Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8GOL3T)

• DOT Name: Alpha-1,4-N-acetylglucosaminyltransferase (A4GNT)
• Synonyms: Alpha4GnT; EC 2.4.1.-
• Gene Name: A4GNT
• Related Disease:
  Adenocarcinoma
  Gastric adenocarcinoma
  Pancreatic cancer
  Pancreatic tumour
  Advanced cancer
  Gastric cancer
  Gastritis
  Peptic ulcer
  Stomach cancer
• UniProt ID: A4GCT_HUMAN
• EC Number: 2.4.1.-
• Pfam ID: PF04572 ; PF04488
• Sequence:
  MRKELQLSLSVTLLLVCGFLYQFTLKSSCLFCLPSFKSHQGLEALLSHRRGIVFLETSER
  MEPPHLVSCSVESAAKIYPEWPVVFFMKGLTDSTPMPSNSTYPAFSFLSAIDNVFLFPLD
  MKRLLEDTPLFSWYNQINASAERNWLHISSDASRLAIIWKYGGIYMDTDVISIRPIPEEN
  FLAAQASRYSSNGIFGFLPHHPFLWECMENFVEHYNSAIWGNQGPELMTRMLRVWCKLED
  FQEVSDLRCLNISFLHPQRFYPISYREWRRYYEVWDTEPSFNVSYALHLWNHMNQEGRAV
  IRGSNTLVENLYRKHCPRTYRDLIKGPEGSVTGELGPGNK
• Function: Catalyzes the transfer of N-acetylglucosamine (GlcNAc) to core 2 branched O-glycans. Necessary for the synthesis of type III mucin which is specifically produced in the stomach, duodenum, and pancreatic duct. May protect against inflammation-associated gastric adenocarcinomas.
• Tissue Specificity: Detected in stomach and pancreas.
• Reactome Pathway: O-linked glycosylation of mucins (R-HSA-913709)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[1]
Gastric adenocarcinoma	DISWWLTC	Strong	Biomarker	[2]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[3]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[4]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[4]
Gastritis	DIS8G07K	moderate	Biomarker	[4]
Peptic ulcer	DISL8XZI	moderate	Biomarker	[4]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[4]

1 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 Alpha-1,4-N-acetylglucosaminyltransferase (A4GNT).	[5]

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 Alpha-1,4-N-acetylglucosaminyltransferase (A4GNT).	[6]

References

• [1] Reduced GlcNAc glycosylation on gastric gland mucin is a biomarker of malignant potential for gastric cancer, Barrett's adenocarcinoma, and pancreatic cancer.Histochem Cell Biol. 2018 Jun;149(6):569-575. doi: 10.1007/s00418-018-1667-8. Epub 2018 Apr 16.
• [2] GlcNAc and its catalyst 4GnT are diagnostic and prognostic markers in uterine cervical tumor, gastric type.Sci Rep. 2019 Sep 10;9(1):13043. doi: 10.1038/s41598-019-49376-7.
• [3] Clinical utility of quantitative RT-PCR targeted to alpha1,4-N-acetylglucosaminyltransferase mRNA for detection of pancreatic cancer.Cancer Sci. 2006 Feb;97(2):119-26. doi: 10.1111/j.1349-7006.2006.00148.x.
• [4] Usefulness of the real-time reverse transcription-polymerase chain reaction assay targeted to alpha1,4-N-acetylglucosaminyltransferase for the detection of gastric cancer.Lab Invest. 2003 Feb;83(2):187-97. doi: 10.1097/01.lab.0000057001.21187.a0.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] 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.