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IL18 interleukin 18 [ Homo sapiens (human) ]

Gene ID: 3606, updated on 8-Oct-2019

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 that augments natural killer cell activity in spleen cells, and stimulates interferon gamma production in T-helper type I cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2011]
Expression
Biased expression in skin (RPKM 65.5), esophagus (RPKM 50.9) and 12 other tissues See more
Orthologs

Genomic context

See IL18 in Genome Data Viewer
Location:
11q23.1
Exon count:
6
Annotation release Status Assembly Chr Location
109.20190905 current GRCh38.p13 (GCF_000001405.39) 11 NC_000011.10 (112143251..112164104, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (112013974..112034840, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene NKAP domain containing 1 Neighboring gene translocase of inner mitochondrial membrane 8 homolog B Neighboring gene succinate dehydrogenase complex subunit D Neighboring gene uncharacterized LOC107987164 Neighboring gene testis expressed 12

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

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

HIV-1 interactions

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

Pathways from BioSystems

  • African trypanosomiasis, organism-specific biosystem (from KEGG)
    African trypanosomiasis, organism-specific biosystemTrypanosoma brucei, the parasite responsible for African trypanosomiasis (sleeping sickness), are spread by the tsetse fly in sub-Saharan Africa. The parasites are able to pass through the blood-brai...
  • African trypanosomiasis, conserved biosystem (from KEGG)
    African trypanosomiasis, conserved biosystemTrypanosoma brucei, the parasite responsible for African trypanosomiasis (sleeping sickness), are spread by the tsetse fly in sub-Saharan Africa. The parasites are able to pass through the blood-brai...
  • Cellular roles of Anthrax toxin, organism-specific biosystem (from Pathway Interaction Database)
    Cellular roles of Anthrax toxin, organism-specific biosystem
    Cellular roles of Anthrax toxin
  • Corticotropin-releasing hormone signaling pathway, organism-specific biosystem (from WikiPathways)
    Corticotropin-releasing hormone signaling pathway, organism-specific biosystemCorticotropin-releasing hormone (CRH) is a neuropeptide secreted abundantly in the paraventricular nucleus of the hypothalamus, amygdala, cerebral cortex and cerebellum in the central nervous system ...
  • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
    Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
  • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Cytosolic DNA-sensing pathway, organism-specific biosystem (from KEGG)
    Cytosolic DNA-sensing pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified s...
  • Cytosolic DNA-sensing pathway, conserved biosystem (from KEGG)
    Cytosolic DNA-sensing pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified s...
  • Development and heterogeneity of the ILC family, organism-specific biosystem (from WikiPathways)
    Development and heterogeneity of the ILC family, organism-specific biosystemDevelopment and heterogeneity of the ILC family. ILCs develop from distinct progenitors in the fetal liver or bone marrow and then develop into mature ILCs in the periphery. Different transcription f...
  • Hypertrophy Model, organism-specific biosystem (from WikiPathways)
    Hypertrophy Model, organism-specific biosystem
    Hypertrophy Model
  • IL1 and megakaryocytes in obesity, organism-specific biosystem (from WikiPathways)
    IL1 and megakaryocytes in obesity, organism-specific biosystemSchematic of the effects of interleukin (IL)1-beta/IL1R1 on megakaryocyte and platelet function. A high fat diet will cause megakaryocytes to produce platelets with an increase in both inflammatory a...
  • IL12 signaling mediated by STAT4, organism-specific biosystem (from Pathway Interaction Database)
    IL12 signaling mediated by STAT4, organism-specific biosystem
    IL12 signaling mediated by STAT4
  • IL12-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    IL12-mediated signaling events, organism-specific biosystem
    IL12-mediated signaling events
  • IL23-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    IL23-mediated signaling events, organism-specific biosystem
    IL23-mediated signaling events
  • IL27-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    IL27-mediated signaling events, organism-specific biosystem
    IL27-mediated signaling events
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Inflammatory bowel disease (IBD), organism-specific biosystem (from KEGG)
    Inflammatory bowel disease (IBD), organism-specific biosystemInflammatory bowel disease (IBD), which includes Crohn disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract due to environmental and geneti...
  • Inflammatory bowel disease (IBD), conserved biosystem (from KEGG)
    Inflammatory bowel disease (IBD), conserved biosystemInflammatory bowel disease (IBD), which includes Crohn disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract due to environmental and geneti...
  • Influenza A, organism-specific biosystem (from KEGG)
    Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Influenza A, conserved biosystem (from KEGG)
    Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Interleukin-1 processing, organism-specific biosystem (from REACTOME)
    Interleukin-1 processing, organism-specific biosystemThe IL-1 family of cytokines that interact with the Type 1 IL-1R include IL-1 Alpha (IL1A), IL-1 Beta (IL1B) and the IL-1 receptor antagonist protein (IL1RAP). IL1RAP is synthesized with a signal pep...
  • Interleukin-10 signaling, organism-specific biosystem (from REACTOME)
    Interleukin-10 signaling, organism-specific biosystemInterleukin-10 (IL10) was originally described as a factor named cytokine synthesis inhibitory factor that inhibited T-helper (Th) 1 activation and Th1 cytokine production (Fiorentino et al. 1989). ...
  • Interleukin-4 and 13 signaling, organism-specific biosystem (from REACTOME)
    Interleukin-4 and 13 signaling, organism-specific biosystemInterleukin-4 (IL4) is a principal regulatory cytokine during the immune response, crucially important in allergy and asthma (Nelms et al. 1999). When resting T cells are antigen-activated and expand...
  • Legionellosis, organism-specific biosystem (from KEGG)
    Legionellosis, organism-specific biosystemLegionellosis is a potentially fatal infectious disease caused by the bacterium Legionella pneumophila and other legionella species. Two distinct clinical and epidemiological syndromes are associated...
  • Legionellosis, conserved biosystem (from KEGG)
    Legionellosis, conserved biosystemLegionellosis is a potentially fatal infectious disease caused by the bacterium Legionella pneumophila and other legionella species. Two distinct clinical and epidemiological syndromes are associated...
  • Malaria, organism-specific biosystem (from KEGG)
    Malaria, organism-specific biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
  • Malaria, conserved biosystem (from KEGG)
    Malaria, conserved biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
  • NOD-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    NOD-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
  • NOD-like receptor signaling pathway, conserved biosystem (from KEGG)
    NOD-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
  • Nucleotide-binding Oligomerization Domain (NOD) pathway, organism-specific biosystem (from WikiPathways)
    Nucleotide-binding Oligomerization Domain (NOD) pathway, organism-specific biosystemThe NOD (nucleotide-binding oligomerization domain) proteins NOD1 and NOD2 have important roles in innate immunity as sensors of microbial components derived from bacterial peptidoglycan. The importa...
  • Rheumatoid arthritis, organism-specific biosystem (from KEGG)
    Rheumatoid arthritis, organism-specific biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
  • Rheumatoid arthritis, conserved biosystem (from KEGG)
    Rheumatoid arthritis, conserved biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
  • Salmonella infection, organism-specific biosystem (from KEGG)
    Salmonella infection, organism-specific biosystemSalmonella infection usually presents as a self-limiting gastroenteritis or the more severe typhoid fever and bacteremia. The common disease-causing Salmonella species in human is a single species, S...
  • Salmonella infection, conserved biosystem (from KEGG)
    Salmonella infection, conserved biosystemSalmonella infection usually presents as a self-limiting gastroenteritis or the more severe typhoid fever and bacteremia. The common disease-causing Salmonella species in human is a single species, S...
  • Signaling by Interleukins, organism-specific biosystem (from REACTOME)
    Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...
  • Tuberculosis, organism-specific biosystem (from KEGG)
    Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Tuberculosis, conserved biosystem (from KEGG)
    Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC12320

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 cell cytokine production IEA
Inferred from Electronic Annotation
more info
 
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 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 biosynthetic process 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
 
granulocyte macrophage colony-stimulating factor biosynthetic process TAS
Traceable Author Statement
more info
PubMed 
inflammatory response IDA
Inferred from Direct Assay
more info
PubMed 
interferon-gamma biosynthetic process TAS
Traceable Author Statement
more info
PubMed 
interleukin-13 biosynthetic process 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
 
interleukin-2 biosynthetic process TAS
Traceable Author Statement
more info
PubMed 
interleukin-6 production IEA
Inferred from Electronic Annotation
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

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)

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

  1. NG_028143.1 RefSeqGene

    Range
    5024..25858
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001243211.2NP_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:74180
    IL1; Interleukin-1 / 18
  2. NM_001562.4NP_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 and longer transcript, and encodes the longer isoform (1).
    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:78184
    IL1; Interleukin-1 / 18

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20190905

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p13 Primary Assembly

    Range
    112143251..112164104 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011542805.1XP_011541107.1  interleukin-18 isoform X1

    See identical proteins and their annotated locations for XP_011541107.1

    UniProtKB/Swiss-Prot
    Q14116
    UniProtKB/TrEMBL
    A0A024R3E0
    Conserved Domains (1) summary
    pfam00340
    Location:74180
    IL1; Interleukin-1 / 18
  2. XM_011542806.2XP_011541108.1  interleukin-18 isoform X2

    See identical proteins and their annotated locations for XP_011541108.1

    UniProtKB/Swiss-Prot
    Q14116
    Related
    ENSP00000434161.1, ENST00000528832.1
    Conserved Domains (1) summary
    pfam00340
    Location:78184
    IL1; Interleukin-1 / 18
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