Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT05BKVP)

• DOT Name: Probable polypeptide N-acetylgalactosaminyltransferase 8 (GALNT8)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 8; GalNAc-T8; pp-GaNTase 8; Protein-UDP acetylgalactosaminyltransferase 8; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 8
• Gene Name: GALNT8
• Related Disease:
  Cryohydrocytosis
  Hepatitis C virus infection
  Autosomal dominant hypophosphatemic rickets
  Metabolic disorder
• UniProt ID: GALT8_HUMAN
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MMFWRKLPKALFIGLTLAIAVNLLLVFSSKGTLQNLFTGGLHRELPLHLNKRYGAVIKRL
  SHLEVELQDLKESMKLALRQQENVNSTLKRAKDEVRPLLKAMETKVNETKKHKTQMKLFP
  HSQLFRQWGEDLSEAQQKAAQDLFRKFGYNAYLSNQLPLNRTIPDTRDYRCLRKTYPSQL
  PSLSVILIFVNEALSIIQRAITSIINRTPSRLLKEIILVDDFSSNGELKVHLDEKIKLYN
  QKYPGLLKIIRHPERKGLAQARNTGWEAATADVVAILDAHIEVNVGWAEPILARIQEDRT
  VIVSPVFDNIRFDTFKLDKYELAVDGFNWELWCRYDALPQAWIDLHDVTAPVKSPSIMGI
  LAANRHFLGEIGSLDGGMLIYGGENVELSLRVWQCGGKVEILPCSRIAHLERHHKPYALD
  LTAALKRNALRVAEIWMDEHKHMVYLAWNIPLQNSGIDFGDVSSRMALREKLKCKTFDWY
  LKNVYPLLKPLHTIVGYGRMKNLLDENVCLDQGPVPGNTPIMYYCHEFSSQNVYYHLTGE
  LYVGQLIAEASASDRCLTDPGKAEKPTLEPCSKAAKNRLHIYWDFKPGGAVINRDTKRCL
  EMKKDLLGSHVLVLQTCSTQVWEIQHTVRDWGQTNSQ
• Function: Probably 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.
• Tissue Specificity: Widely expressed. Expressed in heart, skeletal muscle, kidney, liver, small intestine and placenta. Weakly expressed in colon, thymus, spleen, lung and leukocyte.
• 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
Cryohydrocytosis	DISMQHL3	Strong	Genetic Variation	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[2]
Autosomal dominant hypophosphatemic rickets	DISG799S	Disputed	Biomarker	[3]
Metabolic disorder	DIS71G5H	Disputed	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Probable polypeptide N-acetylgalactosaminyltransferase 8 (GALNT8).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Probable polypeptide N-acetylgalactosaminyltransferase 8 (GALNT8).	[6]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Probable polypeptide N-acetylgalactosaminyltransferase 8 (GALNT8).	[5]

References

• [1] Single-nucleotide polymorphisms in GALNT8 are associated with the response to interferon therapy for chronic hepatitis C.J Gen Virol. 2013 Jan;94(Pt 1):81-89. doi: 10.1099/vir.0.044396-0. Epub 2012 Oct 3.
• [2] Predictive potential of IL-18 -607 and osteopontin -442 polymorphism in interferon-based therapy of HCV infection in the Pakistani population.Viral Immunol. 2014 Oct;27(8):404-11. doi: 10.1089/vim.2014.0044. Epub 2014 Sep 8.
• [3] Molecular cloning of a novel human UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, GalNAc-T8, and analysis as a candidate autosomal dominant hypophosphatemic rickets (ADHR) gene.Gene. 2000 Apr 4;246(1-2):347-56. doi: 10.1016/s0378-1119(00)00050-0.
• [4] 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.
• [5] 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.
• [6] 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.