Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0HSGML)

• DOT Name: Ly6/PLAUR domain-containing protein 1 (LYPD1)
• Synonyms: Putative HeLa tumor suppressor; PHTS
• Gene Name: LYPD1
• Related Disease:
  Advanced cancer
  Cowden disease
  Familial adenomatous polyposis
  Pendred syndrome
  PTEN hamartoma tumor syndrome
  Autoimmune disease
• UniProt ID: LYPD1_HUMAN
• PDB ID: 6ZSS
• Sequence:
  MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVME
  QSAGIMYRKSCASSAACLIASAGYQSFCSPGKLNSVCISCCNTPLCNGPRPKKRGSSASA
  LRPGLRTTILFLKLALFSAHC
• Function: Believed to act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro increases receptor desensitization and decreases affinity for ACh of alpha-4:beta-2-containing nAChRs. May play a role in the intracellular trafficking of alpha-4:beta-2 and alpha-7-containing nAChRs and may inhibit their expression at the cell surface. May be involved in the control of anxiety.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Cowden disease	DISMYKCE	Strong	Genetic Variation	[2]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[2]
Pendred syndrome	DISZ1MU8	Strong	Genetic Variation	[2]
PTEN hamartoma tumor syndrome	DISR6ULG	Strong	Genetic Variation	[3]
Autoimmune disease	DISORMTM	Limited	Genetic Variation	[3]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[13]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[14]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[20]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Ly6/PLAUR domain-containing protein 1 (LYPD1).	[21]

References

• [1] Unexpected cancer-predisposition gene variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome patients without underlying germline PTEN mutations.PLoS Genet. 2018 Apr 23;14(4):e1007352. doi: 10.1371/journal.pgen.1007352. eCollection 2018 Apr.
• [2] Familial follicular cell tumors: classification and morphological characteristics.Endocr Pathol. 2010 Dec;21(4):219-26. doi: 10.1007/s12022-010-9135-6.
• [3] Immune dysregulation in patients with PTEN hamartoma tumor syndrome: Analysis of FOXP3 regulatory Tcells.J Allergy Clin Immunol. 2017 Feb;139(2):607-620.e15. doi: 10.1016/j.jaci.2016.03.059. Epub 2016 Jun 18.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] 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.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] 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.
• [12] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [13] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [14] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [15] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [16] 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.
• [17] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [18] 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.
• [19] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [20] 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.
• [21] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.