Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBS3YWY)

• DOT Name: Ion channel TACAN (TMEM120A)
• Synonyms: Transmembrane protein 120A; Transmembrane protein induced by tumor necrosis factor alpha
• Gene Name: TMEM120A
• UniProt ID: TACAN_HUMAN
• PDB ID: 7CXR; 7F3T; 7F3U; 7F6V; 7N7P
• Pfam ID: PF07851
• Sequence:
  MQPPPPGPLGDCLRDWEDLQQDFQNIQETHRLYRLKLEELTKLQNNCTSSITRQKKRLQE
  LALALKKCKPSLPAEAEGAAQELENQMKERQGLFFDMEAYLPKKNGLYLSLVLGNVNVTL
  LSKQAKFAYKDEYEKFKLYLTIILILISFTCRFLLNSRVTDAAFNFLLVWYYCTLTIRES
  ILINNGSRIKGWWVFHHYVSTFLSGVMLTWPDGLMYQKFRNQFLSFSMYQSFVQFLQYYY
  QSGCLYRLRALGERHTMDLTVEGFQSWMWRGLTFLLPFLFFGHFWQLFNALTLFNLAQDP
  QCKEWQVLMCGFPFLLLFLGNFFTTLRVVHHKFHSQRHGSKKD
• Function: Ion channel involved in sensing mechanical pain. Contributes to mechanosensitive currents in nocireceptors and detecting mechanical pain stimuli. May also be required for efficient adipogenesis.
• Tissue Specificity: Expressed in nociceptors.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ion channel TACAN (TMEM120A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ion channel TACAN (TMEM120A).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ion channel TACAN (TMEM120A).	[3]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Ion channel TACAN (TMEM120A).	[4]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Ion channel TACAN (TMEM120A).	[5]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Ion channel TACAN (TMEM120A).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ion channel TACAN (TMEM120A).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ion channel TACAN (TMEM120A).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ion channel TACAN (TMEM120A).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ion channel TACAN (TMEM120A).	[9]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] 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.
• [4] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [5] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [6] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.