Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAFFAE8)

• DOT Name: N-acetylgalactosamine-6-sulfatase (GALNS)
• Synonyms: EC 3.1.6.4; Chondroitinsulfatase; Chondroitinase; Galactose-6-sulfate sulfatase; GalN6S; N-acetylgalactosamine-6-sulfate sulfatase; GalNAc6S sulfatase
• Gene Name: GALNS
• Related Disease: Mucopolysaccharidosis type 4A
• UniProt ID: GALNS_HUMAN
• PDB ID: 4FDI; 4FDJ
• EC Number: 3.1.6.4
• Pfam ID: PF00884 ; PF14707
• Sequence:
  MAAVVAATRWWQLLLVLSAAGMGASGAPQPPNILLLLMDDMGWGDLGVYGEPSRETPNLD
  RMAAEGLLFPNFYSANPLCSPSRAALLTGRLPIRNGFYTTNAHARNAYTPQEIVGGIPDS
  EQLLPELLKKAGYVSKIVGKWHLGHRPQFHPLKHGFDEWFGSPNCHFGPYDNKARPNIPV
  YRDWEMVGRYYEEFPINLKTGEANLTQIYLQEALDFIKRQARHHPFFLYWAVDATHAPVY
  ASKPFLGTSQRGRYGDAVREIDDSIGKILELLQDLHVADNTFVFFTSDNGAALISAPEQG
  GSNGPFLCGKQTTFEGGMREPALAWWPGHVTAGQVSHQLGSIMDLFTTSLALAGLTPPSD
  RAIDGLNLLPTLLQGRLMDRPIFYYRGDTLMAATLGQHKAHFWTWTNSWENFRQGIDFCP
  GQNVSGVTTHNLEDHTKLPLIFHLGRDPGERFPLSFASAEYQEALSRITSVVQQHQEALV
  PAQPQLNVCNWAVMNWAPPGCEKLGKCLTPPESIPKKCLWSH
• KEGG Pathway:
  Glycosaminoglycan degradation (hsa00531)
  Metabolic pathways (hsa01100)
  Lysosome (hsa04142)
• Reactome Pathway:
  MPS IV - Morquio syndrome A (R-HSA-2206290)
  Neutrophil degranulation (R-HSA-6798695)
  Keratan sulfate degradation (R-HSA-2022857)
• BioCyc Pathway: MetaCyc:HS06790-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mucopolysaccharidosis type 4A	DISTYFQS	Definitive	Autosomal recessive	[1]

2 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 N-acetylgalactosamine-6-sulfatase (GALNS).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of N-acetylgalactosamine-6-sulfatase (GALNS).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of N-acetylgalactosamine-6-sulfatase (GALNS).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of N-acetylgalactosamine-6-sulfatase (GALNS).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of N-acetylgalactosamine-6-sulfatase (GALNS).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of N-acetylgalactosamine-6-sulfatase (GALNS).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of N-acetylgalactosamine-6-sulfatase (GALNS).	[8]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of N-acetylgalactosamine-6-sulfatase (GALNS).	[9]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] 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.
• [9] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.