Details of Drug Off-Target (DOT)

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

DOT Name Pleckstrin homology domain-containing family A member 6 (PLEKHA6)
Synonyms PH domain-containing family A member 6; Phosphoinositol 3-phosphate-binding protein 3; PEPP-3
Gene Name PLEKHA6
Related Disease
Langerhans cell histiocytosis ( )
Langerhans cell histiocytosis specific to childhood ( )
Schizophrenia ( )
UniProt ID
PKHA6_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2D9Y; 2YRY
Pfam ID
PF00169
Sequence
MSNKTGGKRPATTNSDIPNHNMVSEVPPERPSVRATRTARKAVAFGKRSHSMKRNPNAPV
TKAGWLFKQASSGVKQWNKRWFVLVDRCLFYYKDEKEESILGSIPLLSFRVAAVQPSDNI
SRKHTFKAEHAGVRTYFFSAESPEEQEAWIQAMGEAARVQIPPAQKSVPQAVRHSHEKPD
SENVPPSKHHQQPPHNSLPKPEPEAKTRGEGDGRGCEKAERRPERPEVKKEPPVKANGLP
AGPEPASEPGSPYPEGPRVPGGGEQPAQPNGWQYHSPSRPGSTAFPSQDGETGGHRRSFP
PRTNPDKIAQRKSSMNQLQQWVNLRRGVPPPEDLRSPSRFYPVSRRVPEYYGPYSSQYPD
DYQYYPPGVRPESICSMPAYDRISPPWALEDKRHAFRNGGGPAYQLREWKEPASYGRQDA
TVWIPSPSRQPVYYDELDAASSSLRRLSLQPRSHSVPRSPSQGSYSRARIYSPVRSPSAR
FERLPPRSEDIYADPAAYVMRRSISSPKVPPYPEVFRDSLHTYKLNEQDTDKLLGKLCEQ
NKVVREQDRLVQQLRAEKESLESALMGTHQELEMFGSQPAYPEKLRHKKDSLQNQLINIR
VELSQATTALTNSTIEYEHLESEVSALHDDLWEQLNLDTQNEVLNRQIQKEIWRIQDVME
GLRKNNPSRGTDTAKHRGGLGPSATYSSNSPASPLSSASLTSPLSPFSLVSGSQGSPTKP
GSNEPKANYEQSKKDPHQTLPLDTPRDISLVPTRQEVEAEKQAALNKVGVVPPRTKSPTD
DEVTPSAVVRRNASGLTNGLSSQERPKSAVFPGEGKVKMSVEEQIDRMRRHQSGSMREKR
RSLQLPASPAPDPSPRPAYKVVRRHRSIHEVDISNLEAALRAEEPGGHAYETPREEIARL
RKMELEPQHYDVDINKELSTPDKVLIPERYIDLEPDTPLSPEELKEKQKKVERIKTLIAK
SSMQNVVPIGEGDSVDVPQDSESQLQEQEKRIEISCALATEASRRGRMLSVQCATPSPPT
SPASPAPPANPLSSESPRGADSSYTMRV
Tissue Specificity Highly expressed in heart, kidney and throughout the brain.
Reactome Pathway
Synthesis of PIPs at the plasma membrane (R-HSA-1660499 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Langerhans cell histiocytosis DISDQSW3 moderate Biomarker [1]
Langerhans cell histiocytosis specific to childhood DIS1C04U moderate Biomarker [1]
Schizophrenia DISSRV2N No Known Unknown [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Arsenic trioxide DM61TA4 Approved Pleckstrin homology domain-containing family A member 6 (PLEKHA6) decreases the response to substance of Arsenic trioxide. [22]
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6 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 Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [3]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [10]
Triclosan DMZUR4N Approved Triclosan increases the methylation of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [17]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [20]
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⏷ Show the Full List of 6 Drug(s)
15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [4]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [7]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [8]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [9]
Quercetin DM3NC4M Approved Quercetin increases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [11]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [12]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [13]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [14]
Testosterone DM7HUNW Approved Testosterone increases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [13]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [16]
Menadione DMSJDTY Approved Menadione affects the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [18]
Lithium chloride DMHYLQ2 Investigative Lithium chloride decreases the expression of Pleckstrin homology domain-containing family A member 6 (PLEKHA6). [21]
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⏷ Show the Full List of 15 Drug(s)

References

1 A novel fusion gene PLEKHA6-NTRK3 in langerhans cell histiocytosis.Int J Cancer. 2019 Jan 1;144(1):117-124. doi: 10.1002/ijc.31636. Epub 2018 Oct 26.
2 De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014 Feb 13;506(7487):179-84. doi: 10.1038/nature12929. Epub 2014 Jan 22.
3 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.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
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 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
9 Profile of estrogen-responsive genes in an estrogen-specific mammary gland outgrowth model. Mol Reprod Dev. 2009 Aug;76(8):733-50. doi: 10.1002/mrd.21041.
10 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
11 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.
12 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.
13 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
14 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
15 Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort. Environ Pollut. 2021 Dec 1;290:118024. doi: 10.1016/j.envpol.2021.118024. Epub 2021 Aug 21.
16 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
17 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.
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 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.
20 Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
21 Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
22 The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.