Details of Drug Off-Target (DOT)

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

• DOT Name: Transmembrane protein 230 (TMEM230)
• Gene Name: TMEM230
• Related Disease:
  Late-onset Parkinson disease
  Parkinson disease
  Alzheimer disease
  Lewy body dementia
  Young-onset Parkinson disease
• UniProt ID: TM230_HUMAN
• Pfam ID: PF05915
• Sequence:
  MMPSRTNLATGIPSSKVKYSRLSSTDDGYIDLQFKKTPPKIPYKAIALATVLFLIGAFLI
  IIGSLLLSGYISKGGADRAVPVLIIGILVFLPGFYHLRIAYYASKGYRGYSYDDIPDFDD
• Function: Involved in trafficking and recycling of synaptic vesicles.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Late-onset Parkinson disease	DIS9IOUI	Strong	Biomarker	[1]
Parkinson disease	DISQVHKL	Moderate	Semidominant	[2]
Alzheimer disease	DISF8S70	Limited	Biomarker	[3]
Lewy body dementia	DISAE66J	Limited	Biomarker	[3]
Young-onset Parkinson disease	DIS05LFS	Limited	Genetic Variation	[4]

9 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 Transmembrane protein 230 (TMEM230).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 230 (TMEM230).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 230 (TMEM230).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transmembrane protein 230 (TMEM230).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Transmembrane protein 230 (TMEM230).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transmembrane protein 230 (TMEM230).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transmembrane protein 230 (TMEM230).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Transmembrane protein 230 (TMEM230).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Transmembrane protein 230 (TMEM230).	[15]

3 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 increases the methylation of Transmembrane protein 230 (TMEM230).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Transmembrane protein 230 (TMEM230).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Transmembrane protein 230 (TMEM230).	[11]

References

• [1] TMEM230: How does it fit in the etiology and pathogenesis of Parkinson's disease?.Mov Disord. 2017 Aug;32(8):1159-1162. doi: 10.1002/mds.27061. Epub 2017 Jun 1.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] TMEM230 Accumulation in Granulovacuolar Degeneration Bodies and Dystrophic Neurites of Alzheimer's Disease.J Alzheimers Dis. 2017;58(4):1027-1033. doi: 10.3233/JAD-170190.
• [4] Screening for TMEM230 mutations in young-onset Parkinson's disease.Neurobiol Aging. 2017 Oct;58:239.e9-239.e10. doi: 10.1016/j.neurobiolaging.2017.06.011. Epub 2017 Jun 24.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] 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.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.