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)... See more...

Aliases for IL18 Gene

Aliases for IL18 Gene

  • Interleukin 18 2 3 5
  • IL-18 2 3 4
  • IL1F4 2 3 4
  • IGIF 2 3 4
  • Interleukin 18 (Interferon-Gamma-Inducing Factor) 2 3
  • IFN-Gamma-Inducing Factor 3 4
  • Interleukin-1 Gamma 3 4
  • Interleukin-18 3 4
  • Iboctadekin 3 4
  • IL-1 Gamma 3 4
  • IL-1g 2 3
  • Interferon-Gamma-Inducing Factor 2
  • Interferon Gamma-Inducing Factor 4
  • IL18 5

External Ids for IL18 Gene

Previous GeneCards Identifiers for IL18 Gene

  • GC11M114366
  • GC11M113526
  • GC11M112047
  • GC11M111551
  • GC11M111519
  • GC11M107938
  • GC11M112013

Summaries for IL18 Gene

Entrez Gene Summary for IL18 Gene

  • 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]

GeneCards Summary for IL18 Gene

IL18 (Interleukin 18) is a Protein Coding gene. Diseases associated with IL18 include Adult-Onset Still's Disease and Shigellosis. Among its related pathways are ERK Signaling and Toll-Like receptor Signaling Pathways. Gene Ontology (GO) annotations related to this gene include cytokine activity.

UniProtKB/Swiss-Prot Summary for IL18 Gene

  • A proinflammatory cytokine primarily involved in polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (Probable). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators (PubMed:14528293, PubMed:25500532). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (Probable) (PubMed:10653850).

Gene Wiki entry for IL18 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for IL18 Gene

Genomics for IL18 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for IL18 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around IL18 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for IL18

Top Transcription factor binding sites by QIAGEN in the IL18 gene promoter:
  • AP-1
  • ATF-2
  • NF-kappaB
  • NF-kappaB1
  • TBP

Genomic Locations for IL18 Gene

Latest Assembly
chr11:112,143,251-112,164,104
(GRCh38/hg38)
Size:
20,854 bases
Orientation:
Minus strand

Previous Assembly
chr11:112,013,983-112,034,817
(GRCh37/hg19 by Entrez Gene)
Size:
20,835 bases
Orientation:
Minus strand

chr11:112,013,974-112,034,840
(GRCh37/hg19 by Ensembl)
Size:
20,867 bases
Orientation:
Minus strand

Genomic View for IL18 Gene

Genes around IL18 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IL18 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IL18 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IL18 Gene

Proteins for IL18 Gene

  • Protein details for IL18 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14116-IL18_HUMAN
    Recommended name:
    Interleukin-18
    Protein Accession:
    Q14116
    Secondary Accessions:
    • O75599
    • Q6FGY3
    • Q6WWJ7

    Protein attributes for IL18 Gene

    Size:
    193 amino acids
    Molecular mass:
    22326 Da
    Quaternary structure:
    • Forms a ternary complex with ligand-binding receptor subunit IL18R1 and signaling receptor subunit IL18RAP at the plasma membrane. Mature IL18 first binds to IL18R1 forming a low affinity binary complex, which then interacts with IL18RAP to form a high affinity ternary complex that signals inside the cell (PubMed:25261253, PubMed:14528293, PubMed:25500532). Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (PubMed:32272059).
    Miscellaneous:
    • [Isoform 2]: Expressed in ovarian carcinoma but undetectable in normal ovarian epithelial cells. Resistant to proteolytic activation by caspase-1 and -4.

    Three dimensional structures from OCA and Proteopedia for IL18 Gene

    Alternative splice isoforms for IL18 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IL18 Gene

Post-translational modifications for IL18 Gene

  • The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield the active form.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for IL18 Gene

Antibodies for research

  • Abcam antibodies for IL18

No data available for DME Specific Peptides for IL18 Gene

Domains & Families for IL18 Gene

Gene Families for IL18 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Candidate cardiovascular disease genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for IL18 Gene

InterPro:
Blocks:
  • Interleukin-1 precursor family signature
ProtoNet:

Suggested Antigen Peptide Sequences for IL18 Gene

GenScript: Design optimal peptide antigens:
  • Interleukin-18 (B0YJ28_HUMAN)
  • Interleukin-1 gamma (IL18_HUMAN)
  • Interleukin-18 (Q9NQ49_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q14116

UniProtKB/Swiss-Prot:

IL18_HUMAN :
  • Belongs to the IL-1 family.
Family:
  • Belongs to the IL-1 family.
genes like me logo Genes that share domains with IL18: view

Function for IL18 Gene

Molecular function for IL18 Gene

UniProtKB/Swiss-Prot Function:
A proinflammatory cytokine primarily involved in polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (Probable). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators (PubMed:14528293, PubMed:25500532). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (Probable) (PubMed:10653850).
UniProtKB/Swiss-Prot Induction:
In macrophages, release is increased by endocannabinoid anandamide/AEA.
GENATLAS Biochemistry:
interleukin 18,interferon-gamma inducing factor,involved in Th1-mediated cellular immunity

Phenotypes From GWAS Catalog for IL18 Gene

Gene Ontology (GO) - Molecular Function for IL18 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity ISS,TAS 11598150
GO:0005515 protein binding IPI 19104048
GO:0045515 interleukin-18 receptor binding IDA 14528293
genes like me logo Genes that share ontologies with IL18: view
genes like me logo Genes that share phenotypes with IL18: view

Animal Models for IL18 Gene

MGI Knock Outs for IL18:
  • Il18 Il18<tm1Aki>
  • Il18 Il18<tm1Khe>
  • Il18 Il18<tm1Liew>
  • Il18 Il18<tm1b(EUCOMM)Wtsi>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IL18

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for IL18 Gene

Localization for IL18 Gene

Subcellular locations from UniProtKB/Swiss-Prot for IL18 Gene

Cytoplasm. Secreted. Note=The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion. {ECO:0000269 PubMed:32272059}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for IL18 gene
Compartment Confidence
extracellular 5
cytosol 5
nucleus 4
plasma membrane 3
cytoskeleton 3
mitochondrion 3
endosome 3
lysosome 3
golgi apparatus 3
peroxisome 2
endoplasmic reticulum 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Golgi apparatus (2)
  • Nucleoplasm (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for IL18 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS 11598150
GO:0005615 extracellular space IDA 21323571
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with IL18: view

Pathways & Interactions for IL18 Gene

PathCards logo

SuperPathways for IL18 Gene

SuperPathway Contained pathways
1 PEDF Induced Signaling
.94
.94
.73
.71
.62
.61
.57
.51
.47
.46
.43
2 TGF-Beta Pathway
.60
.60
.57
.43
.40
3 Toll-Like receptor Signaling Pathways
4 Akt Signaling
.60
.60
.55
5 ERK Signaling
.61
.61
.51
genes like me logo Genes that share pathways with IL18: view

Pathways by source for IL18 Gene

1 GeneGo (Thomson Reuters) pathway for IL18 Gene
  • Immune response IL-12-induced IFN-gamma production
27 Qiagen pathways for IL18 Gene
  • Akt Signaling
  • all-trans-Retinoic Acid Signaling in Brain
  • Antioxidant Action of Vitamin-C
  • Cytokine Network
  • Endothelin-1 Signaling Pathway

SIGNOR curated interactions for IL18 Gene

Activates:

Gene Ontology (GO) - Biological Process for IL18 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IMP 21147091
GO:0001525 angiogenesis IDA 11466388
GO:0006954 inflammatory response IDA 21147091
GO:0006955 immune response IEA --
GO:0007165 signal transduction IEA --
genes like me logo Genes that share ontologies with IL18: view

Drugs & Compounds for IL18 Gene

(85) Drugs for IL18 Gene - From: PharmGKB, DGIdb, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Ribavirin Approved Pharma 1081
Tacrolimus Approved, Investigational Pharma 1315
interferons Pharma 2216
IAP Antagonist Pharma antibody, modulator 0
Iboctadekin + Doxil Pharma inhibitor, modulator 0

(55) Additional Compounds for IL18 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with IL18: view

Transcripts for IL18 Gene

mRNA/cDNA for IL18 Gene

3 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IL18

Alternative Splicing Database (ASD) splice patterns (SP) for IL18 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7
SP1: - - - -
SP2: - -
SP3: -
SP4:
SP5:

Relevant External Links for IL18 Gene

GeneLoc Exon Structure for
IL18

Expression for IL18 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for IL18 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for IL18 Gene

This gene is overexpressed in Esophagus - Mucosa (x7.1), Skin - Sun Exposed (Lower leg) (x6.4), Skin - Not Sun Exposed (Suprapubic) (x6.0), and Vagina (x4.5).

Protein differential expression in normal tissues from HIPED for IL18 Gene

This gene is overexpressed in Lymph node (11.0), Oral epithelium (10.0), and Heart (8.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for IL18 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for IL18

SOURCE GeneReport for Unigene cluster for IL18 Gene:

Hs.83077

Evidence on tissue expression from TISSUES for IL18 Gene

  • Blood(4.7)
  • Liver(4.6)
  • Lymph node(3.6)
  • Spleen(3.6)
  • Skin(3.6)
  • Intestine(3.3)
  • Bone marrow(3.1)
  • Lung(3.1)
  • Kidney(3.1)
  • Heart(2.9)
  • Nervous system(2.9)
  • Muscle(2.7)
  • Stomach(2.6)
  • Pancreas(2.5)
  • Urine(2.4)
  • Adrenal gland(2.3)
  • Bone(2.2)
  • Gall bladder(2.2)
genes like me logo Genes that share expression patterns with IL18: view

Primer products for research

No data available for Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for IL18 Gene

Orthologs for IL18 Gene

This gene was present in the common ancestor of chordates.

Orthologs for IL18 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia IL18 30 31
  • 99.48 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia IL18 30 31
  • 86.36 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia IL18 30 31
  • 84.55 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Il18 30 17 31
  • 75.53 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Il18 30
  • 74.39 (n)
Oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 43 (a)
OneToMany
-- 31
  • 35 (a)
OneToMany
Platypus
(Ornithorhynchus anatinus)
Mammalia IL18 31
  • 36 (a)
OneToOne
Chicken
(Gallus gallus)
Aves IL18 31
  • 33 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia IL18 31
  • 29 (a)
OneToOne
Species where no ortholog for IL18 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for IL18 Gene

ENSEMBL:
Gene Tree for IL18 (if available)
TreeFam:
Gene Tree for IL18 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for IL18: view image

Paralogs for IL18 Gene

(1) SIMAP similar genes for IL18 Gene using alignment to 2 proteins:

  • IL18_HUMAN
  • B0YJ28_HUMAN
genes like me logo Genes that share paralogs with IL18: view

No data available for Paralogs for IL18 Gene

Variants for IL18 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for IL18 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs360722 Benign: Three Vessel Coronary Disease 112,155,980(-) A/G
NM_001562.4(IL18):c.-8-919T>C
INTRON
rs549908 Benign: Three Vessel Coronary Disease 112,150,193(-) T/G
NM_001562.4(IL18):c.105A>C (p.Ser35=)
SYNONYMOUS
rs5744251 Benign: not provided 112,153,608(-) G/T
NM_001562.4(IL18):c.80-5C>A
INTRON
rs5744280 Benign: Three Vessel Coronary Disease 112,145,791(-) G/A
NM_001562.4(IL18):c.361-1974C>T
INTRON
rs780550512 Likely Benign: not provided 112,150,082(-) A/C
NM_001562.4(IL18):c.216T>G (p.Ser72=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for IL18 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for IL18 Gene

Variant ID Type Subtype PubMed ID
esv2745077 CNV deletion 23290073
nsv1134175 CNV deletion 24896259
nsv519192 CNV gain 19592680

Variation tolerance for IL18 Gene

Residual Variation Intolerance Score: 68.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.06; 1.31% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for IL18 Gene

Human Gene Mutation Database (HGMD)
IL18
SNPedia medical, phenotypic, and genealogical associations of SNPs for
IL18

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for IL18 Gene

Disorders for IL18 Gene

MalaCards: The human disease database

(161) MalaCards diseases for IL18 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
adult-onset still's disease
  • adult onset still's disease
shigellosis
  • bacillary dysentery
pleural tuberculosis
  • pearly disease
noma
  • cancrum oris
smallpox
  • ordinary smallpox
- elite association - COSMIC cancer census association via MalaCards
Search IL18 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for IL18

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with IL18: view

No data available for UniProtKB/Swiss-Prot and Genatlas for IL18 Gene

Publications for IL18 Gene

  1. Association of single nucleotide polymorphisms in the IL-12 (IL-12A and B) and IL-12 receptor (IL-12Rbeta1 and beta2) genes and gene-gene interactions with atopic dermatitis in Koreans. (PMID: 20060272) Namkung JH … Yang JM (Journal of dermatological science 2010) 3 23 41
  2. [Correlations between serum interleukin-18 (IL-18) level, IL-18 gene promoter polymorphisms and the development of sepsis in children]. (PMID: 20441695) Cai LL … Zeng X (Zhonghua er ke za zhi = Chinese journal of pediatrics 2010) 3 23 41
  3. Genetic predisposition to natural rubber latex allergy differs between health care workers and high-risk patients. (PMID: 20418295) Monitto CL … Brown RH (Anesthesia and analgesia 2010) 3 23 41
  4. Lack of association between polymorphisms of the IL18R1 and IL18RAP genes and cardiovascular risk: the MORGAM Project. (PMID: 19473509) Grisoni ML … Tregouet DA (BMC medical genetics 2009) 3 23 41
  5. Analysis of inflammation- and atherosclerosis-related gene polymorphisms in branch retinal vein occlusion. (PMID: 19347053) Steinbrugger I … Weger M (Molecular vision 2009) 3 23 41

Products for IL18 Gene

Sources for IL18 Gene