Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT85J32K)

• DOT Name: Normal mucosa of esophagus-specific gene 1 protein (C15ORF48)
• Synonyms: Protein FOAP-11
• Gene Name: C15ORF48
• Related Disease:
  Esophageal squamous cell carcinoma
  Advanced cancer
  Intrahepatic cholangiocarcinoma
  Neoplasm
  Non-small-cell lung cancer
  Squamous cell carcinoma
• UniProt ID: NMES1_HUMAN
• Pfam ID: PF06522
• Sequence:
  MSFFQLLMKRKELIPLVVFMTVAAGGASSFAVYSLWKTDVILDRKKNPEPWETVDPTVPQ
  KLITINQQWKPIEELQNVQRVTK
• Tissue Specificity: Expressed mainly in stomach, placenta, small intestine and colon, as well as in normal mucosa of esophagus. Down-regulated in esophageal squamous cell carcinoma.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[4]

19 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 Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[11]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[12]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[13]
Bosentan	DMIOGBU	Approved	Bosentan affects the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[15]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[16]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[17]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[21]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[22]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Normal mucosa of esophagus-specific gene 1 protein (C15ORF48).	[23]

References

• [1] Analysis of the methylation status of genes up-regulated by the demethylating agent, 5-aza-2'-deoxycytidine, in esophageal squamous cell carcinoma.Oncol Rep. 2008 Aug;20(2):405-12.
• [2] Discovery of novel methylation biomarkers in cervical carcinoma by global demethylation and microarray analysis.Cancer Epidemiol Biomarkers Prev. 2006 Jan;15(1):114-23. doi: 10.1158/1055-9965.EPI-05-0323.
• [3] Hypermethylation of normal mucosa of esophagus-specific 1 is associated with an unfavorable prognosis in patients with non-small cell lung cancer.Oncol Lett. 2018 Aug;16(2):2409-2415. doi: 10.3892/ol.2018.8915. Epub 2018 Jun 6.
• [4] Differentiating cutaneous squamous cell carcinoma and pseudoepitheliomatous hyperplasia by multiplex qRT-PCR.Mod Pathol. 2013 Nov;26(11):1433-7. doi: 10.1038/modpathol.2013.82. Epub 2013 May 24.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [8] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [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 effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [11] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [12] 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.
• [13] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [14] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [15] 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.
• [16] Resveratrol inhibits pancreatic cancer cell proliferation through transcriptional induction of macrophage inhibitory cytokine-1. J Surg Res. 2007 Apr;138(2):163-9. doi: 10.1016/j.jss.2006.05.037. Epub 2007 Jan 25.
• [17] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [18] Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses. J Biol Chem. 2015 Oct 16;290(42):25322-32. doi: 10.1074/jbc.M115.645234. Epub 2015 Aug 20.
• [19] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [20] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [23] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.