Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB6D21A)

• DOT Name: MICOS complex subunit MIC10 (MICOS10)
• Synonyms: Mitochondrial inner membrane organizing system protein 1
• Gene Name: MICOS10
• Related Disease:
  Advanced cancer
  Hyperthyroidism
  Hypothyroidism
• UniProt ID: MIC10_HUMAN
• Pfam ID: PF04418
• Sequence:
  MSESELGRKWDRCLADAVVKIGTGFGLGIVFSLTFFKRRMWPLAFGSGMGLGMAYSNCQH
  DFQAPYLLHGKYVKEQEQ
• Function: Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane.
• Reactome Pathway: Cristae formation (R-HSA-8949613)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Hyperthyroidism	DISX87ZH	Strong	Genetic Variation	[2]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[3]

10 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 MICOS complex subunit MIC10 (MICOS10).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of MICOS complex subunit MIC10 (MICOS10).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of MICOS complex subunit MIC10 (MICOS10).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of MICOS complex subunit MIC10 (MICOS10).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of MICOS complex subunit MIC10 (MICOS10).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of MICOS complex subunit MIC10 (MICOS10).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of MICOS complex subunit MIC10 (MICOS10).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of MICOS complex subunit MIC10 (MICOS10).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of MICOS complex subunit MIC10 (MICOS10).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of MICOS complex subunit MIC10 (MICOS10).	[12]

References

• [1] Mitochondrial Damage Mediated by miR-1 Overexpression in Cancer Stem Cells.Mol Ther Nucleic Acids. 2019 Dec 6;18:938-953. doi: 10.1016/j.omtn.2019.10.016. Epub 2019 Oct 24.
• [2] Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.Nat Commun. 2018 Oct 26;9(1):4455. doi: 10.1038/s41467-018-06356-1.
• [3] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [10] 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.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.