Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT83XMPQ)

DOT Name Interleukin-18 receptor 1 (IL18R1)
Synonyms IL-18R-1; IL-18R1; EC 3.2.2.6; CD218 antigen-like family member A; CDw218a; IL1 receptor-related protein; IL-1Rrp; IL1R-rp; Interleukin-18 receptor alpha; IL-18R-alpha; IL-18Ralpha; CD antigen CD218a
Gene Name IL18R1
Related Disease
T-B+ severe combined immunodeficiency due to gamma chain deficiency ( )
Acute lymphocytic leukaemia ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
Advanced cancer ( )
Ankylosing spondylitis ( )
Asthma ( )
Autoimmune disease ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Childhood acute lymphoblastic leukemia ( )
Coeliac disease ( )
Glioblastoma multiforme ( )
Glioma ( )
Head-neck squamous cell carcinoma ( )
Hepatitis B virus infection ( )
Inflammatory bowel disease ( )
Lung cancer ( )
Lung carcinoma ( )
Myeloproliferative neoplasm ( )
Nasal polyp ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
rubella ( )
Severe combined immunodeficiency ( )
Small-cell lung cancer ( )
Tuberculosis ( )
Ulcerative colitis ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Allergic rhinitis ( )
Influenza ( )
Atopic dermatitis ( )
Bipolar disorder ( )
Crohn disease ( )
Leprosy ( )
leukaemia ( )
Leukemia ( )
Multiple sclerosis ( )
Neoplasm of esophagus ( )
Pancreatic cancer ( )
Psoriasis ( )
Schizophrenia ( )
Sclerosing cholangitis ( )
Seasonal allergic rhinitis ( )
Type-1 diabetes ( )
UniProt ID
IL18R_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3WO3; 3WO4; 4R6U
EC Number
3.2.2.6
Pfam ID
PF01582
Sequence
MNCRELPLTLWVLISVSTAESCTSRPHITVVEGEPFYLKHCSCSLAHEIETTTKSWYKSS
GSQEHVELNPRSSSRIALHDCVLEFWPVELNDTGSYFFQMKNYTQKWKLNVIRRNKHSCF
TERQVTSKIVEVKKFFQITCENSYYQTLVNSTSLYKNCKKLLLENNKNPTIKKNAEFEDQ
GYYSCVHFLHHNGKLFNITKTFNITIVEDRSNIVPVLLGPKLNHVAVELGKNVRLNCSAL
LNEEDVIYWMFGEENGSDPNIHEEKEMRIMTPEGKWHASKVLRIENIGESNLNVLYNCTV
ASTGGTDTKSFILVRKADMADIPGHVFTRGMIIAVLILVAVVCLVTVCVIYRVDLVLFYR
HLTRRDETLTDGKTYDAFVSYLKECRPENGEEHTFAVEILPRVLEKHFGYKLCIFERDVV
PGGAVVDEIHSLIEKSRRLIIVLSKSYMSNEVRYELESGLHEALVERKIKIILIEFTPVT
DFTFLPQSLKLLKSHRVLKWKADKSLSYNSRFWKNLLYLMPAKTVKPGRDEPEVLPVLSE
S
Function
Within the IL18 receptor complex, responsible for the binding of the pro-inflammatory cytokine IL18, but not IL1A nor IL1B. Involved in IL18-mediated IFNG synthesis from T-helper 1 (Th1) cells. Contributes to IL18-induced cytokine production, either independently of SLC12A3, or as a complex with SLC12A3.
Tissue Specificity
Highly expressed in leukocytes, spleen, lung. Also expressed, but at lower levels, in liver, small intestine, colon, prostate, thymus, placenta, and heart. Specifically coexpressed with IL18R1 in Th1 cells .
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Viral protein interaction with cytokine and cytokine receptor (hsa04061 )
TNF sig.ling pathway (hsa04668 )
Inflammatory bowel disease (hsa05321 )
Reactome Pathway
Interleukin-18 signaling (R-HSA-9012546 )
Interleukin-37 signaling (R-HSA-9008059 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
T-B+ severe combined immunodeficiency due to gamma chain deficiency DISDB6K2 Definitive Genetic Variation [1]
Acute lymphocytic leukaemia DISPX75S Strong Genetic Variation [2]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [3]
Adult glioblastoma DISVP4LU Strong Altered Expression [4]
Advanced cancer DISAT1Z9 Strong Biomarker [5]
Ankylosing spondylitis DISRC6IR Strong Biomarker [6]
Asthma DISW9QNS Strong Genetic Variation [7]
Autoimmune disease DISORMTM Strong Biomarker [8]
Bladder cancer DISUHNM0 Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Altered Expression [10]
Breast carcinoma DIS2UE88 Strong Altered Expression [11]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Genetic Variation [2]
Coeliac disease DISIY60C Strong Biomarker [12]
Glioblastoma multiforme DISK8246 Strong Genetic Variation [13]
Glioma DIS5RPEH Strong Altered Expression [13]
Head-neck squamous cell carcinoma DISF7P24 Strong Altered Expression [14]
Hepatitis B virus infection DISLQ2XY Strong Genetic Variation [15]
Inflammatory bowel disease DISGN23E Strong Genetic Variation [16]
Lung cancer DISCM4YA Strong Biomarker [17]
Lung carcinoma DISTR26C Strong Biomarker [17]
Myeloproliferative neoplasm DIS5KAPA Strong Genetic Variation [18]
Nasal polyp DISLP3XE Strong Genetic Variation [19]
Neoplasm DISZKGEW Strong Biomarker [20]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [21]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [22]
rubella DISXUI9P Strong Biomarker [23]
Severe combined immunodeficiency DIS6MF4Q Strong Biomarker [24]
Small-cell lung cancer DISK3LZD Strong Biomarker [25]
Tuberculosis DIS2YIMD Strong Genetic Variation [26]
Ulcerative colitis DIS8K27O Strong Genetic Variation [27]
Urinary bladder cancer DISDV4T7 Strong Biomarker [9]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [9]
Allergic rhinitis DIS3U9HN moderate Genetic Variation [28]
Influenza DIS3PNU3 moderate Biomarker [29]
Atopic dermatitis DISTCP41 Limited Genetic Variation [30]
Bipolar disorder DISAM7J2 Limited Biomarker [31]
Crohn disease DIS2C5Q8 Limited Genetic Variation [16]
Leprosy DISAA4UI Limited Genetic Variation [32]
leukaemia DISS7D1V Limited Biomarker [33]
Leukemia DISNAKFL Limited Biomarker [33]
Multiple sclerosis DISB2WZI Limited Altered Expression [34]
Neoplasm of esophagus DISOLKAQ Limited Genetic Variation [35]
Pancreatic cancer DISJC981 Limited Biomarker [36]
Psoriasis DIS59VMN Limited Genetic Variation [27]
Schizophrenia DISSRV2N Limited Genetic Variation [37]
Sclerosing cholangitis DIS7GZNB Limited Genetic Variation [27]
Seasonal allergic rhinitis DIS58KQX Limited Genetic Variation [38]
Type-1 diabetes DIS7HLUB Limited Biomarker [39]
------------------------------------------------------------------------------------
⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Interleukin-18 receptor 1 (IL18R1). [40]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Interleukin-18 receptor 1 (IL18R1). [41]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Interleukin-18 receptor 1 (IL18R1). [42]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Interleukin-18 receptor 1 (IL18R1). [43]
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of Interleukin-18 receptor 1 (IL18R1). [44]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Interleukin-18 receptor 1 (IL18R1). [45]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Interleukin-18 receptor 1 (IL18R1). [46]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Interleukin-18 receptor 1 (IL18R1). [47]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of Interleukin-18 receptor 1 (IL18R1). [48]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Interleukin-18 receptor 1 (IL18R1). [49]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Interleukin-18 receptor 1 (IL18R1). [51]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of Interleukin-18 receptor 1 (IL18R1). [52]
------------------------------------------------------------------------------------
⏷ Show the Full List of 12 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Interleukin-18 receptor 1 (IL18R1). [50]
------------------------------------------------------------------------------------

References

1 Efficacy of gene therapy for X-linked severe combined immunodeficiency.N Engl J Med. 2010 Jul 22;363(4):355-64. doi: 10.1056/NEJMoa1000164.
2 Rapid Capture Next-Generation Sequencing in Clinical Diagnostics of Kinase Pathway Aberrations in B-Cell Precursor ALL.Pediatr Blood Cancer. 2016 Jul;63(7):1283-6. doi: 10.1002/pbc.25975. Epub 2016 Mar 23.
3 Cytokine receptor splice variants in hematologic diseases.Cytokine. 2020 Mar;127:154919. doi: 10.1016/j.cyto.2019.154919. Epub 2019 Dec 6.
4 Cytokine and cytokine receptor mRNA expression in human glioblastomas: evidence of Th1, Th2 and Th3 cytokine dysregulation.Acta Neuropathol. 2002 Feb;103(2):171-8. doi: 10.1007/s004010100448. Epub 2001 Nov 22.
5 Toll-like receptor 4 regulates spontaneous intestinal tumorigenesis by up-regulating IL-6 and GM-CSF.J Cell Mol Med. 2020 Jan;24(1):385-397. doi: 10.1111/jcmm.14742. Epub 2019 Oct 25.
6 Matrix Metalloproteinases and Synovial Joint Pathology.Prog Mol Biol Transl Sci. 2017;148:305-325. doi: 10.1016/bs.pmbts.2017.03.003. Epub 2017 May 4.
7 Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.Am J Hum Genet. 2019 Apr 4;104(4):665-684. doi: 10.1016/j.ajhg.2019.02.022. Epub 2019 Mar 28.
8 Alteration in gene expression profiles of thymoma: Genetic differences and potential novel targets.Thorac Cancer. 2019 May;10(5):1129-1135. doi: 10.1111/1759-7714.13053. Epub 2019 Apr 1.
9 Exploration of the pathways and interaction network involved in bladder cancer cell line with knockdown of Opa interacting protein 5.Pathol Res Pract. 2017 Sep;213(9):1059-1066. doi: 10.1016/j.prp.2017.07.029. Epub 2017 Aug 1.
10 Preclinical Activity of the Novel Anti-Prolactin Receptor (PRLR) Antibody-Drug Conjugate REGN2878-DM1 in PRLR-Positive Breast Cancers.Mol Cancer Ther. 2017 Jul;16(7):1299-1311. doi: 10.1158/1535-7163.MCT-16-0839. Epub 2017 Apr 4.
11 FLI1 expression is correlated with breast cancer cellular growth, migration, and invasion and altered gene expression.Neoplasia. 2014 Oct 23;16(10):801-13. doi: 10.1016/j.neo.2014.08.007. eCollection 2014 Oct.
12 Characterizing the genetic basis of innate immune response in TLR4-activated human monocytes.Nat Commun. 2014 Oct 20;5:5236. doi: 10.1038/ncomms6236.
13 Overexpression of oncostatin M receptor regulates local immune response in glioblastoma.J Cell Physiol. 2019 Sep;234(9):15496-15509. doi: 10.1002/jcp.28197. Epub 2019 Jan 28.
14 Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer.Hum Gene Ther Clin Dev. 2013 Sep;24(3):134-42. doi: 10.1089/humc.2013.144.
15 Comprehensive investigating of cytokine and receptor related genes variants in patients with chronic hepatitis B virus infection.Cytokine. 2018 Mar;103:10-14. doi: 10.1016/j.cyto.2017.12.017. Epub 2017 Dec 26.
16 Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.
17 Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation.Cancer Immunol Res. 2015 Aug;3(8):855-63. doi: 10.1158/2326-6066.CIR-15-0024. Epub 2015 May 26.
18 Myeloproliferative neoplasm stem cells.Blood. 2017 Mar 23;129(12):1607-1616. doi: 10.1182/blood-2016-10-696005. Epub 2017 Feb 3.
19 A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis.Nat Genet. 2019 Feb;51(2):267-276. doi: 10.1038/s41588-018-0314-6. Epub 2019 Jan 14.
20 CAR T cell therapy for breast cancer: harnessing the tumor milieu to drive T cell activation.J Immunother Cancer. 2018 May 10;6(1):34. doi: 10.1186/s40425-018-0347-5.
21 Co-expression changes of lncRNAs and mRNAs in the cervical sympathetic ganglia in diabetic cardiac autonomic neuropathic rats.J Neurosci Res. 2017 Aug;95(8):1690-1699. doi: 10.1002/jnr.24000. Epub 2016 Dec 19.
22 Identification of potential therapeutic target genes and mechanisms in non-small-cell lung carcinoma in non-smoking women based on bioinformatics analysis.Eur Rev Med Pharmacol Sci. 2015 Sep;19(18):3375-84.
23 Genetic polymorphisms associated with rubella virus-specific cellular immunity following MMR vaccination.Hum Genet. 2014 Nov;133(11):1407-17. doi: 10.1007/s00439-014-1471-z. Epub 2014 Aug 7.
24 Absence of -Chain in Keratinocytes Alters Chemokine Secretion, Resulting in Reduced Immune Cell Recruitment.J Invest Dermatol. 2017 Oct;137(10):2120-2130. doi: 10.1016/j.jid.2017.05.024. Epub 2017 Jun 17.
25 Chronic Obstructive Pulmonary Disease Molecular Subtyping and Pathway Deviation-Based Candidate Gene Identification.Cell J. 2018 Oct;20(3):326-332. doi: 10.22074/cellj.2018.5412. Epub 2018 May 15.
26 A proline deletion in IFNAR1 impairs IFN-signaling and underlies increased resistance to tuberculosis in humans.Nat Commun. 2018 Jan 8;9(1):85. doi: 10.1038/s41467-017-02611-z.
27 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
28 Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.Nat Genet. 2018 Aug;50(8):1072-1080. doi: 10.1038/s41588-018-0157-1. Epub 2018 Jul 16.
29 Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N-glycosylation.Int J Mol Med. 2018 Nov;42(5):2776-2792. doi: 10.3892/ijmm.2018.3863. Epub 2018 Sep 7.
30 Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.Nat Genet. 2015 Dec;47(12):1449-1456. doi: 10.1038/ng.3424. Epub 2015 Oct 19.
31 Transcriptome Changes in Relation to Manic Episode.Front Psychiatry. 2019 May 1;10:280. doi: 10.3389/fpsyt.2019.00280. eCollection 2019.
32 Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy.Nat Genet. 2015 Mar;47(3):267-71. doi: 10.1038/ng.3212. Epub 2015 Feb 2.
33 c-MPL provides tumor-targeted T-cell receptor-transgenic T cells with costimulation and cytokine signals.Blood. 2017 Dec 21;130(25):2739-2749. doi: 10.1182/blood-2017-02-769463. Epub 2017 Oct 27.
34 Multiple sclerosis treatment effects on plasma cytokine receptor levels.Clin Immunol. 2018 Feb;187:15-25. doi: 10.1016/j.clim.2017.08.023. Epub 2017 Sep 21.
35 Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.Nat Genet. 2012 Oct;44(10):1090-7. doi: 10.1038/ng.2411. Epub 2012 Sep 9.
36 Bioinformatics method to analyze the mechanism of pancreatic cancer disorder.J Comput Biol. 2013 Jun;20(6):444-52. doi: 10.1089/cmb.2012.0281. Epub 2013 Apr 24.
37 Potential involvement of the interleukin-18 pathway in schizophrenia.J Psychiatr Res. 2016 Mar;74:10-6. doi: 10.1016/j.jpsychires.2015.12.013. Epub 2015 Dec 15.
38 Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.J Allergy Clin Immunol. 2014 Jun;133(6):1564-71. doi: 10.1016/j.jaci.2013.10.030. Epub 2013 Dec 31.
39 Homing receptor expression is deviated on CD56+ blood lymphocytes during pregnancy in Type 1 diabetic women.PLoS One. 2015 Mar 20;10(3):e0119526. doi: 10.1371/journal.pone.0119526. eCollection 2015.
40 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
41 Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
42 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
43 Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
44 Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010 Jan 15;408(4):760-7. doi: 10.1016/j.scitotenv.2009.11.016. Epub 2009 Dec 4.
45 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
46 Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells. Br J Cancer. 2007 Oct 22;97(8):1099-105. doi: 10.1038/sj.bjc.6604003. Epub 2007 Sep 25.
47 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
48 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
49 Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression. Cell Rep. 2015 Sep 29;12(12):1986-96. doi: 10.1016/j.celrep.2015.08.046. Epub 2015 Sep 17.
50 Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
51 Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
52 The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.