IL18 interleukin 18 [Homo sapiens (human)] - Gene

Summary

Official Symbol: IL18provided by HGNC
Official Full Name: interleukin 18provided by HGNC
Primary source: HGNC:HGNC:5986
See related: Ensembl:ENSG00000150782 MIM:600953
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: IGIF; IL-18; IL-1g; IL1F4
Summary: The protein encoded by this gene is a proinflammatory cytokine of the IL-1 family that is constitutively found as a precursor within the cytoplasm of a variety of cells including macrophages and keratinocytes. The inactive IL-18 precursor is processed to its active form by caspase-1, and is capable of stimulating interferon gamma production, and of regulating both T helper (Th) 1 and Th2 responses. This cytokine has been implicated in the injury of different organs, and in potentially fatal conditions characterized by a cytokine storm. In humans, IL-18 gene is located on chromosome 11. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in cytokine storm inflammatory response.
Expression: Biased expression in skin (RPKM 65.5), esophagus (RPKM 50.9) and 12 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q23.1

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	11	NC_000011.10 (112143251..112164104, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (112013983..112034817, complement)

Chromosome 11 - NC_000011.10 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?

IL18 signaling promotes homing of mature Tregs into the thymus.
Title: IL18 signaling promotes homing of mature Tregs into the thymus.
Cellular Models and Assays to Study NLRP3 Inflammasome Biology.
Title: Cellular Models and Assays to Study NLRP3 Inflammasome Biology.
IL-18/IL-18R1 promotes circulating fibrocyte differentiation in the aging population.
Title: IL-18/IL-18R1 promotes circulating fibrocyte differentiation in the aging population.
Ebola virus glycoprotein stimulates IL-18-dependent natural killer cell responses.
Title: Ebola virus glycoprotein stimulates IL-18-dependent natural killer cell responses.
Elevated IL18 levels in Nasopharyngeal carcinoma induced PD-1 expression on NK cells in TILS leading to poor prognosis.
Title: Elevated IL18 levels in Nasopharyngeal carcinoma induced PD-1 expression on NK cells in TILS leading to poor prognosis.
IL-18: a suggested target for immunomodulation in chikungunya virus infection.
Title: IL-18: a suggested target for immunomodulation in chikungunya virus infection.
Associations of genetic polymorphisms in CTLA-4 and IL-18 with chronic liver diseases: Evidence from a meta-analysis.
Title: Associations of genetic polymorphisms in CTLA-4 and IL-18 with chronic liver diseases: Evidence from a meta-analysis.
Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19.
Title: Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19.
Interleukin-18 promoter -137 G/C polymorphism (rs187238) is associated with biochemical markers of renal function and cardiovascular disease in type 2 diabetes patients.
Title: Interleukin-18 promoter -137 G/C polymorphism (rs187238) is associated with biochemical markers of renal function and cardiovascular disease in type 2 diabetes patients.
Effect of interleukins (IL-2, IL-15, IL-18) on receptors activation and cytotoxic activity of natural killer cells in breast cancer cell.
Title: Effect of interleukins (IL-2, IL-15, IL-18) on receptors activation and cytotoxic activity of natural killer cells in breast cancer cell.

Submit: New GeneRIF Correction See all GeneRIFs (897)

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

Associated conditions

Description	Tests
A genome-wide association study identifies protein quantitative trait loci (pQTLs). GeneReviews: Not available
Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels. GeneReviews: Not available
Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults. GeneReviews: Not available

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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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	Both acute HIV-1 infection and incubation of the THP-1 monocytes with HIV-1 Nef downregulate IL-18 expression	PubMed
Tat	tat	HIV-1 Tat upregulates the expression of interleukin 18 gene (IL18) in mammary epithelial cells	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

RH38662 (e-PCR)
- UniSTS:88341

RH80030 (e-PCR)
- UniSTS:87680

IL18_1978 (e-PCR)
- UniSTS:280780

Homology

Homologs of the IL18 gene: The IL18 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Orthologs from Annotation Pipeline: 245 organisms have orthologs with human gene IL18
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cytokine activity	IDA Inferred from Direct Assay more info	PubMed
cytokine activity	ISS Inferred from Sequence or Structural Similarity more info
cytokine activity	TAS Traceable Author Statement more info	PubMed
interleukin-18 receptor binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
T-helper 1 type immune response	IDA Inferred from Direct Assay more info	PubMed
activation of protein kinase B activity	IDA Inferred from Direct Assay more info	PubMed
angiogenesis	IDA Inferred from Direct Assay more info	PubMed
cell population proliferation	IEA Inferred from Electronic Annotation more info
cell-cell signaling	TAS Traceable Author Statement more info	PubMed
cellular response to organic cyclic compound	IDA Inferred from Direct Assay more info	PubMed
chemokine production	TAS Traceable Author Statement more info	PubMed
cholesterol homeostasis	ISS Inferred from Sequence or Structural Similarity more info
cytokine-mediated signaling pathway	TAS Traceable Author Statement more info
inflammatory response	IDA Inferred from Direct Assay more info	PubMed
interferon-gamma production	TAS Traceable Author Statement more info	PubMed
interleukin-13 production	TAS Traceable Author Statement more info	PubMed
interleukin-18-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
interleukin-18-mediated signaling pathway	TAS Traceable Author Statement more info
lipopolysaccharide-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
natural killer cell activation	IEA Inferred from Electronic Annotation more info
natural killer cell mediated cytotoxicity	IEA Inferred from Electronic Annotation more info
negative regulation of myoblast differentiation	IEA Inferred from Electronic Annotation more info
neutrophil activation	IEA Inferred from Electronic Annotation more info
positive regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of NIK/NF-kappaB signaling	IEA Inferred from Electronic Annotation more info
positive regulation of NK T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of T-helper 1 cell cytokine production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of T-helper 2 cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of activated T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
positive regulation of granulocyte macrophage colony-stimulating factor production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of inflammatory response	IC Inferred by Curator more info	PubMed
positive regulation of interferon-gamma production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of interleukin-17 production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of macrophage derived foam cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of natural killer cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of neuroinflammatory response	TAS Traceable Author Statement more info	PubMed
positive regulation of phosphatidylinositol 3-kinase signaling	IDA Inferred from Direct Assay more info	PubMed
positive regulation of protein kinase B signaling	IDA Inferred from Direct Assay more info	PubMed
positive regulation of smooth muscle cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of tissue remodeling	IC Inferred by Curator more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of tyrosine phosphorylation of STAT protein	IDA Inferred from Direct Assay more info	PubMed
regulation of cell adhesion	IDA Inferred from Direct Assay more info	PubMed
sleep	ISS Inferred from Sequence or Structural Similarity more info	PubMed
triglyceride homeostasis	ISS Inferred from Sequence or Structural Similarity more info
type 2 immune response	TAS Traceable Author Statement more info	PubMed

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

General protein information

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Preferred Names: interleukin-18

Names: IFN-gamma-inducing factor; IL-1 gamma; iboctadekin; interleukin 18 (interferon-gamma-inducing factor); interleukin-1 gamma

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_028143.1 RefSeqGene

Range

5024..25858

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001243211.2 → NP_001230140.1 interleukin-18 isoform 2

See identical proteins and their annotated locations for NP_001230140.1

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as Delta3pro-IL-18) lacks an in-frame coding exon compared to variant 1. The encoded isoform (2) is shorter and may be resistant to proteolytic activation, compared to isoform 1.

Source sequence(s)

AY266351, BC007461

Consensus CDS

CCDS58180.1

UniProtKB/Swiss-Prot

Q14116

UniProtKB/TrEMBL

A0A024R3E0

Related

ENSP00000434561.1, ENST00000524595.5

Conserved Domains (1) summary

pfam00340
Location:74 → 180

IL1; Interleukin-1 / 18
NM_001386420.1 → NP_001373349.1 interleukin-18 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (3) represents the longest transcript, and differs in the 5' UTR compared to variant 1. Both variants 1 and 3 encode the same protein.

Source sequence(s)

AP002007, AP002884

Related

ENSP00000434161.1, ENST00000528832.1
NM_001562.4 → NP_001553.1 interleukin-18 isoform 1 precursor

See identical proteins and their annotated locations for NP_001553.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript, both variants 1 and 3 encode the same protein.

Source sequence(s)

AY266351, BC007461, D49950

Consensus CDS

CCDS44731.1

UniProtKB/Swiss-Prot

Q14116

Related

ENSP00000280357.7, ENST00000280357.12

Conserved Domains (1) summary

pfam00340
Location:78 → 184

IL1; Interleukin-1 / 18