Details of Drug Off-Target (DOT)

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

• DOT Name: Mitochondrial potassium channel (CCDC51)
• Synonyms: MITOK; Coiled-coil domain-containing protein 51
• Gene Name: CCDC51
• Related Disease:
  Adult lymphoma
  Advanced cancer
  Kidney failure
  leukaemia
  Leukemia
  Lymphoma
  Pediatric lymphoma
  Pancreatic ductal carcinoma
• UniProt ID: MITOK_HUMAN
• Sequence:
  MMGRSPGFAMQHIVGVPHVLVRRGLLGRDLFMTRTLCSPGPSQPGEKRPEEVALGLHHRL
  PALGRALGHSIQQRATSTAKTWWDRYEEFVGLNEVREAQGKVTEAEKVFMVARGLVREAR
  EDLEVHQAKLKEVRDRLDRVSREDSQYLELATLEHRMLQEEKRLRTAYLRAEDSEREKFS
  LFSAAVRESHEKERTRAERTKNWSLIGSVLGALIGVAGSTYVNRVRLQELKALLLEAQKG
  PVSLQEAIREQASSYSRQQRDLHNLMVDLRGLVHAAGPGQDSGSQAGSPPTRDRDVDVLS
  AALKEQLSHSRQVHSCLEGLREQLDGLEKTCSQMAGVVQLVKSAAHPGLVEPADGAMPSF
  LLEQGSMILALSDTEQRLEAQVNRNTIYSTLVTCVTFVATLPVLYMLFKAS
• Function: Mitochondrial potassium channel located in the mitochondrial inner membrane. Together with ABCB8/MITOSUR, forms a protein complex localized in the mitochondria that mediates ATP-dependent potassium currents across the inner membrane (that is, mitoK(ATP) channel). May contribute to the homeostatic control of cellular metabolism under stress conditions by regulating the mitochondrial matrix volume.
• Tissue Specificity: Isoform 1: Widely expressed . Isoform 2: Expression is barely detectable .

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Kidney failure	DISOVQ9P	Strong	Biomarker	[2]
leukaemia	DISS7D1V	Strong	Biomarker	[1]
Leukemia	DISNAKFL	Strong	Biomarker	[1]
Lymphoma	DISN6V4S	Strong	Biomarker	[1]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[1]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[3]

13 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 Mitochondrial potassium channel (CCDC51).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitochondrial potassium channel (CCDC51).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial potassium channel (CCDC51).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial potassium channel (CCDC51).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Mitochondrial potassium channel (CCDC51).	[8]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Mitochondrial potassium channel (CCDC51).	[8]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Mitochondrial potassium channel (CCDC51).	[8]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Mitochondrial potassium channel (CCDC51).	[8]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Mitochondrial potassium channel (CCDC51).	[8]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Mitochondrial potassium channel (CCDC51).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Mitochondrial potassium channel (CCDC51).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Mitochondrial potassium channel (CCDC51).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Mitochondrial potassium channel (CCDC51).	[12]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Mitochondrial potassium channel (CCDC51).	[10]

References

• [1] Targeting a mitochondrial potassium channel to fight cancer.Cell Calcium. 2015 Jul;58(1):131-8. doi: 10.1016/j.ceca.2014.09.006. Epub 2014 Oct 18.
• [2] Nicorandil attenuates neuronal mitochondrial dysfunction and oxidative stress associated with murine model of vascular calcification.Acta Neurobiol Exp (Wars). 2017;77(1):57-67. doi: 10.21307/ane-2017-036.
• [3] Regulation of Proliferation by a Mitochondrial Potassium Channel in Pancreatic Ductal Adenocarcinoma Cells.Front Oncol. 2017 Sep 29;7:239. doi: 10.3389/fonc.2017.00239. eCollection 2017.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [9] 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.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.