Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP306N2)

• DOT Name: Transmembrane protein 180 (MFSD13A)
• Synonyms: Major facilitator superfamily domain-containing 13A
• Gene Name: MFSD13A
• Related Disease:
  Neoplasm
  Allergic rhinitis
  Pancreatic cancer
  Ulcerative colitis
  Colorectal carcinoma
• UniProt ID: MF13A_HUMAN
• Pfam ID: PF13347
• Sequence:
  MGLGQPQAWLLGLPTAVVYGSLALFTTILHNVFLLYYVDTFVSVYKINKMAFWVGETVFL
  LWNSLNDPLFGWLSDRQFLSSQPRSGAGLSSRAVVLARVQALGWHGPLLALSFLAFWVPW
  APAGLQFLLCLCLYDGFLTLVDLHHHALLADLALSAHDRTHLNFYCSLFSAAGSLSVFAS
  YAFWNKEDFSSFRAFCVTLAVSSGLGFLGATQLLRRRVEAARKDPGCSGLVVDSGLCGEE
  LLVGSEEADSITLGRYLRQLARHRNFLWFVSMDLVQVFHCHFNSNFFPLFLEHLLSDHIS
  LSTGSILLGLSYVAPHLNNLYFLSLCRRWGVYAVVRGLFLLKLGLSLLMLLAGPDHLSLL
  CLFIASNRVFTEGTCKLLTLVVTDLVDEDLVLNHRKQAASALLFGMVALVTKPGQTFAPL
  LGTWLLCFYTGHDLFQQSLITPVGSAHPWPEPPAPAPAQAPTLRQGCFYLLVLVPITCAL
  LQLFTWSQFTLHGRRLHMVKAQRQNLSQAQTLDVKMV
• Tissue Specificity: Highly expressed in colorectal cancer cell lines but not in the normal colonocytes.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Allergic rhinitis	DIS3U9HN	moderate	Genetic Variation	[2]
Pancreatic cancer	DISJC981	moderate	Genetic Variation	[3]
Ulcerative colitis	DIS8K27O	moderate	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 180 (MFSD13A).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 180 (MFSD13A).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 180 (MFSD13A).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Transmembrane protein 180 (MFSD13A).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transmembrane protein 180 (MFSD13A).	[11]

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 Transmembrane protein 180 (MFSD13A).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transmembrane protein 180 (MFSD13A).	[10]

References

• [1] Significant antitumor effect of an antibody against TMEM180, a new colorectal cancer-specific molecule.Cancer Sci. 2019 Feb;110(2):761-770. doi: 10.1111/cas.13907. Epub 2019 Jan 4.
• [2] Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.Nat Genet. 2018 Aug;50(8):1072-1080. doi: 10.1038/s41588-018-0157-1. Epub 2018 Jul 16.
• [3] A functional variant in the boundary of a topological association domain is associated with pancreatic cancer risk.Mol Carcinog. 2019 Oct;58(10):1855-1862. doi: 10.1002/mc.23077. Epub 2019 Jun 24.
• [4] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.