0035710 CD4-positive, alpha-beta T cell activation
GO:0035771 interleukin-4-mediated signaling pathway
GO:0042088 T-helper 1 type immune response
GO:0042092 type 2 immune response
GO:0042093 T-helper cell differentiation
GO:0042110 T cell activation
GO:0042116 macrophage activation
GO:0042692 muscle cell differentiation
GO:0042832 defense response to protozoan
GO:0043030 regulation of macrophage activation
GO:0043032 positive regulation of macrophage activation
GO:0043299 leukocyte degranulation
GO:0043300 regulation of leukocyte degranulation
GO:0043302 positive regulation of leukocyte degranulation
GO:0043303 mast cell degranulation
GO:0043304 regulation of mast cell degranulation
GO:0043306 positive regulation of mast cell degranulation
GO:0043367 CD4-positive, alpha-beta T cell differentiation
GO:0043370 regulation of CD4-positive, alpha-beta T cell differentiation
GO:0043371 negative regulation of CD4-positive, alpha-beta T cell differentiation
GO:0043372 positive regulation of CD4-positive, alpha-beta T cell differentiation
GO:0043627 response to estrogen
GO:0045055 regulated exocytosis
GO:0045063 T-helper 1 cell differentiation
GO:0045064 T-helper 2 cell differentiation
GO:0045576 mast cell activation
GO:0045580 regulation of T cell differentiation
GO:0045581 negative regulation of T cell differentiation
GO:0045582 positive regulation of T cell differentiation
GO:0045619 regulation of lymphocyte differentiation
GO:0045620 negative regulation of lymphocyte differentiation
GO:0045621 positive regulation of lymphocyte differentiation
GO:0045622 regulation of T-helper cell differentiation
GO:0045623 negative regulation of T-helper cell differentiation
GO:0045624 positive regulation of T-helper cell differentiation
GO:0045625 regulation of T-helper 1 cell differentiation
GO:0045626 negative regulation of T-helper 1 cell differentiation
GO:0045628 regulation of T-helper 2 cell differentiation
GO:0045630 positive regulation of T-helper 2 cell differentiation
GO:0045785 positive regulation of cell adhesion
GO:0045921 positive regulation of exocytosis
GO:0046631 alpha-beta T cell activation
GO:0046632 alpha-beta T cell differentiation
GO:0046634 regulation of alpha-beta T cell activation
GO:0046635 positive regulation of alpha-beta T cell activation
GO:0046636 negative regulation of alpha-beta T cell activation
GO:0046637 regulation of alpha-beta T cell differentiation
GO:0046638 positive regulation of alpha-beta T cell differentiation
GO:0046639 negative regulation of alpha-beta T cell differentiation
GO:0050663 cytokine secretion
GO:0050707 regulation of cytokine secretion
GO:0050708 regulation of protein secretion
GO:0050714 positive regulation of protein secretion
GO:0050715 positive regulation of cytokine secretion
GO:0050777 negative regulation of immune response
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050866 negative regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050868 negative regulation of T cell activation
GO:0050870 positive regulation of T cell activation
GO:0051047 positive regulation of secretion
GO:0051146 striated muscle cell differentiation
GO:0051147 regulation of muscle cell differentiation
GO:0051149 positive regulation of muscle cell differentiation
GO:0051153 regulation of striated muscle cell differentiation
GO:0051155 positive regulation of striated muscle cell differentiation
GO:0051222 positive regulation of protein transport
GO:0051249 regulation of lymphocyte activation
GO:0051250 negative regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051640 organelle localization
GO:0051656 establishment of organelle localization
GO:0060142 regulation of syncytium formation by plasma membrane fusion
GO:0060143 positive regulation of syncytium formation by plasma membrane fusion
GO:0060627 regulation of vesicle-mediated transport
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070670 response to interleukin-4
GO:0071353 cellular response to interleukin-4
GO:0071593 lymphocyte aggregation
GO:0090195 chemokine secretion
GO:0090196 regulation of chemokine secretion
GO:0090197 positive regulation of chemokine secretion
GO:0098542 defense response to other organism
GO:1901739 regulation of myoblast fusion
GO:1901741 positive regulation of myoblast fusion
GO:1902105 regulation of leukocyte differentiation
GO:1902106 negative regulation of leukocyte differentiation
GO:1902107 positive regulation of leukocyte differentiation
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903038 negative regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903305 regulation of regulated secretory pathway
GO:1903307 positive regulation of regulated secretory pathway
GO:1903532 positive regulation of secretion by cell
GO:1903706 regulation of hemopoiesis
GO:1903707 negative regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1904951 positive regulation of establishment of protein localization
GO:2000514 regulation of CD4-positive, alpha-beta T cell activation
GO:2000515 negative regulation of CD4-positive, alpha-beta T cell activation
GO:2000516 positive regulation of CD4-positive, alpha-beta T cell activation
Molecular Function GO:0004896 cytokine receptor activity
GO:0004913 interleukin-4 receptor activity
GO:0005057 receptor signaling protein activity
Cellular Component GO:0043235 receptor complex
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
hsa04151 PI3K-Akt signaling pathway
hsa04630 Jak-STAT signaling pathway
hsa04640 Hematopoietic cell lineage
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
SymbolIL4R
Nameinterleukin 4 receptor
Aliases CD124; IL-4RAA; IL-4 receptor subunit alpha; IL4R nirs variant 1; interleukin-4 receptor alpha chain; CD ant ......
Chromosomal Location16p12.1-p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between IL4R 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
 
  Literatures describing the relation between IL4R and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
24030977GliomaInhibit immunity (T cell function)Interleukin-4 receptor-α (IL-4Rα) mediates the immunosuppressive functions of myeloid cells, and polymorphisms in the IL-4Rα gene are associated with altered glioma risk and prognosis. In both mouse de novo gliomas and human glioblastoma cases, IL-4Rα was upregulated on glioma-infiltrating myeloid cells but not in the periphery or in normal brain. Mice genetically deficient for IL-4Rα exhibited a slower growth of glioma associated with reduced production in the glioma microenvironment of arginase, a marker of myeloid suppressor cells, which is critical for their T-cell inhibitory function.
21523763Pleural Malignant MesotheliomaInhibit immunityWithin MPM tumors, macrophages comprised 27% ± 9% of the tumor area and demonstrated an immunosuppressive phenotype with high expression of CD163, CD206, and interleukin-4 receptor α.
23271806Lung Carcinoma; MesotheliomaInhibit immunityRecurrent tumors and draining lymph nodes are infiltrated with M2 (CD11b+F4/80hiCD206hi and CD11b+F4/80hiCD124hi) macrophages and CD4+Foxp3+ regulatory T cells. This complex network of immunosuppression in the surrounding tumor microenvironment explains the resistance of tumor recurrences to conventional cancer vaccines despite small tumor size, an intact antitumor immune response, and unaltered cancer cells.
Summary
SymbolIL4R
Nameinterleukin 4 receptor
Aliases CD124; IL-4RAA; IL-4 receptor subunit alpha; IL4R nirs variant 1; interleukin-4 receptor alpha chain; CD ant ......
Chromosomal Location16p12.1-p11.2
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
  Statistical results of IL4R in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolIL4R
Nameinterleukin 4 receptor
Aliases CD124; IL-4RAA; IL-4 receptor subunit alpha; IL4R nirs variant 1; interleukin-4 receptor alpha chain; CD ant ......
Chromosomal Location16p12.1-p11.2
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
 
Points in the above scatter plot represent the expression difference of IL4R in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0170.969
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.1520.935
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0920.941
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.5250.229
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.830.751
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.140.966
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.5970.223
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.6810.635
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.4490.788
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.6220.699
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.9370.699
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.3140.00245
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of IL4R in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.15.91.21
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1031033.3-23.30.423
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolIL4R
Nameinterleukin 4 receptor
Aliases CD124; IL-4RAA; IL-4 receptor subunit alpha; IL4R nirs variant 1; interleukin-4 receptor alpha chain; CD ant ......
Chromosomal Location16p12.1-p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IL4R. 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
 
Summary
SymbolIL4R
Nameinterleukin 4 receptor
Aliases CD124; IL-4RAA; IL-4 receptor subunit alpha; IL4R nirs variant 1; interleukin-4 receptor alpha chain; CD ant ......
Chromosomal Location16p12.1-p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IL4R. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL4R.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolIL4R
Nameinterleukin 4 receptor
Aliases CD124; IL-4RAA; IL-4 receptor subunit alpha; IL4R nirs variant 1; interleukin-4 receptor alpha chain; CD ant ......
Chromosomal Location16p12.1-p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL4R. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolIL4R
Nameinterleukin 4 receptor
Aliases CD124; IL-4RAA; IL-4 receptor subunit alpha; IL4R nirs variant 1; interleukin-4 receptor alpha chain; CD ant ......
Chromosomal Location16p12.1-p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of IL4R expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolIL4R
Nameinterleukin 4 receptor
Aliases CD124; IL-4RAA; IL-4 receptor subunit alpha; IL4R nirs variant 1; interleukin-4 receptor alpha chain; CD ant ......
Chromosomal Location16p12.1-p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between IL4R and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolIL4R
Nameinterleukin 4 receptor
Aliases CD124; IL-4RAA; IL-4 receptor subunit alpha; IL4R nirs variant 1; interleukin-4 receptor alpha chain; CD ant ......
Chromosomal Location16p12.1-p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting IL4R collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting IL4R.
ID Name Drug Type Targets #Targets
DB05078AER001Small MoleculeIL13RA2, IL4R2
DB12159DupilumabBiotechIL4R1