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    IL18 interleukin 18 [ Homo sapiens (human) ]

    Gene ID: 3606, updated on 11-Nov-2018

    Summary

    Official Symbol
    IL18provided by HGNC
    Official Full Name
    interleukin 18provided by HGNC
    Primary source
    HGNC:HGNC:5986
    See related
    Ensembl:ENSG00000150782 MIM:600953; Vega:OTTHUMG00000167006
    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 current GRCh38.p12 (GCF_000001405.38) 11 NC_000011.10 (112143251..112164117, 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 Jun 15 11:32:44 2016

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat'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 
    regulation of signaling receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    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
      5001..25867
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001243211.1NP_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, BU633686
      Consensus CDS
      CCDS58180.1
      UniProtKB/Swiss-Prot
      Q14116
      UniProtKB/TrEMBL
      A0A024R3E0
      Related
      ENSP00000434561.1, OTTHUMP00000234750, ENST00000524595.5, OTTHUMT00000392410
      Conserved Domains (1) summary
      pfam00340
      Location:74180
      IL1; Interleukin-1 / 18
    2. NM_001562.3NP_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, BU633686, D49950
      Consensus CDS
      CCDS44731.1
      UniProtKB/Swiss-Prot
      Q14116
      Related
      ENSP00000280357.7, OTTHUMP00000234749, ENST00000280357.11, OTTHUMT00000392409
      Conserved Domains (1) summary
      pfam00340
      Location:78184
      IL1; Interleukin-1 / 18

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p12 Primary Assembly

      Range
      112143251..112164117 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, OTTHUMP00000234751, ENST00000528832.1, OTTHUMT00000392412
      Conserved Domains (1) summary
      pfam00340
      Location:78184
      IL1; Interleukin-1 / 18
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