Details of Drug Off-Target (DOT)

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

• DOT Name: N-acetylglucosamine-6-sulfatase (GNS)
• Synonyms: EC 3.1.6.14; Glucosamine-6-sulfatase; G6S
• Gene Name: GNS
• Related Disease:
  Mucopolysaccharidosis type 3D
  Neoplasm
  Brain neoplasm
  Inherited retinal dystrophy
  Lysosomal storage disease
  Melanoma
  Mucopolysaccharidosis type 3B
  Rheumatoid arthritis
  Mucopolysaccharidosis
  Mucopolysaccharidosis type 3A
  Mucopolysaccharidosis type 3C
  Mucopolysaccharidosis type IIIA
• UniProt ID: GNS_HUMAN
• EC Number: 3.1.6.14
• Pfam ID: PF00884
• Sequence:
  MRLLPLAPGRLRRGSPRHLPSCSPALLLLVLGGCLGVFGVAAGTRRPNVVLLLTDDQDEV
  LGGMTPLKKTKALIGEMGMTFSSAYVPSALCCPSRASILTGKYPHNHHVVNNTLEGNCSS
  KSWQKIQEPNTFPAILRSMCGYQTFFAGKYLNEYGAPDAGGLEHVPLGWSYWYALEKNSK
  YYNYTLSINGKARKHGENYSVDYLTDVLANVSLDFLDYKSNFEPFFMMIATPAPHSPWTA
  APQYQKAFQNVFAPRNKNFNIHGTNKHWLIRQAKTPMTNSSIQFLDNAFRKRWQTLLSVD
  DLVEKLVKRLEFTGELNNTYIFYTSDNGYHTGQFSLPIDKRQLYEFDIKVPLLVRGPGIK
  PNQTSKMLVANIDLGPTILDIAGYDLNKTQMDGMSLLPILRGASNLTWRSDVLVEYQGEG
  RNVTDPTCPSLSPGVSQCFPDCVCEDAYNNTYACVRTMSALWNLQYCEFDDQEVFVEVYN
  LTADPDQITNIAKTIDPELLGKMNYRLMMLQSCSGPTCRTPGVFDPGYRFDPRLMFSNRG
  SVRTRRFSKHLL
• KEGG Pathway:
  Glycosaminoglycan degradation (hsa00531)
  Metabolic pathways (hsa01100)
  Lysosome (hsa04142)
• Reactome Pathway:
  MPS IIID - Sanfilippo syndrome D (R-HSA-2206305)
  Lysosome Vesicle Biogenesis (R-HSA-432720)
  Neutrophil degranulation (R-HSA-6798695)
  Keratan sulfate degradation (R-HSA-2022857)
• BioCyc Pathway: MetaCyc:HS06046-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mucopolysaccharidosis type 3D	DISQUYLN	Definitive	Autosomal recessive	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[3]
Inherited retinal dystrophy	DISGGL77	Strong	Genetic Variation	[4]
Lysosomal storage disease	DIS6QM6U	Strong	Biomarker	[5]
Melanoma	DIS1RRCY	Strong	Biomarker	[6]
Mucopolysaccharidosis type 3B	DIS1RN28	Strong	Biomarker	[7]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[8]
Mucopolysaccharidosis	DISB083T	Limited	Genetic Variation	[9]
Mucopolysaccharidosis type 3A	DIS2TLNF	Limited	Genetic Variation	[10]
Mucopolysaccharidosis type 3C	DISH5D5W	Limited	Genetic Variation	[11]
Mucopolysaccharidosis type IIIA	DISP7DR6	Limited	Biomarker	[5]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ardeparin	DMYRX8B	Approved	N-acetylglucosamine-6-sulfatase (GNS) affects the degradation of Ardeparin.	[7]

13 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 N-acetylglucosamine-6-sulfatase (GNS).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of N-acetylglucosamine-6-sulfatase (GNS).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of N-acetylglucosamine-6-sulfatase (GNS).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of N-acetylglucosamine-6-sulfatase (GNS).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of N-acetylglucosamine-6-sulfatase (GNS).	[16]
Selenium	DM25CGV	Approved	Selenium decreases the expression of N-acetylglucosamine-6-sulfatase (GNS).	[17]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide decreases the expression of N-acetylglucosamine-6-sulfatase (GNS).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of N-acetylglucosamine-6-sulfatase (GNS).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of N-acetylglucosamine-6-sulfatase (GNS).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of N-acetylglucosamine-6-sulfatase (GNS).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of N-acetylglucosamine-6-sulfatase (GNS).	[22]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of N-acetylglucosamine-6-sulfatase (GNS).	[23]
PP-242	DM2348V	Investigative	PP-242 increases the expression of N-acetylglucosamine-6-sulfatase (GNS).	[24]

References

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• [2] An Extendable Star-Like Nanoplatform for Functional and Anatomical Imaging-Guided Photothermal Oncotherapy.ACS Nano. 2019 Apr 23;13(4):4379-4391. doi: 10.1021/acsnano.8b09607. Epub 2019 Mar 26.
• [3] Non-invasive sensitive brain tumor detection using dual-modality bioimaging nanoprobe.Nanotechnology. 2019 Jul 5;30(27):275101. doi: 10.1088/1361-6528/ab0e9c. Epub 2019 Mar 11.
• [4] Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies.Genet Med. 2016 Jun;18(6):554-62. doi: 10.1038/gim.2015.127. Epub 2015 Sep 10.
• [5] Disease correction by AAV-mediated gene therapy in a new mouse model of mucopolysaccharidosis type IIID.Hum Mol Genet. 2017 Apr 15;26(8):1535-1551. doi: 10.1093/hmg/ddx058.
• [6] Precise control of apoptosis via gold nanostars for dose dependent photothermal therapy of melanoma.J Mater Chem B. 2019 Nov 28;7(44):6934-6944. doi: 10.1039/c9tb01956a. Epub 2019 Nov 1.
• [7] Chromosomal localization of the gene for human glucosamine-6-sulphatase to 12q14. Hum Genet. 1988 Jun;79(2):175-8. doi: 10.1007/BF00280560.
• [8] Two rheumatoid arthritis-specific autoantigens correlate microbial immunity with autoimmune responses in joints. J Clin Invest. 2017 Aug 1;127(8):2946-2956.
• [9] How close are we to therapies for Sanfilippo disease?.Metab Brain Dis. 2018 Feb;33(1):1-10. doi: 10.1007/s11011-017-0111-4. Epub 2017 Sep 18.
• [10] Polymorphic variants (p.Ser141Ser and p.Arg737Gly) at the NAGLU gene are really indicative of pseudodeficiency alleles?.Ital J Pediatr. 2019 May 14;45(1):60. doi: 10.1186/s13052-019-0657-3.
• [11] Glycosaminoglycans and mucopolysaccharidosis type III.Front Biosci (Landmark Ed). 2016 Jun 1;21(7):1393-409. doi: 10.2741/4463.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [15] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [18] Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
• [19] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [20] 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.
• [21] 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.
• [22] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [23] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [24] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
• [25] Chromosomal localization of the gene for human glucosamine-6-sulphatase to 12q14. Hum Genet. 1988 Jun;79(2):175-8. doi: 10.1007/BF00280560.