Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8NR7GC)

DOT Name Glypican-5 (GPC5)
Gene Name GPC5
Related Disease
Neural tube defect ( )
Cardiac arrest ( )
Epithelial ovarian cancer ( )
Glioma ( )
Hepatocellular carcinoma ( )
Hereditary hemochromatosis ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Malignant soft tissue neoplasm ( )
Narcolepsy ( )
Neoplasm ( )
Neuromyelitis optica ( )
Non-small-cell lung cancer ( )
Overgrowth syndrome ( )
Prostate cancer ( )
Prostate carcinoma ( )
Rhabdomyosarcoma ( )
Rheumatoid arthritis ( )
Sarcoma ( )
Severe combined immunodeficiency ( )
Simpson-Golabi-Behmel syndrome ( )
Simpson-Golabi-Behmel syndrome type 1 ( )
Tourette syndrome ( )
Nephrotic syndrome ( )
Non-insulin dependent diabetes ( )
Pancreatic cancer ( )
Lymphoma ( )
Matthew-Wood syndrome ( )
Multiple sclerosis ( )
Pancreatic ductal carcinoma ( )
Tetralogy of fallot ( )
UniProt ID
GPC5_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF01153
Sequence
MDAQTWPVGFRCLLLLALVGSARSEGVQTCEEVRKLFQWRLLGAVRGLPDSPRAGPDLQV
CISKKPTCCTRKMEERYQIAARQDMQQFLQTSSSTLKFLISRNAAAFQETLETLIKQAEN
YTSILFCSTYRNMALEAAASVQEFFTDVGLYLFGADVNPEEFVNRFFDSLFPLVYNHLIN
PGVTDSSLEYSECIRMARRDVSPFGNIPQRVMGQMGRSLLPSRTFLQALNLGIEVINTTD
YLHFSKECSRALLKMQYCPHCQGLALTKPCMGYCLNVMRGCLAHMAELNPHWHAYIRSLE
ELSDAMHGTYDIGHVLLNFHLLVNDAVLQAHLNGQKLLEQVNRICGRPVRTPTQSPRCSF
DQSKEKHGMKTTTRNSEETLANRRKEFINSLRLYRSFYGGLADQLCANELAAADGLPCWN
GEDIVKSYTQRVVGNGIKAQSGNPEVKVKGIDPVINQIIDKLKHVVQLLQGRSPKPDKWE
LLQLGSGGGMVEQVSGDCDDEDGCGGSGSGEVKRTLKITDWMPDDMNFSDVKQIHQTDTG
STLDTTGAGCAVATESMTFTLISVVMLLPGIW
Function Cell surface proteoglycan that bears heparan sulfate.
Tissue Specificity In adult, primarily expressed in the brain. Also detected in fetal brain, lung and liver.
Reactome Pathway
HS-GAG biosynthesis (R-HSA-2022928 )
HS-GAG degradation (R-HSA-2024096 )
Defective B4GALT7 causes EDS, progeroid type (R-HSA-3560783 )
Defective B3GAT3 causes JDSSDHD (R-HSA-3560801 )
Defective EXT2 causes exostoses 2 (R-HSA-3656237 )
Defective EXT1 causes exostoses 1, TRPS2 and CHDS (R-HSA-3656253 )
Defective B3GALT6 causes EDSP2 and SEMDJL1 (R-HSA-4420332 )
Release of Hh-Np from the secreting cell (R-HSA-5362798 )
Attachment and Entry (R-HSA-9694614 )
Retinoid metabolism and transport (R-HSA-975634 )
A tetrasaccharide linker sequence is required for GAG synthesis (R-HSA-1971475 )

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neural tube defect DIS5J95E Definitive Altered Expression [1]
Cardiac arrest DIS9DIA4 Strong Genetic Variation [2]
Epithelial ovarian cancer DIS56MH2 Strong Genetic Variation [3]
Glioma DIS5RPEH Strong Altered Expression [4]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [5]
Hereditary hemochromatosis DISVG5MT Strong Biomarker [6]
Lung adenocarcinoma DISD51WR Strong Altered Expression [7]
Lung cancer DISCM4YA Strong Biomarker [8]
Lung carcinoma DISTR26C Strong Biomarker [8]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [6]
Narcolepsy DISLCNLI Strong Genetic Variation [9]
Neoplasm DISZKGEW Strong Biomarker [4]
Neuromyelitis optica DISBFGKL Strong Genetic Variation [10]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [11]
Overgrowth syndrome DISHK54G Strong Biomarker [12]
Prostate cancer DISF190Y Strong Biomarker [13]
Prostate carcinoma DISMJPLE Strong Biomarker [13]
Rhabdomyosarcoma DISNR7MS Strong Biomarker [14]
Rheumatoid arthritis DISTSB4J Strong Genetic Variation [15]
Sarcoma DISZDG3U Strong Biomarker [6]
Severe combined immunodeficiency DIS6MF4Q Strong Altered Expression [8]
Simpson-Golabi-Behmel syndrome DIS9H9TY Strong Biomarker [12]
Simpson-Golabi-Behmel syndrome type 1 DISYV73N Strong Biomarker [12]
Tourette syndrome DISX9D54 Strong Genetic Variation [16]
Nephrotic syndrome DISSPSC2 moderate Biomarker [17]
Non-insulin dependent diabetes DISK1O5Z moderate Biomarker [18]
Pancreatic cancer DISJC981 moderate Biomarker [19]
Lymphoma DISN6V4S Limited Altered Expression [20]
Matthew-Wood syndrome DISA7HR7 Limited Altered Expression [21]
Multiple sclerosis DISB2WZI Limited Genetic Variation [22]
Pancreatic ductal carcinoma DIS26F9Q Limited Biomarker [21]
Tetralogy of fallot DISMHFNW Limited Genetic Variation [23]
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⏷ Show the Full List of 32 Disease(s)
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
Daunorubicin DMQUSBT Approved Glypican-5 (GPC5) affects the response to substance of Daunorubicin. [33]
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3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Glypican-5 (GPC5). [24]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Glypican-5 (GPC5). [30]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Glypican-5 (GPC5). [31]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Glypican-5 (GPC5). [25]
Triclosan DMZUR4N Approved Triclosan increases the expression of Glypican-5 (GPC5). [26]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Glypican-5 (GPC5). [27]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Glypican-5 (GPC5). [28]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 increases the expression of Glypican-5 (GPC5). [29]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Glypican-5 (GPC5). [32]
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⏷ Show the Full List of 6 Drug(s)

References

1 Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene.Hum Mol Genet. 2013 Mar 15;22(6):1097-111. doi: 10.1093/hmg/dds515. Epub 2012 Dec 7.
2 Genetic markers of repolarization and arrhythmic events after acute coronary syndromes.Am Heart J. 2015 Apr;169(4):579-86.e3. doi: 10.1016/j.ahj.2014.11.015. Epub 2014 Dec 11.
3 Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk.Genet Epidemiol. 2015 Dec;39(8):689-97. doi: 10.1002/gepi.21921. Epub 2015 Sep 24.
4 MicroRNA-301b promotes the proliferation and invasion of glioma cells through enhancing activation of Wnt/-catenin signaling via targeting Glypican-5.Eur J Pharmacol. 2019 Jul 5;854:39-47. doi: 10.1016/j.ejphar.2019.03.057. Epub 2019 Apr 3.
5 miR-709 up-regulated in hepatocellular carcinoma, promotes proliferation and invasion by targeting GPC5.Cell Prolif. 2015 Jun;48(3):330-7. doi: 10.1111/cpr.12181. Epub 2015 Mar 27.
6 Transcriptional Dynamics of Immortalized Human Mesenchymal Stem Cells during Transformation.PLoS One. 2015 May 15;10(5):e0126562. doi: 10.1371/journal.pone.0126562. eCollection 2015.
7 miR-297 acts as an oncogene by targeting GPC5 in lung adenocarcinoma.Cell Prolif. 2016 Oct;49(5):636-43. doi: 10.1111/cpr.12288. Epub 2016 Aug 24.
8 Glypican-5 suppresses Epithelial-Mesenchymal Transition of the lung adenocarcinoma by competitively binding to Wnt3a.Oncotarget. 2016 Nov 29;7(48):79736-79746. doi: 10.18632/oncotarget.12945.
9 Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
10 Putative association of GPC5 polymorphism with the risk of inflammatory demyelinating diseases.J Neurol Sci. 2013 Dec 15;335(1-2):82-8. doi: 10.1016/j.jns.2013.08.031. Epub 2013 Aug 30.
11 Glypican-5 is a novel metastasis suppressor gene in non-small cell lung cancer.Cancer Lett. 2013 Dec 1;341(2):265-73. doi: 10.1016/j.canlet.2013.08.020. Epub 2013 Aug 17.
12 An interstitial duplication of chromosome 13q31.3q32.1 further delineates the critical region for postaxial polydactyly type A2.Eur J Med Genet. 2010 Jan-Feb;53(1):45-9. doi: 10.1016/j.ejmg.2009.11.003. Epub 2009 Nov 23.
13 Overexpression of Glypican 5 (GPC5) Inhibits Prostate Cancer Cell Proliferation and Invasion via Suppressing Sp1-Mediated EMT and Activation of Wnt/-Catenin Signaling.Oncol Res. 2018 May 7;26(4):565-572. doi: 10.3727/096504017X15044461944385. Epub 2017 Sep 6.
14 The role of glypicans in Hedgehog signaling.Matrix Biol. 2014 Apr;35:248-52. doi: 10.1016/j.matbio.2013.12.007. Epub 2014 Jan 8.
15 Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.Hum Mol Genet. 2019 Mar 1;28(5):858-874. doi: 10.1093/hmg/ddy395.
16 Whole-Genome Sequencing of Cytogenetically Balanced Chromosome Translocations Identifies Potentially Pathological Gene Disruptions and Highlights the Importance of Microhomology in the Mechanism of Formation.Hum Mutat. 2017 Feb;38(2):180-192. doi: 10.1002/humu.23146. Epub 2016 Dec 5.
17 The Accumulation of Heparan Sulfate S-Domains in Kidney Transthyretin Deposits Accelerates Fibril Formation and Promotes Cytotoxicity.Am J Pathol. 2019 Feb;189(2):308-319. doi: 10.1016/j.ajpath.2018.09.015. Epub 2018 Nov 7.
18 Levels and Clinical Significances of Glypican-5 in Urine of Type 2 Diabetic Nephropathy Cases.Iran J Kidney Dis. 2019 May;13(3):173-181.
19 Genome-wide association study using diversity outcross mice identified candidate genes of pancreatic cancer.Genomics. 2019 Dec;111(6):1882-1888. doi: 10.1016/j.ygeno.2018.12.011. Epub 2018 Dec 20.
20 GPC5 is a possible target for the 13q31-q32 amplification detected in lymphoma cell lines.J Hum Genet. 2003;48(6):331-335. doi: 10.1007/s10038-003-0026-2. Epub 2003 Apr 29.
21 High expression of microRNA-4295 contributes to cell proliferation and invasion of pancreatic ductal adenocarcinoma by the down-regulation of Glypican-5.Biochem Biophys Res Commun. 2018 Feb 26;497(1):73-79. doi: 10.1016/j.bbrc.2018.02.023. Epub 2018 Feb 3.
22 Prediction of response to interferon therapy in multiple sclerosis.Acta Neurol Scand. 2014 Oct;130(4):268-75. doi: 10.1111/ane.12269. Epub 2014 Jun 18.
23 Genome-wide association study identifies loci on 12q24 and 13q32 associated with tetralogy of Fallot.Hum Mol Genet. 2013 Apr 1;22(7):1473-81. doi: 10.1093/hmg/dds552. Epub 2013 Jan 7.
24 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.
25 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
26 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
27 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
28 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
29 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
30 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.
31 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.
32 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.
33 Mapping genes that contribute to daunorubicin-induced cytotoxicity. Cancer Res. 2007 Jun 1;67(11):5425-33. doi: 10.1158/0008-5472.CAN-06-4431.