Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAXFAA2)

• DOT Name: Vacuolar ATPase assembly integral membrane protein VMA21
• Synonyms: Myopathy with excessive autophagy protein
• Gene Name: VMA21
• Related Disease: X-linked myopathy with excessive autophagy
• UniProt ID: VMA21_HUMAN
• Pfam ID: PF09446
• Sequence:
  MERPDKAALNALQPPEFRNESSLASTLKTLLFFTALMITVPIGLYFTTKSYIFEGALGMS
  NRDSYFYAAIVAVVAVHVVLALFVYVAWNEGSRQWREGKQD
• Function: Required for the assembly of the V0 complex of the vacuolar ATPase (V-ATPase) in the endoplasmic reticulum.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
X-linked myopathy with excessive autophagy	DIS1AFQH	Strong	X-linked	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Vacuolar ATPase assembly integral membrane protein VMA21.	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Vacuolar ATPase assembly integral membrane protein VMA21.	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Vacuolar ATPase assembly integral membrane protein VMA21.	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Vacuolar ATPase assembly integral membrane protein VMA21.	[5]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Vacuolar ATPase assembly integral membrane protein VMA21.	[6]

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 Vacuolar ATPase assembly integral membrane protein VMA21.	[7]

References

• [1] A new congenital form of X-linked autophagic vacuolar myopathy. Neurology. 2005 Oct 11;65(7):1132-4. doi: 10.1212/01.wnl.0000178979.19887.f5.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [7] 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.