Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6RG1OZ)

• DOT Name: UPF0450 protein C17orf58 (C17ORF58)
• Gene Name: C17ORF58
• Related Disease: Non-insulin dependent diabetes
• UniProt ID: CQ058_HUMAN
• Sequence:
  MTARAFWLLCLIVGSSPEAPVAERKTSPPHSRKPDSRGCPSAEETPGPRAQPLLEAPQRP
  RAAEVAPAARAWPDPRRRKPPPPADNQASFREAARAPAGPPGPRLAQAENRASPRREPAS
  EDAPRRARSRALRFPAARPPALATEGSAGHAHPNRPRAAALAPGPAPAPPPRFSLSFGLS
  PPQRDAEPGAEPCARACRSDLDEREAFCESEFAVNGIVHDVDVLGAGIRLVTLLVDRDGL
  YKMNRLYLTPDGFFFRVHMLALDSSSCNKPCPEFKPGSRYIVMGHIYHKRRQLPTALLQV
  LRGRLRPGDGLLRSSSSYVKRFNRKREGQIQGAIHTQCI

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of UPF0450 protein C17orf58 (C17ORF58).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of UPF0450 protein C17orf58 (C17ORF58).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of UPF0450 protein C17orf58 (C17ORF58).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of UPF0450 protein C17orf58 (C17ORF58).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of UPF0450 protein C17orf58 (C17ORF58).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of UPF0450 protein C17orf58 (C17ORF58).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of UPF0450 protein C17orf58 (C17ORF58).	[8]

References

• [1] Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.Nat Genet. 2018 Apr;50(4):559-571. doi: 10.1038/s41588-018-0084-1. Epub 2018 Apr 9.
• [2] 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.
• [3] 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.
• [4] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [5] 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.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.