Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMGH9OA)

• DOT Name: Transmembrane protein 208 (TMEM208)
• Gene Name: TMEM208
• Related Disease:
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
• UniProt ID: TM208_HUMAN
• Pfam ID: PF05620
• Sequence:
  MAPKGKVGTRGKKQIFEENRETLKFYLRIILGANAIYCLVTLVFFYSSASFWAWLALGFS
  LAVYGASYHSMSSMARAAFSEDGALMDGGMDLNMEQGMAEHLKDVILLTAIVQVLSCFSL
  YVWSFWLLAPGRALYLLWVNVLGPWFTADSGTPAPEHNEKRQRRQERRQMKRL
• Function: May function as a negative regulator of endoplasmic reticulum-stress induced autophagy.
• KEGG Pathway: Protein export (hsa03060)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]

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 Transmembrane protein 208 (TMEM208).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Transmembrane protein 208 (TMEM208).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 208 (TMEM208).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transmembrane protein 208 (TMEM208).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Transmembrane protein 208 (TMEM208).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transmembrane protein 208 (TMEM208).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transmembrane protein 208 (TMEM208).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Transmembrane protein 208 (TMEM208).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Transmembrane protein 208 (TMEM208).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 208 (TMEM208).	[10]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Transmembrane protein 208 (TMEM208).	[11]

References

• [1] Identification of TMEM208 and PQLC2 as reference genes for normalizing mRNA expression in colorectal cancer treated with aspirin.Oncotarget. 2017 Apr 4;8(14):22759-22771. doi: 10.18632/oncotarget.15191.
• [2] 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.
• [3] 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.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [8] 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.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.