IL4R interleukin 4 receptor [Homo sapiens] - Gene

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Summary

Official Symbol: IL4Rprovided by HGNC
Official Full Name: interleukin 4 receptorprovided by HGNC
Primary source: HGNC:6015
Locus tag: 582J2.1
See related: Ensembl:ENSG00000077238; HPRD:00990; MIM:147781; Vega:OTTHUMG00000097015
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CD124; IL4RA; IL-4RA
Summary: This gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind interleukin 4 and interleukin 13 to regulate IgE production. The encoded protein also can bind interleukin 4 to promote differentiation of Th2 cells. A soluble form of the encoded protein can be produced by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitus, asthma, or eczema. Polymorphisms in this gene are also associated with resistance to human immunodeficiency virus type-1 infection. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

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Genomic context

Location :: 16p12.1-p11.2

Sequence :: Chromosome: 16; NC_000016.9 (27325251..27376099)

See IL4R in Epigenomics, MapViewer

Chromosome 16 - NC_000016.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

IL-4Ralpha polymorphisms were associated with susceptibility to rheumatoid arthritis and may be helpful in early detection of erosive rheumatoid arthritis.
Title: Association of interleukin-4 receptor gene polymorphisms with rheumatoid arthritis in Egyptian female patients.
there was no significant association of the IL13 and IL4RA polymorphisms with mite-sensitized persistent allergic rhinitis
Title: Association study on IL4, IL13 and IL4RA polymorphisms in mite-sensitized persistent allergic rhinitis in a Chinese population.
Data showed that polymorphisms in IL4, IL13, and their receptors do not play a role in SSc and do not influence the expression of their corresponding transcript in peripheral blood cells.
Title: Polymorphisms in the interleukin 4, interleukin 13, and corresponding receptor genes are not associated with systemic sclerosis and do not influence gene expression.
In Korean asthmatic children, increased serum IgE level was a multi-locus interaction between IL-4Ralpha, IL-13, IL-13Ralpha1, CD14, and CTLA4 polymorphisms. The combination of CTLA4/IL-13 and IL-13/IL-13Ralpha1 polymorphisms showed strong synergistic ...
Title: Gene-gene interactions between candidate gene polymorphisms are associated with total IgE levels in Korean children with asthma.
The Q551R IL-4RA polymorphism is a putative risk indicator for severe chronic periodontitis, but was not significant associated to AP.
Title: The genetic impact of the Q551R interleukin-4 receptor alpha polymorphism for aggressive or chronic periodontitis and the occurrence of periodontopathic bacteria.
The data provide evidence for codiffusion of IL-4-A647 bound IL-4Ralpha and the type II subunit IL-13Ralpha1 fused to enhanced green fluorescent protein.
Title: Single cell analysis of ligand binding and complex formation of interleukin-4 receptor subunits.
did not identify any SNPs in the IL-4, IL-4R and IL-13Ralpha2 genes that were associated with atopic dermatitis
Title: Association of polymorphisms in genes encoding IL-4, IL-13 and their receptors with atopic dermatitis in a Korean population.
Transfectants expressing the single nucleotide polymorphism in FCER2 exhibited increased IL-4Ralpha expression after stimulation through CD23 compared with wild-type.
Title: Asthma-related SNP in FCER2 is associated with increased expression of IL-4R on human B cells.
Studies indicate that RAD50 and PTPRE of crude associations with asthma at a Bonferroni-corrected level of significance, while IL4R, CCL5 and TBXA2R of nominal significance.
Title: Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma.
IL-4RA Q576R polymorphisms impart a modest yet significant risk for asthma.
Title: [Meta-analysis on interleukin-4 receptor α chain Q576R gene polymorphisms and bronchial asthma susceptibility].

Submit: New GeneRIF Correction See all (104)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat upregulates IL-4R in the Raji B-lymphoblastoid cell line, suggesting the possibility that the immunosuppressive effects of HIV-1 are mediated at least in part through IL-4 receptors	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_000409.1	NP_006089.1	GNB2L1	BIND	PubMed	IL-4R-alpha interacts with RACK-1. This interaction was modelled on a demonstrated interaction between IL-4R-alpha from an unspecified species and human RACK-1.
NP_000409.1	NP_000580.1	IL4	BIND	PubMed	IL4R Interacts with IL4.
NP_000409.1	NP_000580.1	IL4	BIND	PubMed	IL4R -alpha(PDB ID: 1IAR_B) interacts with IL4(PDB ID: 1IAR_A).
NP_000409.1	NP_002218.1	JAK1	BIND	PubMed	JAK1 interacts with IL4R-alpha.
NP_000409.1	NP_003144.3	STAT6	BIND	PubMed	IL-4 receptor-alpha interacts with STAT 6.
P24394	O95376	ARIH2	HPRD	PubMed
P24394	P25942	CD40	HPRD	PubMed
P24394	O60496	DOK2	HPRD	PubMed
P24394	P07332	FES	HPRD	PubMed
P24394	P63244	GNB2L1	HPRD	PubMed
P24394	P35225	IL13	HPRD	PubMed
P24394	P78552	IL13RA1	HPRD	PubMed
P24394	P31785	IL2RG	HPRD	PubMed
P24394	P05112	IL4	HPRD	PubMed
P24394	O00145	INPP5D	HPRD	PubMed
P24394	P35568	IRS1	HPRD	PubMed
P24394	Q9Y4H2	IRS2	HPRD	PubMed
P24394	P23458	JAK1	HPRD	PubMed
P24394	O60674	JAK2	HPRD	PubMed
P24394	P52333	JAK3	HPRD	PubMed
P24394	P14598	NCF1	HPRD	PubMed
P24394	Q05513	PRKCZ	HPRD	PubMed
P24394	Q06124	PTPN11	HPRD	PubMed
P24394	P29350	PTPN6	HPRD	PubMed
P24394	P29353	SHC1	HPRD	PubMed
P24394	O75159	SOCS5	HPRD	PubMed
P24394	P42226	STAT6	HPRD	PubMed
BioGRID:109780	BioGRID:115694	ARIH2	BioGRID	PubMed	Two-hybrid
BioGRID:109780	BioGRID:115671	GNB2L1	BioGRID	PubMed	Reconstituted Complex
BioGRID:109780	BioGRID:114593	HGS	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:109780	BioGRID:109779	IL4	BioGRID	PubMed	Co-crystal Structure
BioGRID:109780	BioGRID:109847	INPP5D	BioGRID	PubMed	Reconstituted Complex
BioGRID:109780	BioGRID:109919	JAK1	BioGRID	PubMed	Reconstituted Complex
BioGRID:109780	BioGRID:575724	NCF1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109780	BioGRID:111745	PTPN11	BioGRID	PubMed	Reconstituted Complex
BioGRID:109780	BioGRID:111742	PTPN6	BioGRID	PubMed	Reconstituted Complex
BioGRID:109780	BioGRID:112361	SHC1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:109780	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western

Function	Evidence Code	Pubs
insulin receptor substrate binding	RCA inferred from Reviewed Computational Analysis more info	PubMed
interleukin-4 receptor activity	TAS Traceable Author Statement more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
receptor activity	IEA Inferred from Electronic Annotation more info
receptor signaling protein activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
immune response	TAS Traceable Author Statement more info	PubMed
interleukin-4-mediated signaling pathway	TAS Traceable Author Statement more info	PubMed
negative regulation of T-helper 1 cell differentiation	IEA Inferred from Electronic Annotation more info
ovulation	IEA Inferred from Electronic Annotation more info
positive regulation of T-helper 2 cell differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of chemokine secretion	IEA Inferred from Electronic Annotation more info
positive regulation of macrophage activation	IEA Inferred from Electronic Annotation more info
production of molecular mediator involved in inflammatory response	IEA Inferred from Electronic Annotation more info
regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
response to estrogen stimulus	IEA Inferred from Electronic Annotation more info
signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
extracellular region	IEA Inferred from Electronic Annotation more info
extracellular space	IEA Inferred from Electronic Annotation more info
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: interleukin-4 receptor subunit alpha

Names: interleukin-4 receptor subunit alpha; IL-4 receptor subunit alpha; interleukin-4 receptor alpha chain

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012086.1 RefSeqGene

Range

4980..55849

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000418.3 → NP_000409.1 interleukin-4 receptor subunit alpha isoform a precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

BC110343, DA492909, X52425

Consensus CDS

CCDS10629.1

UniProtKB/Swiss-Prot

P24394

Related

ENSP00000379111, OTTHUMP00000122506, ENST00000395762, OTTHUMT00000214104

Conserved Domains (2) summary

cd00063
Location:123 – 219
Blast Score: 105

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam09238
Location:27 – 121
Blast Score: 426

IL4Ra_N; Interleukin-4 receptor alpha chain, N-terminal
NM_001257406.1 → NP_001244335.1 interleukin-4 receptor subunit alpha isoform a precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Both variants 1 and 3 encode the same isoform (a).

Source sequence(s)

AC106739, AK314863, BC110343, DA492909

Conserved Domains (2) summary

cd00063
Location:123 – 219
Blast Score: 105

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam09238
Location:27 – 121
Blast Score: 426

IL4Ra_N; Interleukin-4 receptor alpha chain, N-terminal
NM_001257407.1 → NP_001244336.1 interleukin-4 receptor subunit alpha isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (c) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AK303255, BC110343, DA492909, X52425

Conserved Domains (2) summary

cd00063
Location:108 – 204
Blast Score: 105

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam09238
Location:12 – 106
Blast Score: 428

IL4Ra_N; Interleukin-4 receptor alpha chain, N-terminal
NM_001257997.1 → NP_001244926.1 interleukin-4 receptor subunit alpha isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR, uses an alternate splice site in the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (d) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AC106739, BC110343, DA492909

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000016.9 Reference GRCh37.p5 Primary Assembly

Range

27325251..27376099

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000148.1 Alternate HuRef

Range

25413559..25464524

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001008699.1: Suppressed sequence

Description

NM_001008699.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC004525.1	AAC23495.1
genomic	AC106739.5 (302..51150)	None
genomic	AF421855.1	AAL12163.1
genomic	AJ293647.1	CAC20445.1
genomic	AJ293648.1	CAC20446.1
genomic	AJ293649.1	CAC20447.1
genomic	AJ293650.1	CAC20448.1
genomic	AJ293651.1	CAC20449.1
genomic	AJ293652.1	CAC20450.1
genomic	AJ293653.1	CAC20451.1
genomic	AJ293654.1	CAC20452.1
genomic	CH471145.2	EAW55750.1
genomic	CS104810.1	CAJ01243.1
mRNA	AA838318.1	None
mRNA	AK223591.1	BAD97311.1
mRNA	AK303255.1	BAG64338.1
mRNA	AK314863.1	BAG37378.1
mRNA	BC110343.1	None
mRNA	BC136365.1	AAI36366.1
mRNA	BC151131.1	AAI51132.1
mRNA	BX479288.1	None
mRNA	DA492909.1	None
mRNA	EF173858.1	ABM53131.1
mRNA	X52425.1	CAA36672.1