Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2PC1E1)

• DOT Name: Voltage-dependent calcium channel gamma-6 subunit (CACNG6)
• Synonyms: Neuronal voltage-gated calcium channel gamma-6 subunit
• Gene Name: CACNG6
• Related Disease:
  Acute myocardial infarction
  Asthma
  Cardiac failure
  Congestive heart failure
  Schizophrenia
• UniProt ID: CCG6_HUMAN
• Pfam ID: PF13903
• Sequence:
  MMWSNFFLQEENRRRGAAGRRRAHGQGRSGLTPEREGKVKLALLLAAVGATLAVLSVGTE
  FWVELNTYKANGSAVCEAAHLGLWKACTKRLWQADVPVDRDTCGPAELPGEANCTYFKFF
  TTGENARIFQRTTKKEVNLAAAVIAVLGLAVMALGCLCIIMVLSKGAEFLLRVGAVCFGL
  SGLLLLVSLEVFRHSVRALLQRVSPEPPPAPRLTYEYSWSLGCGVGAGLILLLGAGCFLL
  LTLPSWPWGSLCPKRGHRAT
• Function: Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit.
• Tissue Specificity: Detected in heart left ventricle.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Cardiac muscle contraction (hsa04260)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Oxytocin sig.ling pathway (hsa04921)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Phase 2 - plateau phase (R-HSA-5576893)
  Phase 0 - rapid depolarisation (R-HSA-5576892)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[1]
Asthma	DISW9QNS	Strong	Genetic Variation	[2]
Cardiac failure	DISDC067	Strong	Biomarker	[3]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Biomarker	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Voltage-dependent calcium channel gamma-6 subunit (CACNG6) affects the response to substance of Aspirin.	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Voltage-dependent calcium channel gamma-6 subunit (CACNG6).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Voltage-dependent calcium channel gamma-6 subunit (CACNG6).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Voltage-dependent calcium channel gamma-6 subunit (CACNG6).	[5]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Voltage-dependent calcium channel gamma-6 subunit (CACNG6).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Voltage-dependent calcium channel gamma-6 subunit (CACNG6).	[9]

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 decreases the methylation of Voltage-dependent calcium channel gamma-6 subunit (CACNG6).	[8]

References

• [1] Identification of Transcription Factor-Gene Regulatory Network in Acute Myocardial Infarction.Heart Lung Circ. 2017 Apr;26(4):343-353. doi: 10.1016/j.hlc.2016.06.1209. Epub 2016 Jul 26.
• [2] Association of CACNG6 polymorphisms with aspirin-intolerance asthmatics in a Korean population. BMC Med Genet. 2010 Sep 23;11:138. doi: 10.1186/1471-2350-11-138.
• [3] RETRACTED ARTICLE: Inhibition of miR-296-5p protects the heart from cardiac hypertrophy by targeting CACNG6.Gene Ther. 2021 Jun;28(6):391. doi: 10.1038/s41434-019-0109-0. Epub 2019 Dec 16.
• [4] Evaluation of voltage-dependent calcium channel gene families identified several novel potential susceptible genes to schizophrenia.Sci Rep. 2016 Apr 22;6:24914. doi: 10.1038/srep24914.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [8] 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.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] Association of CACNG6 polymorphisms with aspirin-intolerance asthmatics in a Korean population. BMC Med Genet. 2010 Sep 23;11:138. doi: 10.1186/1471-2350-11-138.