Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6OCR3H)

• DOT Name: Voltage-dependent calcium channel gamma-1 subunit (CACNG1)
• Synonyms: Dihydropyridine-sensitive L-type, skeletal muscle calcium channel subunit gamma
• Gene Name: CACNG1
• Related Disease: Postmenopausal osteoporosis
• UniProt ID: CCG1_HUMAN
• Pfam ID: PF13903
• Sequence:
  MSQTKMLKVRVTLFCILAGIVLAMTAVVTDHWAVLSPHMEHHNTTCEAAHFGLWRICTKR
  IPMDDSKTCGPITLPGEKNCSYFRHFNPGESSEIFEFTTQKEYSISAAAIAIFSLGFIIL
  GSLCVLLSLGKKRDYLLRPASMFYAFAGLCILVSVEVMRQSVKRMIDSEDTVWIEYYYSW
  SFACACAAFILLFLGGLALLLFSLPRMPRNPWESCMDAEPEH
• Function: Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Regulates channel inactivation kinetics.
• Tissue Specificity: Skeletal muscle.
• 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

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Postmenopausal osteoporosis	DISS0RQZ	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Voltage-dependent calcium channel gamma-1 subunit (CACNG1).	[2]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Voltage-dependent calcium channel gamma-1 subunit (CACNG1).	[3]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Voltage-dependent calcium channel gamma-1 subunit (CACNG1).	[4]

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 affects the methylation of Voltage-dependent calcium channel gamma-1 subunit (CACNG1).	[5]

References

• [1] In silico analysis of the molecular mechanism of postmenopausal osteoporosis.Mol Med Rep. 2015 Nov;12(5):6584-90. doi: 10.3892/mmr.2015.4283. Epub 2015 Sep 2.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [4] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [5] 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.