Details of Drug Off-Target (DOT)

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

• DOT Name: Interleukin-20 receptor subunit alpha (IL20RA)
• Synonyms: IL-20 receptor subunit alpha; IL-20R-alpha; IL-20RA; Cytokine receptor class-II member 8; Cytokine receptor family 2 member 8; CRF2-8; IL-20R1; ZcytoR7
• Gene Name: IL20RA
• Related Disease:
  Neoplasm
  Asthma
  Crohn disease
  Non-small-cell lung cancer
  Pneumonia
  Pneumonitis
  Psoriasis
  Vitiligo
  Autoimmune disease
  Melanoma
  Type-1/2 diabetes
  Breast cancer
  Breast carcinoma
  Metastatic malignant neoplasm
  Non-alcoholic steatohepatitis
  Osteoarthritis
  Rheumatoid arthritis
• UniProt ID: I20RA_HUMAN
• PDB ID: 4DOH
• Pfam ID: PF09294 ; PF01108
• Sequence:
  MRAPGRPALRPLPLPPLLLLLLAAPWGRAVPCVSGGLPKPANITFLSINMKNVLQWTPPE
  GLQGVKVTYTVQYFIYGQKKWLNKSECRNINRTYCDLSAETSDYEHQYYAKVKAIWGTKC
  SKWAESGRFYPFLETQIGPPEVALTTDEKSISVVLTAPEKWKRNPEDLPVSMQQIYSNLK
  YNVSVLNTKSNRTWSQCVTNHTLVLTWLEPNTLYCVHVESFVPGPPRRAQPSEKQCARTL
  KDQSSEFKAKIIFWYVLPVSITVFLFSVMGYSIYRYIHVGKEKHPANLILIYGNEFDKRF
  FVPAEKIVINFITLNISDDSKISHQDMSLLGKSSDVSSLNDPQPSGNLRPPQEEEEVKHL
  GYASHLMEIFCDSEENTEGTSLTQQESLSRTIPPDKTVIEYEYDVRTTDICAGPEEQELS
  LQEEVSTQGTLLESQAALAVLGPQTLQYSYTPQLQDLDPLAQEHTDSEEGPEEEPSTTLV
  DWDPQTGRLCIPSLSSFDQDSEGCEPSEGDGLGEEGLLSRLYEEPAPDRPPGENETYLMQ
  FMEEWGLYVQMEN
• Function: The IL20RA/IL20RB dimer is a receptor for IL19, IL20 and IL24. The IL20RA/IL10RB dimer is a receptor for IL26.
• Tissue Specificity: Widely expressed with highest levels in skin and testis and high levels in brain. Highly expressed in psoriatic skin.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway: Interleukin-20 family signaling (R-HSA-8854691)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Asthma	DISW9QNS	Strong	Biomarker	[2]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Pneumonia	DIS8EF3M	Strong	Biomarker	[2]
Pneumonitis	DIS88E0K	Strong	Biomarker	[2]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[5]
Vitiligo	DISR05SL	Strong	Genetic Variation	[6]
Autoimmune disease	DISORMTM	moderate	Genetic Variation	[7]
Melanoma	DIS1RRCY	moderate	Altered Expression	[8]
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[9]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[10]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[10]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[10]
Non-alcoholic steatohepatitis	DIST4788	Limited	Biomarker	[11]
Osteoarthritis	DIS05URM	Limited	Altered Expression	[12]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[12]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interleukin-20 receptor subunit alpha (IL20RA).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interleukin-20 receptor subunit alpha (IL20RA).	[14]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Interleukin-20 receptor subunit alpha (IL20RA).	[16]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Interleukin-20 receptor subunit alpha (IL20RA).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Interleukin-20 receptor subunit alpha (IL20RA).	[19]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Interleukin-20 receptor subunit alpha (IL20RA).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Interleukin-20 receptor subunit alpha (IL20RA).	[18]

References

• [1] Promoter methylation of genes in and around the candidate lung cancer susceptibility locus 6q23-25.Cancer Res. 2008 Mar 15;68(6):1707-14. doi: 10.1158/0008-5472.CAN-07-6325.
• [2] Blocking IL-19 Signaling Ameliorates Allergen-Induced Airway Inflammation.Front Immunol. 2019 Apr 30;10:968. doi: 10.3389/fimmu.2019.00968. eCollection 2019.
• [3] mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn's Disease.Cells. 2019 Aug 18;8(8):924. doi: 10.3390/cells8080924.
• [4] IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF.Eur J Cancer. 2011 Aug;47(12):1908-18. doi: 10.1016/j.ejca.2011.04.012. Epub 2011 May 10.
• [5] Association analysis of IL20RA and IL20RB genes in psoriasis.Genes Immun. 2008 Jul;9(5):445-51. doi: 10.1038/gene.2008.36. Epub 2008 May 15.
• [6] Association analysis of genes of the IL19 cluster and their receptors in vitiligo patients.Dermatology. 2010;221(3):261-6. doi: 10.1159/000317526.
• [7] CRISPR/cas9 mediated knockout of an intergenic variant rs6927172 identified IL-20RA as a new risk gene for multiple autoimmune diseases.Genes Immun. 2019 Feb;20(2):103-111. doi: 10.1038/s41435-018-0011-6. Epub 2018 Feb 23.
• [8] Combination of adenoviruses expressing melanoma differentiation-associated gene-7 and chemotherapeutic agents produces enhanced cytotoxicity on esophageal carcinoma.Cancer Gene Ther. 2014 Jan;21(1):31-7. doi: 10.1038/cgt.2013.79. Epub 2014 Jan 17.
• [9] Interleukin-20 targets podocytes and is upregulated in experimental murine diabetic nephropathy.Exp Mol Med. 2017 Mar 31;49(3):e310. doi: 10.1038/emm.2016.169.
• [10] mda-7/IL-24 expression inhibits breast cancer through upregulation of growth arrest-specific gene 3 (gas3) and disruption of 1 integrin function.Mol Cancer Res. 2013 Jun;11(6):593-603. doi: 10.1158/1541-7786.MCR-12-0496. Epub 2013 Mar 6.
• [11] The Interleukin-20 Cytokine Family in Liver Disease.Front Immunol. 2018 May 28;9:1155. doi: 10.3389/fimmu.2018.01155. eCollection 2018.
• [12] Promotion of osteoclastogenesis by IL-26 in rheumatoid arthritis.Arthritis Res Ther. 2019 Dec 12;21(1):283. doi: 10.1186/s13075-019-2070-0.
• [13] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [14] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [15] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [16] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [17] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [18] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.