Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL2W9M5)

• DOT Name: Oviduct-specific glycoprotein (OVGP1)
• Synonyms: Estrogen-dependent oviduct protein; Mucin-9; Oviductal glycoprotein; Oviductin
• Gene Name: OVGP1
• Related Disease:
  Tubular aggregate myopathy
  Advanced cancer
  Epithelial ovarian cancer
  Laryngitis
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Pneumoconiosis
  Uveitis
  Endometrium neoplasm
  Idiopathic interstitial pneumonia
• UniProt ID: OVGP1_HUMAN
• Pfam ID: PF00704
• Sequence:
  MWKLLLWVGLVLVLKHHDGAAHKLVCYFTNWAHSRPGPASILPHDLDPFLCTHLIFAFAS
  MNNNQIVAKDLQDEKILYPEFNKLKERNRELKTLLSIGGWNFGTSRFTTMLSTFANREKF
  IASVISLLRTHDFDGLDLFFLYPGLRGSPMHDRWTFLFLIEELLFAFRKEALLTMRPRLL
  LSAAVSGVPHIVQTSYDVRFLGRLLDFINVLSYDLHGSWERFTGHNSPLFSLPEDPKSSA
  YAMNYWRKLGAPSEKLIMGIPTYGRTFRLLKASKNGLQARAIGPASPGKYTKQEGFLAYF
  EICSFVWGAKKHWIDYQYVPYANKGKEWVGYDNAISFSYKAWFIRREHFGGAMVWTLDMD
  DVRGTFCGTGPFPLVYVLNDILVRAEFSSTSLPQFWLSSAVNSSSTDPERLAVTTAWTTD
  SKILPPGGEAGVTEIHGKCENMTITPRGTTVTPTKETVSLGKHTVALGEKTEITGAMTMT
  SVGHQSMTPGEKALTPVGHQSVTTGQKTLTSVGYQSVTPGEKTLTPVGHQSVTPVSHQSV
  SPGGTTMTPVHFQTETLRQNTVAPRRKAVAREKVTVPSRNISVTPEGQTMPLRGENLTSE
  VGTHPRMGNLGLQMEAENRMMLSSSPVIQLPEQTPLAFDNRFVPIYGNHSSVNSVTPQTS
  PLSLKKEIPENSAVDEEA
• Function: Binds to oocyte zona pellucida in vivo. May play a role in the fertilization process and/or early embryonic development.
• Tissue Specificity: Oviduct.
• Reactome Pathway: Interaction With Cumulus Cells And The Zona Pellucida (R-HSA-2534343)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tubular aggregate myopathy	DISC11WH	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Laryngitis	DISX7UUD	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Pneumoconiosis	DISSJLBN	Strong	Biomarker	[6]
Uveitis	DISV0RYS	Strong	Biomarker	[7]
Endometrium neoplasm	DIS6OS2L	Limited	Biomarker	[8]
Idiopathic interstitial pneumonia	DISH7LPY	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Oviduct-specific glycoprotein (OVGP1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Oviduct-specific glycoprotein (OVGP1).	[17]

10 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 Oviduct-specific glycoprotein (OVGP1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Oviduct-specific glycoprotein (OVGP1).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Oviduct-specific glycoprotein (OVGP1).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Oviduct-specific glycoprotein (OVGP1).	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of Oviduct-specific glycoprotein (OVGP1).	[15]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Oviduct-specific glycoprotein (OVGP1).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Oviduct-specific glycoprotein (OVGP1).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Oviduct-specific glycoprotein (OVGP1).	[18]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Oviduct-specific glycoprotein (OVGP1).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Oviduct-specific glycoprotein (OVGP1).	[20]

References

• [1] Lineage tracing suggests that ovarian endosalpingiosis does not result from escape of oviductal epithelium.J Pathol. 2019 Oct;249(2):206-214. doi: 10.1002/path.5308. Epub 2019 Jul 8.
• [2] Useful genetic variation databases for oncologists investigating the genetic basis of variable treatment response and survival in cancer.Acta Oncol. 2010 Nov;49(8):1217-26. doi: 10.3109/0284186X.2010.500297. Epub 2010 Jul 29.
• [3] Cross-validation of genes potentially associated with overall survival and drug resistance in ovarian cancer.Oncol Rep. 2017 May;37(5):3084-3092. doi: 10.3892/or.2017.5534. Epub 2017 Mar 27.
• [4] Mucin gene expression in human laryngeal epithelia: effect of laryngopharyngeal reflux.Ann Otol Rhinol Laryngol. 2008 Sep;117(9):688-95. doi: 10.1177/000348940811700911.
• [5] Tubal Origin of "Ovarian" Low-Grade Serous Carcinoma: A Gene Expression Profile Study.J Oncol. 2019 Mar 5;2019:8659754. doi: 10.1155/2019/8659754. eCollection 2019.
• [6] Pathway analysis for a genome-wide association study of pneumoconiosis.Toxicol Lett. 2015 Jan 5;232(1):284-92. doi: 10.1016/j.toxlet.2014.10.028. Epub 2014 Nov 4.
• [7] Iontophoretic Dexamethasone Phosphate Compared to Topical Prednisolone Acetate 1% for Noninfectious Anterior Segment Uveitis.Am J Ophthalmol. 2020 Mar;211:76-86. doi: 10.1016/j.ajo.2019.10.032. Epub 2019 Nov 11.
• [8] Gain of OGP, an estrogen-regulated oviduct-specific glycoprotein, is associated with the development of endometrial hyperplasia and endometrial cancer.Clin Cancer Res. 2004 Dec 1;10(23):7958-64. doi: 10.1158/1078-0432.CCR-04-1261.
• [9] Unique expression profiles of mucin proteins in interstitial pneumonia-associated lung adenocarcinomas.Histol Histopathol. 2019 Nov;34(11):1243-1254. doi: 10.14670/HH-18-114. Epub 2019 Apr 9.
• [10] 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.
• [11] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Progesterone inhibits insulin-like growth factor binding protein-1 (IGFBP-1) production by explants of the Fallopian tube. Mol Hum Reprod. 2004 Dec;10(12):935-9. doi: 10.1093/molehr/gah124. Epub 2004 Oct 22.
• [14] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [15] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [16] Histamine H4 receptor agonists have more activities than H4 agonism in antigen-specific human T-cell responses. Immunology. 2007 Jun;121(2):266-75. doi: 10.1111/j.1365-2567.2007.02574.x. Epub 2007 Mar 7.
• [17] 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.
• [18] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [19] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [20] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.