Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYG371T)

• DOT Name: Protein odd-skipped-related 2 (OSR2)
• Gene Name: OSR2
• Related Disease:
  Blepharophimosis, ptosis, and epicanthus inversus syndrome
  Female hypogonadism
  Endometriosis
  Cleft palate
  Isolated cleft palate
• UniProt ID: OSR2_HUMAN
• Pfam ID: PF00096
• Sequence:
  MGSKALPAPIPLHPSLQLTNYSFLQAVNTFPATVDHLQGLYGLSAVQTMHMNHWTLGYPN
  VHEITRSTITEMAAAQGLVDARFPFPALPFTTHLFHPKQGAIAHVLPALHKDRPRFDFAN
  LAVAATQEDPPKMGDLSKLSPGLGSPISGLSKLTPDRKPSRGRLPSKTKKEFICKFCGRH
  FTKSYNLLIHERTHTDERPYTCDICHKAFRRQDHLRDHRYIHSKEKPFKCQECGKGFCQS
  RTLAVHKTLHMQESPHKCPTCGRTFNQRSNLKTHLLTHTDIKPYSCEQCGKVFRRNCDLR
  RHSLTHTPRQDF
• Function: May be involved in the development of the mandibular molar tooth germ at the bud stage.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Blepharophimosis, ptosis, and epicanthus inversus syndrome	DISN43YC	Definitive	Biomarker	[1]
Female hypogonadism	DISWASB4	Definitive	Genetic Variation	[1]
Endometriosis	DISX1AG8	Disputed	Biomarker	[2]
Cleft palate	DIS6G5TF	Limited	Genetic Variation	[3]
Isolated cleft palate	DISV80CD	Limited	Genetic Variation	[3]

17 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 Protein odd-skipped-related 2 (OSR2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein odd-skipped-related 2 (OSR2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein odd-skipped-related 2 (OSR2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein odd-skipped-related 2 (OSR2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein odd-skipped-related 2 (OSR2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein odd-skipped-related 2 (OSR2).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein odd-skipped-related 2 (OSR2).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein odd-skipped-related 2 (OSR2).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein odd-skipped-related 2 (OSR2).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein odd-skipped-related 2 (OSR2).	[13]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Protein odd-skipped-related 2 (OSR2).	[2]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Protein odd-skipped-related 2 (OSR2).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein odd-skipped-related 2 (OSR2).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Protein odd-skipped-related 2 (OSR2).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein odd-skipped-related 2 (OSR2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein odd-skipped-related 2 (OSR2).	[19]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Protein odd-skipped-related 2 (OSR2).	[20]

References

• [1] Functional evidence implicating FOXL2 in non-syndromic premature ovarian failure and in the regulation of the transcription factor OSR2.J Med Genet. 2009 Jul;46(7):455-7. doi: 10.1136/jmg.2008.065086. Epub 2009 May 7.
• [2] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [3] Inactivation of Fgfr2 gene in mouse secondary palate mesenchymal cells leads to cleft palate.Reprod Toxicol. 2018 Apr;77:137-142. doi: 10.1016/j.reprotox.2018.03.004. Epub 2018 Mar 8.
• [4] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [8] 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.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [12] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [13] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [14] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [15] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [19] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [20] Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene. 2006 Nov 23;25(55):7311-23.