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Interleukin-4 receptor subunit α

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1697

Nomenclature: Interleukin-4 receptor subunit α

Family: IL-2 receptor family

Contents:

Quaternary Structure: Complexes
Interleukin-4 receptor type I
Interleukin-4 receptor type II
Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 825 16p12.1 IL4R interleukin 4 receptor
Mouse 1 810 7 68.94 cM Il4ra interleukin 4 receptor, alpha
Rat 1 801 1q36 Il4r interleukin 4 receptor
Previous and Unofficial Names Click here for help
CD124 | IL-4 receptor alpha chain | interleukin 4 receptor, alpha
Database Links Click here for help
Alphafold P24394 (Hs), P16382 (Mm), Q63257 (Rn)
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL3580490 (Hs)
Ensembl Gene ENSG00000077238 (Hs), ENSMUSG00000030748 (Mm), ENSRNOG00000015441 (Rn)
Entrez Gene 3566 (Hs), 16190 (Mm), 25084 (Rn)
Human Protein Atlas ENSG00000077238 (Hs)
KEGG Gene hsa:3566 (Hs), mmu:16190 (Mm), rno:25084 (Rn)
OMIM 147781 (Hs)
Pharos P24394 (Hs)
UniProtKB P24394 (Hs), P16382 (Mm), Q63257 (Rn)
Wikipedia IL4R (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
stapokibart Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Binding 9.6 pKd 2
⤷ pKd 9.6 (Kd 2.5x10-10 M) [2]
Description: Binding affinity determined by SPR
stapokibart Peptide Approved drug Immunopharmacology Ligand Monkey Binding 8.8 pKd 2
⤷ pKd 8.8 (Kd 1.5x10-9 M) [2]
Description: Binding affinity determined by SPR
stapokibart Peptide Approved drug Immunopharmacology Ligand Rn Binding 8.6 pKd 2
⤷ pKd 8.6 (Kd 2.75x10-9 M) [2]
Description: Binding affinity determined by SPR
dupilumab Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Binding 11.1 pIC50 3
⤷ pIC50 11.1 (IC50 8.8x10-12 M) [3]
Description: Value derived from an ELISA-based solution competition assay.
stapokibart Peptide Approved drug Immunopharmacology Ligand Hs Antagonist 9.4 pIC50 2
⤷ pIC50 9.4 (IC50 4x10-10 M) [2]
Description: Antagonism of IL-4 interaction with IL-4R&alpha determined by competitive ELISA
ligufalimab Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Binding - - 4
⤷ [4]
Immunopharmacology Comments
IL4R is the common ligand binding subunit shared by the IL-4 receptors type I (receptor for IL-4) and type II (receptor for IL-4 and IL-13). A gain-of-function mutation in IL4R has been associated with atopy, enhanced B cell isotype switching from mu to epsilon and therefore elevated IgE levels [1]. This subunit is the molecular target of the investigational monoclonal antibody dupilumab, that is in clinical trial as a therapy for atopic allergic conditions and nasal polyposis.
Immuno Process Associations
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 3 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0016064 immunoglobulin mediated immune response IEA
GO:0045063 T-helper 1 cell differentiation IEA
GO:0045626 negative regulation of T-helper 1 cell differentiation IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 6 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0043032 positive regulation of macrophage activation IEA
GO:0043306 positive regulation of mast cell degranulation IEA
GO:0045063 T-helper 1 cell differentiation IEA
GO:0045064 T-helper 2 cell differentiation IEA
GO:0045626 negative regulation of T-helper 1 cell differentiation IEA
GO:0045630 positive regulation of T-helper 2 cell differentiation IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 3 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0032722 positive regulation of chemokine production IEA
GO:0045626 negative regulation of T-helper 1 cell differentiation IEA
GO:0045630 positive regulation of T-helper 2 cell differentiation IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 5 GO processes, IEA only
GO:0004896 cytokine receptor activity IBA
GO:0004913 interleukin-4 receptor activity IDA
GO:0019221 cytokine-mediated signaling pathway IBA
GO:0035771 interleukin-4-mediated signaling pathway IDA
click arrow to show/hide IEA associations
GO:0032722 positive regulation of chemokine production IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 5 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002639 positive regulation of immunoglobulin production IEA
GO:0043032 positive regulation of macrophage activation IEA
GO:0043306 positive regulation of mast cell degranulation IEA
GO:0045626 negative regulation of T-helper 1 cell differentiation IEA
GO:0045630 positive regulation of T-helper 2 cell differentiation IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 4 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0045063 T-helper 1 cell differentiation IEA
GO:0045064 T-helper 2 cell differentiation IEA
GO:0045626 negative regulation of T-helper 1 cell differentiation IEA
GO:0045630 positive regulation of T-helper 2 cell differentiation IEA
Immuno Process:  Inflammation
GO Annotations:  Associated to 7 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002532 production of molecular mediator involved in inflammatory response IEA
GO:0043032 positive regulation of macrophage activation IEA
GO:0043306 positive regulation of mast cell degranulation IEA
GO:0045063 T-helper 1 cell differentiation IEA
GO:0045064 T-helper 2 cell differentiation IEA
GO:0045626 negative regulation of T-helper 1 cell differentiation IEA
GO:0045630 positive regulation of T-helper 2 cell differentiation IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 5 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0016064 immunoglobulin mediated immune response IEA
GO:0045063 T-helper 1 cell differentiation IEA
GO:0045064 T-helper 2 cell differentiation IEA
GO:0045626 negative regulation of T-helper 1 cell differentiation IEA
GO:0045630 positive regulation of T-helper 2 cell differentiation IEA
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Human immunodeficiency virus type 1, susceptibility to
Synonyms: Human immunodeficiency virus infectious disease [Disease Ontology: DOID:526]
Disease Ontology: DOID:526
OMIM: 609423
Orphanet: ORPHA319269
Role:  A polymorphism in IL4R (I50V) is associated with slower progression to AIDs in HIV-positive individuals.
References:  5
Disease:  IgE responsiveness, atopic; IGER
OMIM: 147050

References

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1. Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA. (1997) The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N Engl J Med, 337 (24): 1720-5. [PMID:9392697]

2. Liu W, Zhao Y, He Y, Yan X, Yu J, Song Q, Zhang L, Dong B, Xu G, Wang C et al.. (2024) Stapokibart (CM310) targets IL-4Rα for the treatment of type 2 inflammation. iScience, 27 (9): 110721. [PMID:39262798]

3. Martin JH, Huang TT, Fairhurst JL, Papadopoulos NJ. (2009) Cytokine specific immunoglobulin for use in diagnosis, prevention and treatment ,of cell proliferative, inflammatory, allergic, respiratory, autoimmune and arthritic disorders. Patent number: US7608693. Assignee: Regeneron Pharmaceuticals, Inc.. Priority date: 02/10/2006. Publication date: 27/10/2009.

4. Qu T, Zhong T, Pang X, Huang Z, Jin C, Wang ZM, Li B, Xia Y. (2022) Ligufalimab, a novel anti-CD47 antibody with no hemagglutination demonstrates both monotherapy and combo antitumor activity. J Immunother Cancer, 10 (11). [PMID:36450383]

5. Soriano A, Lozano F, Oliva H, García F, Nomdedéu M, De Lazzari E, Rodríguez C, Barrasa A, Lorenzo JI, Del Romero J et al.. (2005) Polymorphisms in the interleukin-4 receptor alpha chain gene influence susceptibility to HIV-1 infection and its progression to AIDS. Immunogenetics, 57 (9): 644-54. [PMID:16189667]

How to cite this page

IL-2 receptor family: Interleukin-4 receptor subunit α. Last modified on 06/05/2025. Accessed on 21/06/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1697.