Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT45DF7)

• DOT Name: Ly6/PLAUR domain-containing protein 6 (LYPD6)
• Gene Name: LYPD6
• Related Disease:
  Anxiety
  Anxiety disorder
  Tourette syndrome
• UniProt ID: LYPD6_HUMAN
• PDB ID: 6GBI; 6IB6
• Pfam ID: PF16975
• Sequence:
  MEPGPALAWLLLLSLLADCLKAAQSRDFTVKDIIYLHPSTTPYPGGFKCFTCEKAADNYE
  CNRWAPDIYCPRETRYCYTQHTMEVTGNSISVTKRCVPLEECLSTGCRDSEHEGHKVCTS
  CCEGNICNLPLPRNETDATFATTSPINQTNGHPRCMSVIVSCLWLWLGLML
• Function: Acts as a modulator of nicotinic acetylcholine receptors (nAChRs) function in the brain. Inhibits nicotine-induced Ca(2+) influx through nAChRs. In vitro, specifically inhibits alpha-3:beta-4 and alpha-7 nAChR currents in an allosteric manner. Acts as a positive regulator of Wnt/beta-catenin signaling.
• Tissue Specificity: Detected in the temporal cortex (at protein level) . Ubiquitous . Highly expressed in brain and heart .
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Disputed	Biomarker	[1]
Anxiety disorder	DISBI2BT	Disputed	Biomarker	[1]
Tourette syndrome	DISX9D54	No Known	Unknown	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
M710	DM1PRT6	Phase 3	Ly6/PLAUR domain-containing protein 6 (LYPD6) affects the response to substance of M710.	[10]

5 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 Ly6/PLAUR domain-containing protein 6 (LYPD6).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ly6/PLAUR domain-containing protein 6 (LYPD6).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ly6/PLAUR domain-containing protein 6 (LYPD6).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ly6/PLAUR domain-containing protein 6 (LYPD6).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ly6/PLAUR domain-containing protein 6 (LYPD6).	[9]

2 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 Ly6/PLAUR domain-containing protein 6 (LYPD6).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ly6/PLAUR domain-containing protein 6 (LYPD6).	[7]

References

• [1] Loss of Lypd6 leads to reduced anxiety-like behaviour and enhanced responses to nicotine.Prog Neuropsychopharmacol Biol Psychiatry. 2018 Mar 2;82:86-94. doi: 10.1016/j.pnpbp.2017.11.025. Epub 2017 Nov 28.
• [2] [Phenotypic and genotypic analysis of a girl carrying a 2q22.3 microduplication encompassing the MBD5 gene]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2019 Jun 10;36(6):624-627. doi: 10.3760/cma.j.issn.1003-9406.2019.06.024.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [10] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.