Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKXOH4K)

• DOT Name: Mitochondrial import receptor subunit TOM5 homolog (TOMM5)
• Gene Name: TOMM5
• Related Disease:
  Acute coronary syndrome
  Non-insulin dependent diabetes
• UniProt ID: TOM5_HUMAN
• PDB ID: 7CK6; 7CP9; 7VBY; 7VC4; 7VD2; 7VDD
• Pfam ID: PF10642
• Sequence: MFRIEGLAPKLDPEEMKRKMREDVISSIRNFLIYVALLRVTPFILKKLDSI
• Reactome Pathway:
  PINK1-PRKN Mediated Mitophagy (R-HSA-5205685)
  Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute coronary syndrome	DIS7DYEW	Strong	Genetic Variation	[1]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[2]

11 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 Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[12]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[13]
Okadaic acid	DM47CO1	Investigative	Okadaic acid affects the expression of Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[14]

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 Mitochondrial import receptor subunit TOM5 homolog (TOMM5).	[10]

References

• [1] Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.PLoS One. 2017 Jul 28;12(7):e0182115. doi: 10.1371/journal.pone.0182115. eCollection 2017.
• [2] Identifying candidate genes for Type 2 Diabetes Mellitus and obesity through gene expression profiling in multiple tissues or cells.J Diabetes Res. 2013;2013:970435. doi: 10.1155/2013/970435. Epub 2013 Dec 26.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [7] 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.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
• [14] Alterations in metabolism-related genes induced in SHSY5Y cells by okadaic acid exposure. J Toxicol Environ Health A. 2012;75(13-15):844-56. doi: 10.1080/15287394.2012.690703.