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; AllianceGenome:HGNC:5986
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
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (112143260..112164094, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (112153592..112174423, complement)
RS_2024_09	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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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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?

Role of interleukin-18 in mediating the impacts of celiac disease on osteoporosis: a Mendelian randomization study.
Title: Role of interleukin-18 in mediating the impacts of celiac disease on osteoporosis: a Mendelian randomization study.
IL18 rs360717 and rs187238 genetic variants are associated with migraine diagnosis.
Title: IL18 rs360717 and rs187238 genetic variants are associated with migraine diagnosis.
Galectin-3, Galectin-9, and Interleukin-18 Are Associated with Monocyte/Macrophage Activation and Turnover More so than Simian Immunodeficiency Virus-Associated Cardiac Pathology or Encephalitis.
Title: Galectin-3, Galectin-9, and Interleukin-18 Are Associated with Monocyte/Macrophage Activation and Turnover More so than Simian Immunodeficiency Virus-Associated Cardiac Pathology or Encephalitis.
PTBP3 Mediates IL-18 Exon Skipping to Promote Immune Escape in Gallbladder Cancer.
Title: PTBP3 Mediates IL-18 Exon Skipping to Promote Immune Escape in Gallbladder Cancer.
Deciphering interleukin-18 in diabetes and its complications: Biological features, mechanisms, and therapeutic perspectives.
Title: Deciphering interleukin-18 in diabetes and its complications: Biological features, mechanisms, and therapeutic perspectives.
ACSL6-activated IL-18R1-NF-kappaB promotes IL-18-mediated tumor immune evasion and tumor progression.
Title: ACSL6-activated IL-18R1-NF-κB promotes IL-18-mediated tumor immune evasion and tumor progression.
Association of IL-18 gene polymorphisms with clinical aspects of hyperlipidemia in middle-aged and early people in the community.
Title: Association of IL-18 gene polymorphisms with clinical aspects of hyperlipidemia in middle-aged and early people in the community.
Relationships between Interleukin 18 -607 C/A and -137 G/C, Osteopontin -9250 C/T Genetic Polymorphisms and Systemic Inflammatory Response Syndrome in Coronary Artery Bypass Graft Surgery.
Title: Relationships between Interleukin 18 -607 C/A and -137 G/C, Osteopontin -9250 C/T Genetic Polymorphisms and Systemic Inflammatory Response Syndrome in Coronary Artery Bypass Graft Surgery.
Evaluating Single-Nucleotide Polymorphisms in Inflammasome Proteins and Serum Levels of IL-18 and IL-1beta in Kidney Interstitial Damage in Anti-Neutrophilic Cytoplasmic Antibody-Associated Vasculitis.
Title: Evaluating Single-Nucleotide Polymorphisms in Inflammasome Proteins and Serum Levels of IL-18 and IL-1β in Kidney Interstitial Damage in Anti-Neutrophilic Cytoplasmic Antibody-Associated Vasculitis.
Association of carotid atheroma plaque with IL-18 levels and with polymorphisms in the IL-18 receptor gene in a Mediterranean population.
Title: Association of carotid atheroma plaque with IL-18 levels and with polymorphisms in the IL-18 receptor gene in a Mediterranean population.

Submit: New GeneRIF Correction See all GeneRIFs (1047)

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
A genome-wide association study identifies protein quantitative trait loci (pQTLs). EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults. 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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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

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 T-helper 1 type immune response	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 cholesterol homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in defense response to Gram-positive bacterium	ISS Inferred from Sequence or Structural Similarity more info
involved_in establishment of skin barrier	ISS Inferred from Sequence or Structural Similarity more info
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in interleukin-18-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 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 inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
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 non-canonical NF-kappaB signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	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 type II interferon production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of type II interferon production	TAS Traceable Author Statement 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
is_active_in extracellular space	IDA Inferred from Direct Assay 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

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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/TrEMBL

B0YJ28

Related

ENSP00000434561.1, ENST00000524595.6

Conserved Domains (1) summary

pfam00340
Location:74 → 180

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

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

Consensus CDS

CCDS44731.1

UniProtKB/Swiss-Prot

O75599, Q14116, Q6FGY3, Q6WWJ7

UniProtKB/TrEMBL

Q96KJ8

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

O75599, Q14116, Q6FGY3, Q6WWJ7

UniProtKB/TrEMBL

Q96KJ8

Related

ENSP00000280357.7, ENST00000280357.12

Conserved Domains (1) summary

pfam00340
Location:73 → 185

IL1; Interleukin-1 / 18