Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN4PGI5)

• DOT Name: Voltage-dependent calcium channel gamma-5 subunit (CACNG5)
• Synonyms: Neuronal voltage-gated calcium channel gamma-5 subunit; Transmembrane AMPAR regulatory protein gamma-5; TARP gamma-5
• Gene Name: CACNG5
• Related Disease:
  Parkinson disease
  Bipolar disorder
  Schizophrenia
• UniProt ID: CCG5_HUMAN
• Pfam ID: PF13903
• Sequence:
  MSACGRKALTLLSSVFAVCGLGLLGIAVSTDYWLYLEEGVIVPQNQSTEIKMSLHSGLWR
  VCFLAGEERGRCFTIEYVMPMNTQLTSESTVNVLKMIRSATPFPLVSLFFMFIGFILNNI
  GHIRPHRTILAFVSGIFFILSGLSLVVGLVLYISSINDEMLNRTKDAETYFNYKYGWSFA
  FAAISFLLTESAGVMSVYLFMKRYTAEDMYRPHPGFYRPRLSNCSDYSGQFLHPDAWVRG
  RSPSDISSEASLQMNSNYPALLKCPDYDQMSSSPC
• Function: Regulates the gating properties of AMPA-selective glutamate receptors (AMPARs). Modulates their gating properties by accelerating their rates of activation, deactivation and desensitization. Displays subunit-specific AMPA receptor regulation. Shows specificity for GRIA1, GRIA4 and the long isoform of GRIA2. Thought to stabilize the calcium channel in an inactivated (closed) state.
• 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)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Definitive	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Voltage-dependent calcium channel gamma-5 subunit (CACNG5).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Voltage-dependent calcium channel gamma-5 subunit (CACNG5).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Voltage-dependent calcium channel gamma-5 subunit (CACNG5).	[5]

References

• [1] Suppressed microRNA-96 inhibits iNOS expression and dopaminergic neuron apoptosis through inactivating the MAPK signaling pathway by targeting CACNG5 in mice with Parkinson's disease.Mol Med. 2018 Nov 28;24(1):61. doi: 10.1186/s10020-018-0059-9.
• [2] Case-case genome-wide association analysis shows markers differentially associated with schizophrenia and bipolar disorder and implicates calcium channel genes.Psychiatr Genet. 2011 Feb;21(1):1-4. doi: 10.1097/YPG.0b013e3283413382.
• [3] 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.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [6] 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.