Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK12EG7)

• DOT Name: Cytochrome c oxidase assembly factor 5 (COA5)
• Gene Name: COA5
• Related Disease:
  Cardiomyopathy
  Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3
  Cytochrome-c oxidase deficiency disease
  Hypertrophic cardiomyopathy
• UniProt ID: COA5_HUMAN
• Pfam ID: PF10203
• Sequence:
  MPKYYEDKPQGGACAGLKEDLGACLLQSDCVVQEGKSPRQCLKEGYCNSLKYAFFECKRS
  VLDNRARFRGRKGY
• Function: Involved in an early step of the mitochondrial complex IV assembly process.
• KEGG Pathway: Thermogenesis (hsa04714)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[1]
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3	DIS5FF5P	Limited	Unknown	[2]
Cytochrome-c oxidase deficiency disease	DISK7N3G	Limited	Autosomal recessive	[3]
Hypertrophic cardiomyopathy	DISQG2AI	Limited	Biomarker	[1]

7 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 Cytochrome c oxidase assembly factor 5 (COA5).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytochrome c oxidase assembly factor 5 (COA5).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cytochrome c oxidase assembly factor 5 (COA5).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Cytochrome c oxidase assembly factor 5 (COA5).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Cytochrome c oxidase assembly factor 5 (COA5).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cytochrome c oxidase assembly factor 5 (COA5).	[9]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Cytochrome c oxidase assembly factor 5 (COA5).	[10]

References

• [1] A mutation in C2orf64 causes impaired cytochrome c oxidase assembly and mitochondrial cardiomyopathy.Am J Hum Genet. 2011 Apr 8;88(4):488-93. doi: 10.1016/j.ajhg.2011.03.002. Epub 2011 Mar 31.
• [2] Accuracy of measures of temporomandibular joint space and condylar position with three tomographic imaging techniques. Oral Surg Oral Med Oral Pathol. 1991 Sep;72(3):364-70. doi: 10.1016/0030-4220(91)90234-4.
• [3] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.