Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY21FKV)

• DOT Name: Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L)
• Synonyms: COX7a-related protein; Cytochrome c oxidase subunit VIIa-related protein; EB1
• Gene Name: COX7A2L
• Related Disease:
  Nephropathy
  Breast cancer
  Breast carcinoma
  Familial adenomatous polyposis
  Neoplasm
  Pulmonary embolism
  Stroke
  Ulcerative colitis
  Venous thromboembolism
  Endometrial cancer
  Endometrial carcinoma
  Squamous cell carcinoma
  Advanced cancer
• UniProt ID: COX7R_HUMAN
• Pfam ID: PF02238
• Sequence:
  MYYKFSGFTQKLAGAWASEAYSPQGLKPVVSTEAPPIIFATPTKLTSDSTVYDYAGKNKV
  PELQKFFQKADGVPVYLKRGLPDQMLYRTTMALTVGGTIYCLIALYMASQPKNK
• Function: Involved in the regulation of oxidative phosphorylation and energy metabolism. Necessary for the assembly of mitochondrial respiratory supercomplex.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Cardiac muscle contraction (hsa04260)
  Thermogenesis (hsa04714)
  Non-alcoholic fatty liver disease (hsa04932)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Respiratory electron transport (R-HSA-611105)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Pulmonary embolism	DISJYP9B	Strong	Genetic Variation	[5]
Stroke	DISX6UHX	Strong	Genetic Variation	[5]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[6]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[5]
Endometrial cancer	DISW0LMR	moderate	Biomarker	[2]
Endometrial carcinoma	DISXR5CY	moderate	Biomarker	[2]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[7]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[8]

13 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 subunit 7A-related protein, mitochondrial (COX7A2L).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[15]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[16]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[17]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[18]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[19]
Daidzein	DMRFTJX	Investigative	Daidzein increases the expression of Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L).	[13]

References

• [1] The genetic background difference between diabetic patients with and without nephropathy in a Taiwanese population by linkage disequilibrium mapping using 382 autosomal STR markers.Genet Test Mol Biomarkers. 2010 Jun;14(3):433-8. doi: 10.1089/gtmb.2009.0179.
• [2] Mitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance.Nat Commun. 2019 Sep 11;10(1):4108. doi: 10.1038/s41467-019-12124-6.
• [3] Absence of somatic alterations of the EB1 gene adenomatous polyposis coli-associated protein in human sporadic colorectal cancers.Br J Cancer. 1998 Nov;78(10):1356-60. doi: 10.1038/bjc.1998.684.
• [4] Clinical relevance of cytoskeleton associated proteins for ovarian cancer.J Cancer Res Clin Oncol. 2018 Nov;144(11):2195-2205. doi: 10.1007/s00432-018-2710-9. Epub 2018 Aug 9.
• [5] Genome-wide association analysis of self-reported events in 6135 individuals and 252 827 controls identifies 8 loci associated with thrombosis.Hum Mol Genet. 2016 May 1;25(9):1867-74. doi: 10.1093/hmg/ddw037. Epub 2016 Feb 9.
• [6] EB1 protein alteration characterizes sporadic but not ulcerative colitis associated colorectal cancer.Oncotarget. 2017 Jul 4;8(33):54939-54950. doi: 10.18632/oncotarget.18978. eCollection 2017 Aug 15.
• [7] End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.Clin Chim Acta. 2016 Aug 1;459:45-52. doi: 10.1016/j.cca.2016.05.012. Epub 2016 May 18.
• [8] COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy.Sci Rep. 2016 Aug 23;6:31742. doi: 10.1038/srep31742.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] 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.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Phytoestrogens activate estrogen receptor beta1 and estrogenic responses in human breast and bone cancer cell lines. Mol Nutr Food Res. 2007 Feb;51(2):171-7. doi: 10.1002/mnfr.200600091.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [16] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [17] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [18] In vitro gene expression data supporting a DNA non-reactive genotoxic mechanism for ochratoxin A. Toxicol Appl Pharmacol. 2007 Apr 15;220(2):216-24.
• [19] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.