IL4R Gene

IL4R stands for "Interleukin 4 Receptor" ). The IL4R gene is a protein-coding gene located on chromosome 16p12.1. It encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind both the cytokine interleukin-4 and the cytokine interleukin-13 to regulate IgE production. Coupling to the receptor protein activates the JAK1/2/3-STAT6 signaling pathway.

Furthermore, IL4/IL13 responses are involved in the regulation of IgE production as well as chemokine and mucus production at sites of allergic inflammation. In certain cell types, they can signal by activating insulin receptor substrates, IRS1/IRS2. A soluble form of the encoded interleukin 4 receptor can be produced by proteolysis of the membrane-bound protein. This soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T cells.

Allelic variations in the IL4R gene are associated with atopic diseases (e.g. allergic rhinitis, sinusitis, allergic bronchial asthma, atopic dermatitis). Polymorphisms in this gene are also associated with resistance to human immunodeficiency virus type 1 infection.

Glioma/astrocytoma: Polymorphisms in the IL4R gene may be associated with glioma risk. Studies suggest that the IL4R rs1801275 GG genotype increases the risk of death in glioma and astrocytoma patients (Jin TB et al 2016).

MS risk: The "rs2243250 (C/T) polymorphism" in the IL4R gene may reduce MS risk in the Caucasian population, while the IL4 I3(709)*VNTR and IL4R rs1801275 polymorphisms are not associated with MS risk in the Caucasian population (Zhang Z et al. 2016).

Primary mediastinal large B-cell lymphoma: In primary mediastinal large B-cell lymphoma (PMBCL), a subtype of diffuse large B-cell lymphoma, animal experiments demonstrated that expression of an IL4R mutant (I242N) resulted in a growth advantage in vivo (Viganò E et al. 2018).

Oncologics: In clinical oncology studies with recombinant immunotoxins, IL-4 and IL-13 receptors are promising target genes.

1. Jin TB et al. (2016) Polymorphism in the IL4R gene and clinical features are associated with glioma prognosis: analyses of case-cohort studies. Medicine (Baltimore) 95: e4231
2. Suzuki A et al (2015) Targeting of IL-4 and IL-13 receptors for cancer therapy. Cytokine 75:79-88.
3. Tavakolpour S (2016) Interleukin 7 receptor polymorphisms and the risk of multiple sclerosis: A meta-analysis. Mult Scler Relat Disord 8:66-73.
4. Viganò E et al. (2018) Somatic IL4R mutations in primary mediastinal large B-cell lymphoma lead to constitutive JAK-STAT signaling activation. Blood131:2036-2046.
5. Zhang Z et al. (2016) Association of IL4 and IL4R polymorphisms with multiple sclerosis susceptibility in Caucasian population: A meta-analysis. J Neurol Sci 363:107-113.