Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO8J1D0)

• DOT Name: Sorting nexin-7 (SNX7)
• Gene Name: SNX7
• Related Disease:
  Non-insulin dependent diabetes
  Bipolar disorder
  Psychotic disorder
• UniProt ID: SNX7_HUMAN
• PDB ID: 3IQ2
• Pfam ID: PF00787
• Sequence:
  MDMNSFSPMMPTSPLSMINQIKFEDEPDLKDLFITVDEPESHVTTIETFITYRIITKTSR
  GEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKGMVERFNDDFIETRRKA
  LHKFLNRIADHPTLTFNEDFKIFLTAQAWELSSHKKQGPGLLSRMGQTVRAVASSMRGVK
  NRPEEFMEMNNFIELFSQKINLIDKISQRIYKEEREYFDEMKEYGPIHILWSASEEDLVD
  TLKDVASCIDRCCKATEKRMSGLSEALLPVVHEYVLYSEMLMGVMKRRDQIQAELDSKVE
  VLTYKKADTDLLPEEIGKLEDKVECANNALKADWERWKQNMQNDIKLAFTDMAEENIHYY
  EQCLATWESFLTSQTNLHLEEASEDKP
• Function: Involved in the regulation of endocytosis and in several stages of intracellular trafficking. Together with SNX4, involved in autophagosome assembly by regulating trafficking and recycling of phospholipid scramblase ATG9A.

Molecular Interaction Atlas (MIA) of This DOT

3 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]
Bipolar disorder	DISAM7J2	Limited	Altered Expression	[2]
Psychotic disorder	DIS4UQOT	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sorting nexin-7 (SNX7).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sorting nexin-7 (SNX7).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sorting nexin-7 (SNX7).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Sorting nexin-7 (SNX7).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sorting nexin-7 (SNX7).	[8]

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 decreases the methylation of Sorting nexin-7 (SNX7).	[7]

References

• [1] Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes.Clin Pharmacol Ther. 2018 Apr;103(4):712-721. doi: 10.1002/cpt.798. Epub 2017 Nov 3.
• [2] The kynurenine pathway in schizophrenia and bipolar disorder.Neuropharmacology. 2017 Jan;112(Pt B):297-306. doi: 10.1016/j.neuropharm.2016.05.020. Epub 2016 May 28.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.