Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFRD9RI)

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 9; GalNAc-T9; pp-GaNTase 9; Protein-UDP acetylgalactosaminyltransferase 9; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 9
• Gene Name: GALNT9
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
  Neuroblastoma
• UniProt ID: GALT9_HUMAN
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MAVARKIRTLLTVNILVFVGIVLFSVYCRLQGRSQELVRIVSGDRRVRSRHAKVGTLGDR
  EAILQRLDHLEEVVYNQLNGLAKPIGLVEGPGGLGQGGLAATLRDDGQEAEGKYEEYGYN
  AQLSDRISLDRSIPDYRPRKCRQMSYAQDLPQVSVVFIFVNEALSVILRSVHSVVNHTPS
  QLLKEVILVDDNSDNVELKFNLDQYVNKRYPGLVKIVRNSRREGLIRARLQGWKAATAPV
  VGFFDAHVEFNTGWAEPALSRIREDRRRIVLPAIDNIKYSTFEVQQYANAAHGYNWGLRC
  MYIIPPQDWLDRGDESAPIRTPAMIGCSFVVDREYFGDIGLLDPGMEVYGGENVELGMRV
  WQCGGSMEVLPCSRVAHIERTRKPYNNDIDYYAKRNALRAAEVWMDDFKSHVYMAWNIPM
  SNPGVDFGDVSERLALRQRLKCRSFKWYLENVYPEMRVYNNTLTYGEVRNSKASAYCLDQ
  GAEDGDRAILYPCHGMSSQLVRYSADGLLQLGPLGSTAFLPDSKCLVDDGTGRMPTLKKC
  EDVARPTQRLWDFTQSGPIVSRATGRCLEVEMSKDANFGLRLVVQRCSGQKWMIRNWIKH
  ARH
• Function: Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Does not glycosylate apomucin or SDC3.
• Tissue Specificity: Specifically expressed in brain. Not expressed in heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocyte. In brain, it is expressed in cerebellum, frontal lobe, temporal lobe, putamen and spinal cord, weakly expressed in cerebral cortex. Not expressed in medulla and occipital pole.
• KEGG Pathway:
  Mucin type O-glycan biosynthesis (hsa00512)
  Other types of O-glycan biosynthesis (hsa00514)
  Metabolic pathways (hsa01100)
• Reactome Pathway: O-linked glycosylation of mucins (R-HSA-913709)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[2]

4 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 Polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9).	[9]

References

• [1] Body mass index, diet, and exercise: testing possible linkages to breast cancer risk via DNA methylation.Breast Cancer Res Treat. 2018 Feb;168(1):241-248. doi: 10.1007/s10549-017-4573-1. Epub 2017 Nov 10.
• [2] GALNT9 gene expression is a prognostic marker in neuroblastoma patients.Clin Chem. 2013 Jan;59(1):225-33. doi: 10.1373/clinchem.2012.192328. Epub 2012 Nov 7.
• [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] 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] 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.
• [6] 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.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] 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.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] 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.