IL18 (interleukin 18)

Gene

• Entrez ID: 3606
• Gene name: Interleukin 18
• Gene symbol: IL18
• Synonyms: IGIF, IL-18, IL-1g, IL1F4
• Chromosome: 11
• Chromosome location: 11q23.1
• 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

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004304	hsa-miR-346	qRT-PCR, Luciferase reporter assay, Western blot, Northern blot	19342689
MIRT054556	hsa-miR-197-3p	Microarray, qRT-PCR	23710316
MIRT438748	hsa-miR-130a-3p	ELISA, Luciferase reporter assay, qRT-PCR	24801815
MIRT438748	hsa-miR-130a-3p	ELISA, Luciferase reporter assay, qRT-PCR	24801815
MIRT1064132	hsa-miR-129-5p	CLIP-seq
MIRT1064133	hsa-miR-4252	CLIP-seq
MIRT1064134	hsa-miR-4304	CLIP-seq
MIRT1064135	hsa-miR-4438	CLIP-seq
MIRT1064136	hsa-miR-5095	CLIP-seq
MIRT2015262	hsa-miR-1307	CLIP-seq
MIRT2015263	hsa-miR-197	CLIP-seq
MIRT2015264	hsa-miR-4284	CLIP-seq
MIRT2015265	hsa-miR-4638-5p	CLIP-seq
MIRT2015262	hsa-miR-1307	CLIP-seq
MIRT2247554	hsa-miR-143	CLIP-seq
MIRT2015263	hsa-miR-197	CLIP-seq
MIRT2247555	hsa-miR-3149	CLIP-seq
MIRT2247556	hsa-miR-3155	CLIP-seq
MIRT2247557	hsa-miR-3155b	CLIP-seq
MIRT2247558	hsa-miR-3663-5p	CLIP-seq
MIRT2247559	hsa-miR-411	CLIP-seq
MIRT2015264	hsa-miR-4284	CLIP-seq
MIRT2247560	hsa-miR-4635	CLIP-seq
MIRT2015265	hsa-miR-4638-5p	CLIP-seq
MIRT2247561	hsa-miR-4716-5p	CLIP-seq
MIRT2247562	hsa-miR-4770	CLIP-seq
MIRT2247563	hsa-miR-4781-3p	CLIP-seq
MIRT2247564	hsa-miR-484	CLIP-seq
MIRT2247565	hsa-miR-5096	CLIP-seq
MIRT2015262	hsa-miR-1307	CLIP-seq
MIRT2015263	hsa-miR-197	CLIP-seq
MIRT2015264	hsa-miR-4284	CLIP-seq
MIRT2015265	hsa-miR-4638-5p	CLIP-seq
MIRT2015262	hsa-miR-1307	CLIP-seq
MIRT2015263	hsa-miR-197	CLIP-seq
MIRT2015264	hsa-miR-4284	CLIP-seq
MIRT2015265	hsa-miR-4638-5p	CLIP-seq
MIRT2015262	hsa-miR-1307	CLIP-seq
MIRT2015263	hsa-miR-197	CLIP-seq
MIRT2015264	hsa-miR-4284	CLIP-seq
MIRT2015265	hsa-miR-4638-5p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
HDAC9	Unknown	11944905
NFKB1	Activation	15963597;17399992
NFKB1	Unknown	10227974
RELA	Activation	15963597;17399992
RELA	Unknown	10227974
SPI1	Unknown	14991611

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	IMP	21147091
GO:0001525	Process	Angiogenesis	IDA	11466388
GO:0005125	Function	Cytokine activity	IDA	14528293, 25500532
GO:0005125	Function	Cytokine activity	ISS
GO:0005125	Function	Cytokine activity	TAS	11598150
GO:0005515	Function	Protein binding	IPI	19104048, 25261253, 32296183
GO:0005576	Component	Extracellular region	TAS	11598150
GO:0005615	Component	Extracellular space	IDA	21323571
GO:0005829	Component	Cytosol	TAS
GO:0006954	Process	Inflammatory response	IDA	21147091
GO:0007267	Process	Cell-cell signaling	TAS	9792649
GO:0008283	Process	Cell population proliferation	IEA
GO:0010744	Process	Positive regulation of macrophage derived foam cell differentiation	ISS
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	IDA	21321938
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0030101	Process	Natural killer cell activation	IEA
GO:0030155	Process	Regulation of cell adhesion	IDA	11477102
GO:0030431	Process	Sleep	ISS	11506998
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IDA	21147091
GO:0032148	Process	Activation of protein kinase B activity	IDA	21321938
GO:0032602	Process	Chemokine production	TAS	11598150
GO:0032609	Process	Interferon-gamma production	TAS	10227975
GO:0032616	Process	Interleukin-13 production	TAS	10227975
GO:0032725	Process	Positive regulation of granulocyte macrophage colony-stimulating factor production	IDA	20027291
GO:0032729	Process	Positive regulation of interferon-gamma production	IDA	10653850, 14528293, 19088061, 20027291
GO:0032740	Process	Positive regulation of interleukin-17 production	IDA	16482511
GO:0032819	Process	Positive regulation of natural killer cell proliferation	IDA	19088061
GO:0034105	Process	Positive regulation of tissue remodeling	IC	16482511
GO:0035655	Process	Interleukin-18-mediated signaling pathway	IDA	21321938, 25500532
GO:0035655	Process	Interleukin-18-mediated signaling pathway	TAS
GO:0042088	Process	T-helper 1 type immune response	IDA	8766574
GO:0042092	Process	Type 2 immune response	TAS	11905033
GO:0042104	Process	Positive regulation of activated T cell proliferation	IDA	8766574
GO:0042119	Process	Neutrophil activation	IEA
GO:0042267	Process	Natural killer cell mediated cytotoxicity	IEA
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	IDA	10903731
GO:0042632	Process	Cholesterol homeostasis	ISS
GO:0045515	Function	Interleukin-18 receptor binding	IDA	14528293, 25500532
GO:0045630	Process	Positive regulation of T-helper 2 cell differentiation	ISS
GO:0045662	Process	Negative regulation of myoblast differentiation	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	24615654
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IDA	21321938
GO:0050729	Process	Positive regulation of inflammatory response	IC	16482511
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IDA	25500532
GO:0051142	Process	Positive regulation of NK T cell proliferation	IDA	19088061
GO:0051897	Process	Positive regulation of protein kinase B signaling	IDA	21321938
GO:0070328	Process	Triglyceride homeostasis	ISS
GO:0071407	Process	Cellular response to organic cyclic compound	IDA	21147091
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	ISS	26656097
GO:0150078	Process	Positive regulation of neuroinflammatory response	TAS	26753638
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	IEA
GO:2000556	Process	Positive regulation of T-helper 1 cell cytokine production	IDA	10653850

Other IDs

• MIM: 600953
• HGNC: 5986
• e!Ensembl: ENSG00000150782

Protein

• UniProt ID: Q14116
• Protein name: Interleukin-18 (IL-18) (Iboctadekin) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
• Protein function: Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex whi
• PDB: 1J0S, 2VXT, 3F62, 3WO2, 3WO3, 3WO4, 4EEE, 4EKX, 4HJJ, 4R6U, 4XFS, 4XFT, 4XFU, 7AL7, 8J6K, 8SPB, 8SV1, 8URV
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00340	IL1	72 → 185	Interleukin-1 / 18	Domain

• Sequence:

  MAAEPVEDNCINFVAMKFIDNTLYFIAEDDENLESDYFGKLESKLSVIRNLNDQVLFIDQ
  GNRPLFEDMTDSDCRDNAPRTIFIISMYKDSQPRGMAVTISVKCEKISTLSCENKIISFK
  EMNPPDNIKDTKSDIIFFQRSVPGHDNKMQFESSSYEGYFLACEKERDLFKLILKKEDEL
  GDRSIMFTVQNED

• Sequence length: 193

Pathways

KEGG:

Cytokine-cytokine receptor interaction
Viral protein interaction with cytokine and cytokine receptor
NOD-like receptor signaling pathway
Cytosolic DNA-sensing pathway
Pathogenic Escherichia coli infection
Shigellosis
Salmonella infection
Legionellosis
Yersinia infection
African trypanosomiasis
Malaria
Tuberculosis
Influenza A
Inflammatory bowel disease
Rheumatoid arthritis
Lipid and atherosclerosis

Reactome:

Interleukin-1 processing
Interleukin-10 signaling
Interleukin-4 and Interleukin-13 signaling
Interleukin-18 signaling
Purinergic signaling in leishmaniasis infection

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Dermatitis	Contact Dermatitis, Dermatitis, Allergic Contact	rs61816761, rs150597413, rs138726443, rs201356558, rs149484917, rs372754256, rs747301529, rs567795279, rs745915174	25724174, 27585668
Glomerulonephritis	Glomerulonephritis	rs778043831	18462998
Metabolic syndrome	Metabolic Syndrome X	rs367643250, rs587777380, rs777736953	16644639
Prostate cancer	Malignant neoplasm of prostate	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	17688413
Rheumatoid arthritis	Rheumatoid Arthritis	rs3766379, rs3792876, rs2071592, rs3087456, rs587776843, rs1566328963, rs2240340, rs1557787212	16368150
Sarcoidosis	Sarcoidosis	rs2076530	16100009
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	18092318, 21510800
Tumoral calcinosis	Tumoral calcinosis	rs104894343, rs104894344, rs745655924, rs137853086, rs375879489, rs761396172, rs137853087, rs137853091, rs137853088, rs137853089, rs137853090, rs766750282, rs760830864, rs786205250, rs267606841, rs1555096583, rs1220533001, rs762936774, rs775341386	21335463

Unknown
Disease name	Disease term	dbSNP ID	References
Benign neoplasm	Benign Neoplasm		21273262
Bright disease	Bright Disease		18462998
Cardiac valvular disease	Heart valve disease		21335463
Cerebral ischemia	Brain Ischemia		15829914
Autoimmune hepatitis	Autoimmune Chronic Hepatitis		21227906
Malignant neoplasm	Malignant Neoplasms		21273262
Mental depression	Mental Depression, Depressive disorder	rs587778876, rs587778877	21962565, 16289586, 11226333, 11226333, 16289586, 21962565
Mouth neoplasms	Mouth Neoplasms		24349532
Malignant neoplasm of mouth	Malignant neoplasm of mouth		24349532
Neoplasms	Neoplasms		21273262
Prostatic neoplasms	Prostatic Neoplasms		17688413
Urticaria	Urticaria		18204966