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FLASH GENE

Symbol

IL18

contributors: mct/ - updated : 18-10-2017

HGNC name	interleukin 18 (interferon-gamma-inducing factor)
HGNC id	5986

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly   liver           stomach       highly Skin/Tegument skin         Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Lymphoid/Immune B cell Lymphoid/Immune macrophage

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a ligand binding domain with three Ig-like domains, including AA Glu42 and Lys8 crucial for structure and function
	a short cytoplasmic domain required for signaling

isoforms

Precursor

HOMOLOGY

interspecies

homolog to murine Igif (65 p 100)

Homologene

FAMILY	interleukin family
	IL-1 family

CATEGORY

secretory , signaling cytokine

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
text	transmembrane protein

basic FUNCTION	inducing interferon-gamma production of T cells
	involved in Th1-mediated cellular immunity
	important regulator of both innate and acquired immune responses
	can regulate osteoblast and osteoclast function
	plays an important role in chronic inflammation and autoimmune disorders

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

immunity/defense , inflammation

text	innate and acquired immunity, induction of apoptosis via DEATH domain receptors

PATHWAY

metabolism

signaling

signal transduction

	host response against pathogens, NF-kappa B signaling pathway
	inflammasome pathway, including NLRP6, PYCARD, CASP1, and IL18

a component

INTERACTION

DNA

RNA

small molecule

protein	IL18BP neutralizing IL18, competing with IL18R1
	interacting with NFKBIZ (NFKBIZ is critical for activation of NK cells in response to IL12B and IL18)
	TICAM2 serves as the sorting adaptor for MYD88 in IL18 signaling, which then facilitates the signal transduction
	IL22 induces IL18 expression from epithelial cells during intestinal infection

cell & other

interactions between IL18 and neutrophils (support a role for these cells in influencing both innate and adaptive immunity)

REGULATION

activated by

and cleaved by caspase 1

Other	negatively regulated by IL18BP
	regulated by neutrophils during early innate immune responses

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

to autoimmune (Crohn disease) to inflammatory, infectious diseases (intracellular bacteria) to insulin dependent diabetes mellitus to periodontitis, rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis to asthma to Behçet's disease, particularly to the mucocutaneous form to systemic lupus erythematosus (SLE) to tuberculosis (TB)

Variant & Polymorphism SNP , other	IDD, colonic mucosa (Crohn)
	polymorphism 105A/C significantly associated to asthma asthma
	promoter polymorphisms confer susceptibility to Behçet's disease, particularly to the mucocutaneous form
	rs360719 variant may play an important role in determining the susceptibility to SLE and it could be a key factor in the expression of the IL18 gene
	association between IL18 polymorphisms and TB

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology     antibody specific for cytokine, IL18-binding protein as therapeutic targets in rheumatoid arthritis immunology autoimmune multiple sclerosis therapeutic inhibition of IL18 might decrease demyelination but enhance remyelination, which has broad implications for demyelinating diseases

ANIMAL & CELL MODELS