IL4 interleukin 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: IL4provided by HGNC
Official Full Name: interleukin 4provided by HGNC
Primary source: HGNC:HGNC:6014
See related: Ensembl:ENSG00000113520 MIM:147780; AllianceGenome:HGNC:6014
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: BSF1; IL-4; BCGF1; BSF-1; BCGF-1
Summary: The protein encoded by this gene is a pleiotropic cytokine produced by activated T cells. This cytokine is a ligand for interleukin 4 receptor. The interleukin 4 receptor also binds to IL13, which may contribute to many overlapping functions of this cytokine and IL13. STAT6, a signal transducer and activator of transcription, has been shown to play a central role in mediating the immune regulatory signal of this cytokine. This gene, IL3, IL5, IL13, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL13. This gene, IL13 and IL5 are found to be regulated coordinately by several long-range regulatory elements in an over 120 kilobase range on the chromosome. IL4 is considered an important cytokine for tissue repair, counterbalancing the effects of proinflammatory type 1 cytokines, however, it also promotes allergic airway inflammation. Moreover, IL-4, a type 2 cytokine, mediates and regulates a variety of human host responses such as allergic, anti-parasitic, wound healing, and acute inflammation. This cytokine has been reported to promote resolution of neutrophil-mediated acute lung injury. In an allergic response, IL-4 has an essential role in the production of allergen-specific immunoglobin (Ig) E. This pro-inflammatory cytokine has been observed to be increased in COVID-19 (Coronavirus disease 2019) patients, but is not necessarily associated with severe COVID-19 pathology. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Aug 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for disease process.
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 5q31.1

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (132673989..132682678)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (133193788..133202478)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (132009681..132018370)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Association of NLRP3 and IL-4 VNTR polymorphisms and genetic susceptibility to preeclampsia: A case-control study.
Title: Association of NLRP3 and IL-4 VNTR polymorphisms and genetic susceptibility to preeclampsia: A case-control study.
Nasal mucosal fibroblasts produce IL-4 to induce Th2 response.
Title: Nasal mucosal fibroblasts produce IL-4 to induce Th2 response.
The aryl hydrocarbon receptor shapes monocyte transcriptional responses to interleukin-4 by prolonging STAT6 binding to promoters.
Title: The aryl hydrocarbon receptor shapes monocyte transcriptional responses to interleukin-4 by prolonging STAT6 binding to promoters.
A call for clinical trials in glioblastoma multiforme for interleukin 4, interleukin 6, interleukin 13 and CD40.
Title: A call for clinical trials in glioblastoma multiforme for interleukin 4, interleukin 6, interleukin 13 and CD40.
Increased level of GATA3-AS1 long non-coding RNA is correlated with the upregulation of GATA3 and IL-4 genes in multiple sclerosis patients.
Title: Increased level of GATA3-AS1 long non-coding RNA is correlated with the upregulation of GATA3 and IL-4 genes in multiple sclerosis patients.
PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus.
Title: PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus.
Association of IL-4 polymorphism with severe periodontitis in a sample of Iraqi population.
Title: Association of IL-4 polymorphism with severe periodontitis in a sample of Iraqi population.
IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4.
Title: IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4.
The association of 25(OH)D, interleukin-4, interleukin-5, and interleukin-13 levels with the burden of soil-transmitted helminth infection in stunted children aged 24-59 months.
Title: The association of 25(OH)D, interleukin-4, interleukin-5, and interleukin-13 levels with the burden of soil-transmitted helminth infection in stunted children aged 24-59 months.
Interleukin-4 and Interleukin-17 are associated with coronary artery disease.
Title: Interleukin-4 and Interleukin-17 are associated with coronary artery disease.

Submit: New GeneRIF Correction See all GeneRIFs (928)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 replication in resting peripheral blood CD4 T cells is rescued by IL4; IL4 rescues resting peripheral blood CD4 T cells from HIV-1-induced T cell death	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 induces release of IL-4 in CD4+ T cells	PubMed
	env	HIV-1 gp120 cooperates with BAFF and cytokines IL-4 and IL-10 to activate mannose C-type lectin receptors-expressing B cells	PubMed
	env	HIV-1 gp120 upregulates IL-4-induced IgE production through the regulation of the nitric oxide pathway	PubMed
	env	Molecular interactions of CD2 with LFA-3 and CD28 with B7-1 in conjunction with TCR occupancy prevent T cells from programmed apoptosis mediated by binding of CD4 to HIV-1 gp120, resulting in increased levels of IL-2 and IL-4 secretion from the T cells	PubMed
	env	Antigen-induced interleukin 4 secretion is markedly reduced in HIV-1 gp120-treated T cells	PubMed
Envelope surface glycoprotein gp160, precursor	env	Pretreatment of CD4+ cells with HIV-1 gp160 significantly reduces PHA-induced secretion of IFN-gamma and IL-2 but augments IL-4 production	PubMed
Nef	nef	HIV-1 Nef suppresses immunoglobulin class-switch DNA recombination by inducing IkappaBalpha and SOCS proteins, which block CD154, IL-4 and IL-10 cytokine signaling via NF-kappaB and STAT transcription factors	PubMed
Tat	tat	HIV-1 Tat significantly decreases TNF-alpha and IL-6 secretion but increases IL-4 levels in human hepatocellular carcinoma cells	PubMed
	tat	Monocytes treated with HIV-1 clade C Tat show significant upregulation of anti-inflammatory cytokines, IL-4 and IL-10, as compared to clade B Tat-treated cultures	PubMed
	tat	Activation of IL-4/STAT6 signaling partially contributes to HIV-1 Tat-induced Kaposi's sarcoma-associated herpes virus (KSHV) replication	PubMed
	tat	HIV-1 Tat upregulates IL-4 expression in Jurkat T-cells	PubMed
	tat	HIV-1 Tat induces IL-4 and IL-13 release from basophils, leading to dysregulation of the IgE/Fc epsilon RI network	PubMed
Vif	vif	HIV-1 Vif upregulates the expression of interleukin 4 (IL4) in Vif-expression T cells	PubMed
Vpr	vpr	HIV-1 Vpr suppresses expression of IL-4 through suppression of NF-kappa B activity via the induction of I kappa B alpha	PubMed
integrase	gag-pol	Treatment of resting CD4+ T cells with cytokines IL-2, IL-4, IL-7, or IL15 enhances HIV-1 IN mutant D116N to generate de novo virus production	PubMed
matrix	gag	HIV-1 Matrix slightly enhances TNF-alpha and IFN-gamma secretion induced by IL-15 monocyte stimulation and counteracts IL-4 mediated inhibition of the production of these cytokines	PubMed
	gag	HIV-1 Matrix blocks IL-4 downregulation of interferon gamma and TNF-alpha	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

REN71232 (e-PCR)
- UniSTS:396032

REN71233 (e-PCR)
- UniSTS:396033

REN71234 (e-PCR)
- UniSTS:396034

ECD00749 (e-PCR)
- UniSTS:281858

REN71235 (e-PCR)
- UniSTS:396035

REN71236 (e-PCR)
- UniSTS:396036

REN71237 (e-PCR)
- UniSTS:396037

REN71238 (e-PCR)
- UniSTS:396038

REN71239 (e-PCR)
- UniSTS:396039

REN71240 (e-PCR)
- UniSTS:396040

REN71241 (e-PCR)
- UniSTS:396041

REN71242 (e-PCR)
- UniSTS:396042

REN71243 (e-PCR)
- UniSTS:396043

REN71244 (e-PCR)
- UniSTS:396044

REN71245 (e-PCR)
- UniSTS:396045

REN71246 (e-PCR)
- UniSTS:396046

REN71247 (e-PCR)
- UniSTS:396047

REN71248 (e-PCR)
- UniSTS:396048

REN71249 (e-PCR)
- UniSTS:396049

REN71250 (e-PCR)
- UniSTS:396050

REN71251 (e-PCR)
- UniSTS:396051

REN71252 (e-PCR)
- UniSTS:396052

REN71253 (e-PCR)
- UniSTS:396053

REN71254 (e-PCR)
- UniSTS:396054

REN71255 (e-PCR)
- UniSTS:396055

REN71256 (e-PCR)
- UniSTS:396056

REN71257 (e-PCR)
- UniSTS:396057

REN71258 (e-PCR)
- UniSTS:396058

REN71259 (e-PCR)
- UniSTS:396059

REN71260 (e-PCR)
- UniSTS:396060

REN71261 (e-PCR)
- UniSTS:396061

REN71262 (e-PCR)
- UniSTS:396062

REN71263 (e-PCR)
- UniSTS:396063

REN71264 (e-PCR)
- UniSTS:396064

REN71265 (e-PCR)
- UniSTS:396065

ECD12380 (e-PCR)
- UniSTS:293413

GDB:456299 (e-PCR)
- UniSTS:157483

ECD22217 (e-PCR)
- UniSTS:303205

ECD07045 (e-PCR)
- UniSTS:288103

ECD20165 (e-PCR)
- UniSTS:301169

ECD08604 (e-PCR)
- UniSTS:289652

PMC356970P2 (e-PCR)
- UniSTS:273284

GDB:180247 (e-PCR)
- UniSTS:155063

GDB:180248 (e-PCR)
- UniSTS:155064

GDB:207332 (e-PCR)
- UniSTS:156119

ECD19759 (e-PCR)
- UniSTS:300763

ECD02519 (e-PCR)
- UniSTS:283616

PMC324417P1 (e-PCR)
- UniSTS:273131

ECD01760 (e-PCR)
- UniSTS:282861

REN71218 (e-PCR)
- UniSTS:396018

REN71219 (e-PCR)
- UniSTS:396019

REN71220 (e-PCR)
- UniSTS:396020

REN71221 (e-PCR)
- UniSTS:396021

REN71222 (e-PCR)
- UniSTS:396022

REN71223 (e-PCR)
- UniSTS:396023

ECD08735 (e-PCR)
- UniSTS:289783

REN71224 (e-PCR)
- UniSTS:396024

REN71225 (e-PCR)
- UniSTS:396025

REN71226 (e-PCR)
- UniSTS:396026

REN71227 (e-PCR)
- UniSTS:396027

REN71228 (e-PCR)
- UniSTS:396028

REN71229 (e-PCR)
- UniSTS:396029

REN71230 (e-PCR)
- UniSTS:396030

REN71231 (e-PCR)
- UniSTS:396031

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IDA Inferred from Direct Assay more info	PubMed
enables growth factor activity	NAS Non-traceable Author Statement more info	PubMed
enables interleukin-4 receptor binding	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell differentiation	TAS Traceable Author Statement more info	PubMed
involved_in T cell activation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cell surface receptor signaling pathway via JAK-STAT	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cholesterol metabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in dendritic cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in interleukin-4-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in interleukin-4-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in macrophage activation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in myeloid dendritic cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cellular response to transforming growth factor beta stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of complement-dependent cytotoxicity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of endothelial cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of epithelial cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of inflammatory response	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of neuroinflammatory response	IC Inferred by Curator more info
involved_in negative regulation of osteoclast differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuroinflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of ATP biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of B cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of DNA-templated transcription	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MHC class II biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of T cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of T-helper 2 cell cytokine production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of amyloid-beta clearance	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of cell migration	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of cellular respiration	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-10 production	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of interleukin-13 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of isotype switching to IgE isotypes	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of isotype switching to IgG isotypes	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of macroautophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of receptor-mediated endocytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of isotype switching	TAS Traceable Author Statement more info	PubMed
involved_in regulation of phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in type 2 immune response	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: interleukin-4

Names: B cell growth factor 1; B_cell stimulatory factor 1; binetrakin; lymphocyte stimulatory factor 1; pitrakinra

NCBI Reference Sequences (RefSeq)

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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_023252.1 RefSeqGene

Range

5309..13998

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000589.4 → NP_000580.1 interleukin-4 isoform 1 precursor

See identical proteins and their annotated locations for NP_000580.1

Status: REVIEWED

Description

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

Source sequence(s)

BC067514, CD640452, M13982

Consensus CDS

CCDS4158.1

UniProtKB/Swiss-Prot

P05112, Q14630, Q6NZ77

UniProtKB/TrEMBL

B0JFA2, D4HNR6

Related

ENSP00000231449.2, ENST00000231449.7

Conserved Domains (1) summary

pfam00727
Location:28 → 149

IL4; Interleukin 4
NM_001354990.2 → NP_001341919.1 interleukin-4 isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate exon compared to variant 1, that causes a frameshift. The resulting isoform (3) has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

AC004039, JX878389

Consensus CDS

CCDS87322.1

UniProtKB/TrEMBL

U3LVN1

Related

ENSP00000480581.1, ENST00000622422.1

Conserved Domains (1) summary

cl11518
Location:1 → 77

IL4; Interleukin 4
NM_172348.3 → NP_758858.1 interleukin-4 isoform 2 precursor

See identical proteins and their annotated locations for NP_758858.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the 5' region, compared to variant 1, resulting an isoform (2) that lacks an internal region, as compared to isoform 1.

Source sequence(s)

AB102862, BC067514, CD640452, M13982

Consensus CDS

CCDS4159.1

UniProtKB/TrEMBL

Q5FC01, Q9UPB9

Related

ENSP00000325190.3, ENST00000350025.2

Conserved Domains (1) summary

pfam00727
Location:28 → 133

IL4; Interleukin 4