Details of Drug Off-Target (DOT)

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

• DOT Name: COX assembly mitochondrial protein homolog (CMC1)
• Synonyms: Cmc1p
• Gene Name: CMC1
• Related Disease:
  Arthritis
  Breast carcinoma
  Capillary malformation
  Osteoarthritis
  Ankylosing spondylitis
  Crohn disease
  Psoriasis
  Sclerosing cholangitis
  Synovitis
  Ulcerative colitis
• UniProt ID: COXM1_HUMAN
• Pfam ID: PF08583
• Sequence:
  MALDPADQHLRHVEKDVLIPKIMREKAKERCSEQVQDFTKCCKNSGVLMVVKCRKENSAL
  KECLTAYYNDPAFYEECKMEYLKEREEFRKTGIPTKKRLQKLPTSM
• Function: Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Capillary malformation	DISR6ZSG	Strong	Genetic Variation	[3]
Osteoarthritis	DIS05URM	Strong	Biomarker	[4]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[5]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[5]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[5]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[5]
Synovitis	DISW2GPY	Limited	Genetic Variation	[6]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[5]

6 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 COX assembly mitochondrial protein homolog (CMC1).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of COX assembly mitochondrial protein homolog (CMC1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of COX assembly mitochondrial protein homolog (CMC1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of COX assembly mitochondrial protein homolog (CMC1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of COX assembly mitochondrial protein homolog (CMC1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of COX assembly mitochondrial protein homolog (CMC1).	[13]

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 increases the methylation of COX assembly mitochondrial protein homolog (CMC1).	[12]

References

• [1] Trapeziectomy with LRTI or joint replacement for CMC1 arthritis, a randomised controlled trial.J Plast Surg Hand Surg. 2019 Dec;53(6):361-369. doi: 10.1080/2000656X.2019.1635490. Epub 2019 Jul 4.
• [2] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [3] Capillary malformation-arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations. Am J Hum Genet. 2003 Dec;73(6):1240-9. doi: 10.1086/379793. Epub 2003 Nov 24.
• [4] One-Year Outcomes of Intraarticular Fat Transplantation for Thumb Carpometacarpal Joint Osteoarthritis: Case Review of 99 Joints.Plast Reconstr Surg. 2020 Jan;145(1):151-159. doi: 10.1097/PRS.0000000000006378.
• [5] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [6] Associations Between Ultrasound-Detected Synovitis, Pain, and Function in Interphalangeal and Thumb Base Osteoarthritis: Data From the Nor-Hand Cohort.Arthritis Care Res (Hoboken). 2020 Nov;72(11):1530-1535. doi: 10.1002/acr.24047.
• [7] 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.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] 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.
• [10] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] 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.