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
109.20211119	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?

Association between TNF-alpha, Interleukin-18 Polymorphisms and Risk of Hepatocellular Carcinoma in Egyptian patients.
Title: Association between TNF-α, Interleukin-18 Polymorphisms and Risk of Hepatocellular Carcinoma in Egyptian patients.
Interleukin-18 promotes the antitumor ability of natural killer cells in colorectal cancer via the miR-574-3p/TGF-beta1 axis.
Title: Interleukin-18 promotes the antitumor ability of natural killer cells in colorectal cancer via the miR-574-3p/TGF-β1 axis.
IL-18 variant increases risk of enhanced HBV DNA replication in chronic hepatitis.
Title: IL-18 variant increases risk of enhanced HBV DNA replication in chronic hepatitis.
High serum free IL-18 is associated with decreased omalizumab efficacy: findings from a 2-year omalizumab treatment study.
Title: High serum free IL-18 is associated with decreased omalizumab efficacy: findings from a 2-year omalizumab treatment study.
Frequency of Interleukins IL1ss/IL18 and Inflammasome NLRP1/NLRP3 Polymorphisms in Sickle Cell Anemia Patients and their Association with Severity Score.
Title: Frequency of Interleukins IL1ß/IL18 and Inflammasome NLRP1/NLRP3 Polymorphisms in Sickle Cell Anemia Patients and their Association with Severity Score.
Elevated urinary IL-36alpha and IL-18 levels are associated with diabetic nephropathy in patients with type 2 diabetes mellitus.
Title: Elevated urinary IL-36α and IL-18 levels are associated with diabetic nephropathy in patients with type 2 diabetes mellitus.
Investigation of the roles of IL-18 (-607 C/A) and IL-18 (-137 G/C) gene variations in bladder cancer development: case-control study.
Title: Investigation of the roles of IL-18 (-607 C/A) and IL-18 (-137 G/C) gene variations in bladder cancer development: case-control study.
The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women.
Title: The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women.
Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells.
Title: Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells.
Elevated levels of IL-18 associated with schizophrenia and first episode psychosis: A systematic review and meta-analysis.
Title: Elevated levels of IL-18 associated with schizophrenia and first episode psychosis: A systematic review and meta-analysis.

Submit: New GeneRIF Correction See all GeneRIFs (938)

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

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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: 266 organisms have orthologs with human gene IL18
Orthologs

Gene Ontology Provided by GOA

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

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

Conserved Domains (1) summary

pfam00340
Location:73 → 185

IL1; Interleukin-1 / 18
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:73 → 185

IL1; Interleukin-1 / 18