Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOM9C4A)

• DOT Name: Cytochrome c oxidase assembly factor 8 (COA8)
• Synonyms: COA8; Apoptogenic protein 1, mitochondrial; APOP-1
• Gene Name: COA8
• Related Disease:
  Cytochrome-c oxidase deficiency disease
  Mitochondrial disease
  Leukodystrophy
  Mitochondrial complex 4 deficiency, nuclear type 17
  Schizophrenia
  Non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy
  Erectile dysfunction
• UniProt ID: COA8_HUMAN
• Pfam ID: PF10231
• Sequence:
  MLPCAAGARGRGAMVVLRAGKKTFLPPLCRAFACRGCQLAPERGAERRDTAPSGVSRFCP
  PRKSCHDWIGPPDKYSNLRPVHFYIPENESPLEQKLRKLRQETQEWNQQFWANQNLTFSK
  EKEEFIHSRLKTKGLGLRTESGQKATLNAEEMADFYKEFLSKNFQKHMYYNRDWYKRNFA
  ITFFMGKVALERIWNKLKQKQKKRSN
• Function: Required for cytochrome c complex (COX) IV assembly and function Protects COX assembly from oxidation-induced degradation, COX being the terminal component of the mitochondrial respiratory chain.
• Tissue Specificity: Expressed in fibroblasts.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cytochrome-c oxidase deficiency disease	DISK7N3G	Definitive	Autosomal recessive	[1]
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[2]
Leukodystrophy	DISVY1TT	Strong	Genetic Variation	[3]
Mitochondrial complex 4 deficiency, nuclear type 17	DISB5I6G	Strong	Autosomal recessive	[4]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[5]
Non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy	DISQHT28	Supportive	Autosomal recessive	[4]
Erectile dysfunction	DISD8MTH	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cytochrome c oxidase assembly factor 8 (COA8).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cytochrome c oxidase assembly factor 8 (COA8).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cytochrome c oxidase assembly factor 8 (COA8).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cytochrome c oxidase assembly factor 8 (COA8).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cytochrome c oxidase assembly factor 8 (COA8).	[12]

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 affects the methylation of Cytochrome c oxidase assembly factor 8 (COA8).	[11]

References

• [1] Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects. Am J Hum Genet. 2016 Sep 1;99(3):770-776. doi: 10.1016/j.ajhg.2016.07.009.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Cavitating Leukoencephalopathy With Posterior Predominance Caused by a Deletion in the APOPT1 Gene in an Indian Boy.J Child Neurol. 2018 May;33(6):428-431. doi: 10.1177/0883073818760875. Epub 2018 Mar 26.
• [4] Mutations in APOPT1, encoding a mitochondrial protein, cause cavitating leukoencephalopathy with cytochrome c oxidase deficiency. Am J Hum Genet. 2014 Sep 4;95(3):315-25. doi: 10.1016/j.ajhg.2014.08.003. Epub 2014 Aug 28.
• [5] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [6] Optimization of the APOP screener to predict functional decline or mortality in older emergency department patients: Cross-validation in four prospective cohorts.Exp Gerontol. 2018 Sep;110:253-259. doi: 10.1016/j.exger.2018.06.015. Epub 2018 Jun 20.
• [7] 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.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] 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.