Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFJ62UI)

• DOT Name: Putative transcription factor Ovo-like 1 (OVOL1)
• Synonyms: hOvo1
• Gene Name: OVOL1
• Related Disease:
  Lung squamous cell carcinoma
  Asthma
  B-cell neoplasm
  Cutaneous squamous cell carcinoma
  Epithelial neoplasm
  Gout
  Melanoma
  Squamous cell carcinoma
  Atopic dermatitis
  Nasopharyngeal carcinoma
• UniProt ID: OVOL1_HUMAN
• Pfam ID: PF00096
• Sequence:
  MPRAFLVKKPCVSTCKRNWSELPDEERGEIYVPVSLGFCPPQPYREPEPSVAEPPSCPLA
  LNMSLRDSSYSMAPGPCVVAQLPSEDMGHLTDPQSRDHGFLRTKMKVTLGDSPSGDLFTC
  RVCQKAFTYQRMLNRHMKCHNDVKRHLCTYCGKGFNDTFDLKRHVRTHTGVRPYKCSLCD
  KAFTQRCSLESHLKKIHGVQQKYAYKERRAKLYVCEECGCTSESQEGHVLHLKEHHPDSP
  LLRKTSKKVAVALQNTVTSLLQGSPHL
• Function: Putative transcription factor. Involved in hair formation and spermatogenesis. May function in the differentiation and/or maintenance of the urogenital system.
• Tissue Specificity: Expressed in fetal kidney, and also in adult pancreas and placenta. Not expressed in intestine, peripheral blood lymphocytes and ovary.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung squamous cell carcinoma	DISXPIBD	Definitive	Genetic Variation	[1]
Asthma	DISW9QNS	Strong	Genetic Variation	[2]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[3]
Cutaneous squamous cell carcinoma	DIS3LXUG	Strong	Altered Expression	[4]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[4]
Gout	DISHC0U7	Strong	Genetic Variation	[5]
Melanoma	DIS1RRCY	Strong	Biomarker	[6]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[4]
Atopic dermatitis	DISTCP41	Limited	Biomarker	[7]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Putative transcription factor Ovo-like 1 (OVOL1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Putative transcription factor Ovo-like 1 (OVOL1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Putative transcription factor Ovo-like 1 (OVOL1).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Putative transcription factor Ovo-like 1 (OVOL1).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Putative transcription factor Ovo-like 1 (OVOL1).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Putative transcription factor Ovo-like 1 (OVOL1).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Putative transcription factor Ovo-like 1 (OVOL1).	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Putative transcription factor Ovo-like 1 (OVOL1).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Putative transcription factor Ovo-like 1 (OVOL1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Putative transcription factor Ovo-like 1 (OVOL1).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Putative transcription factor Ovo-like 1 (OVOL1).	[18]

References

• [1] TRIM58/cg26157385 methylation is associated with eight prognostic genes in lung squamous cell carcinoma.Oncol Rep. 2018 Jul;40(1):206-216. doi: 10.3892/or.2018.6426. Epub 2018 May 8.
• [2] Shared genetics of asthma and mental health disorders: a large-scale genome-wide cross-trait analysis.Eur Respir J. 2019 Dec 19;54(6):1901507. doi: 10.1183/13993003.01507-2019. Print 2019 Dec.
• [3] Comparative analysis of testis transcriptomes associated with male infertility in triploid cyprinid fish.Reprod Fertil Dev. 2019 Jan;31(2):248-260. doi: 10.1071/RD18034.
• [4] Potential role of the OVOL1-OVOL2 axis and c-Myc in the progression of cutaneous squamous cell carcinoma.Mod Pathol. 2017 Jul;30(7):919-927. doi: 10.1038/modpathol.2016.169. Epub 2017 Mar 24.
• [5] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
• [6] The role of the OVOL1-OVOL2 axis in normal and diseased human skin.J Dermatol Sci. 2018 Jun;90(3):227-231. doi: 10.1016/j.jdermsci.2018.02.005. Epub 2018 Feb 12.
• [7] The IL-13-OVOL1-FLG axis in atopic dermatitis.Immunology. 2019 Dec;158(4):281-286. doi: 10.1111/imm.13120. Epub 2019 Oct 1.
• [8] Identification of key genes involved in nasopharyngeal carcinoma.Braz J Otorhinolaryngol. 2017 Nov-Dec;83(6):670-676. doi: 10.1016/j.bjorl.2016.09.003. Epub 2016 Sep 26.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [12] 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.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [15] 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.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] The Effects of Combined Exposure to Bisphenols and Perfluoroalkyls on Human Perinatal Stem Cells and the Potential Implications for Health Outcomes. Int J Mol Sci. 2023 Oct 9;24(19):15018. doi: 10.3390/ijms241915018.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.