Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI0JAT8)

• DOT Name: TPA-induced transmembrane protein (C3ORF52)
• Gene Name: C3ORF52
• Related Disease: Hypotrichosis 15
• UniProt ID: TTMP_HUMAN
• Sequence:
  MDLAQPSQPVDELELSVLERQPEENTPLNGADKVFPSLDEEVPPAEANKESPWSSCNKNV
  VGRCKLWMIITSIFLGVITVIIIGLCLAAVTYVDEDENEILELSSNKTFFIMLKIPEECV
  AEEELPHLLTERLTDVYSTSPSLGRYFTSVEIVDFSGENATVTYDLQFGVPSDDENFMKY
  MMSEELVLGILLQDFRDQNIPGCESLGLDPTSLLLYE
• Function: Has a role in LIPH-mediated synthesis of 2-acyl lysophosphatidic acid (LPA). LPA is a bioactive lipid mediator involved in different biological processes, and necessary to promote hair formation and growth.
• Tissue Specificity: Detected predominantly in the skin, with strongest expression in the inner root sheath of the hair follicle.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypotrichosis 15	DIS74M00	Strong	Autosomal recessive	[1]

19 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 TPA-induced transmembrane protein (C3ORF52).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of TPA-induced transmembrane protein (C3ORF52).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TPA-induced transmembrane protein (C3ORF52).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of TPA-induced transmembrane protein (C3ORF52).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of TPA-induced transmembrane protein (C3ORF52).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of TPA-induced transmembrane protein (C3ORF52).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of TPA-induced transmembrane protein (C3ORF52).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of TPA-induced transmembrane protein (C3ORF52).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of TPA-induced transmembrane protein (C3ORF52).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of TPA-induced transmembrane protein (C3ORF52).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of TPA-induced transmembrane protein (C3ORF52).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of TPA-induced transmembrane protein (C3ORF52).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of TPA-induced transmembrane protein (C3ORF52).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of TPA-induced transmembrane protein (C3ORF52).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of TPA-induced transmembrane protein (C3ORF52).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of TPA-induced transmembrane protein (C3ORF52).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of TPA-induced transmembrane protein (C3ORF52).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of TPA-induced transmembrane protein (C3ORF52).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of TPA-induced transmembrane protein (C3ORF52).	[18]

References

• [1] Loss-of-function variants in C3ORF52 result in localized autosomal recessive hypotrichosis. Genet Med. 2020 Jul;22(7):1227-1234. doi: 10.1038/s41436-020-0794-5. Epub 2020 Apr 27.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [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] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.