Details of Drug Off-Target (DOT)

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

• DOT Name: Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12)
• Synonyms: EC 2.4.1.41; Polypeptide GalNAc transferase 12; GalNAc-T12; pp-GaNTase 12; Protein-UDP acetylgalactosaminyltransferase 12; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 12
• Gene Name: GALNT12
• Related Disease:
  Adenoma
  Advanced cancer
  Colon cancer
  Colonic neoplasm
  Colorectal neoplasm
  Familial adenomatous polyposis
  Polyposis
  Familial colorectal cancer type X
  Neoplasm
  Colorectal cancer, susceptibility to, 1
• UniProt ID: GLT12_HUMAN
• PDB ID: 6PXU
• EC Number: 2.4.1.41
• Pfam ID: PF00535 ; PF00652
• Sequence:
  MWGRTARRRCPRELRRGREALLVLLALLALAGLGSVLRAQRGAGAGAAEPGPPRTPRPGR
  REPVMPRPPVPANALGARGEAVRLQLQGEELRLQEESVRLHQINIYLSDRISLHRRLPER
  WNPLCKEKKYDYDNLPRTSVIIAFYNEAWSTLLRTVYSVLETSPDILLEEVILVDDYSDR
  EHLKERLANELSGLPKVRLIRANKREGLVRARLLGASAARGDVLTFLDCHCECHEGWLEP
  LLQRIHEEESAVVCPVIDVIDWNTFEYLGNSGEPQIGGFDWRLVFTWHTVPERERIRMQS
  PVDVIRSPTMAGGLFAVSKKYFEYLGSYDTGMEVWGGENLEFSFRIWQCGGVLETHPCSH
  VGHVFPKQAPYSRNKALANSVRAAEVWMDEFKELYYHRNPRARLEPFGDVTERKQLRDKL
  QCKDFKWFLETVYPELHVPEDRPGFFGMLQNKGLTDYCFDYNPPDENQIVGHQVILYLCH
  GMGQNQFFEYTSQKEIRYNTHQPEGCIAVEAGMDTLIMHLCEETAPENQKFILQEDGSLF
  HEQSKKCVQAARKESSDSFVPLLRDCTNSDHQKWFFKERML
• 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. Has activity toward non-glycosylated peptides such as Muc5AC, Muc1a and EA2, and no detectable activity with Muc2 and Muc7. Displays enzymatic activity toward the Gal-NAc-Muc5AC glycopeptide, but no detectable activity to mono-GalNAc-glycosylated Muc1a, Muc2, Muc7 and EA2. May play an important role in the initial step of mucin-type oligosaccharide biosynthesis in digestive organs.
• Tissue Specificity: Widely expressed at different levels of expression. Highly expressed in digestive organs such as small intestine, stomach, pancreas and colon. Expressed at intermediate level in testis, thyroid gland and spleen. Weakly expressed in whole brain, cerebral cortex, cerebellum, fetal brain, bone marrow, thymus, leukocytes, heart, skeletal muscle, liver, lung, esophagus, kidney, adrenal gland, mammary gland, uterus, placenta, ovary and prostate.
• 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)
  Defective GALNT12 causes CRCS1 (R-HSA-5083636)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Colon cancer	DISVC52G	Strong	Genetic Variation	[3]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[4]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[5]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[1]
Polyposis	DISZSPOK	Strong	Biomarker	[1]
Familial colorectal cancer type X	DISEBNIA	Disputed	Biomarker	[6]
Neoplasm	DISZKGEW	Disputed	Genetic Variation	[6]
Colorectal cancer, susceptibility to, 1	DISZ794C	Limited	Autosomal dominant	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[14]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12).	[8]

References

• [1] Role of GALNT12 in the genetic predisposition to attenuated adenomatous polyposis syndrome.PLoS One. 2017 Nov 2;12(11):e0187312. doi: 10.1371/journal.pone.0187312. eCollection 2017.
• [2] Inherited deleterious variants in GALNT12 are associated with CRC susceptibility.Hum Mutat. 2012 Jul;33(7):1056-8. doi: 10.1002/humu.22088. Epub 2012 Apr 9.
• [3] Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers. Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12921-5. doi: 10.1073/pnas.0901454106. Epub 2009 Jul 17.
• [4] Confirmation of linkage to and localization of familial colon cancer risk haplotype on chromosome 9q22.Cancer Res. 2010 Jul 1;70(13):5409-18. doi: 10.1158/0008-5472.CAN-10-0188. Epub 2010 Jun 15.
• [5] Expression of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-12 in gastric and colonic cancer cell lines and in human colorectal cancer.Oncology. 2004;67(3-4):271-6. doi: 10.1159/000081328.
• [6] GALNT12 is not a major contributor of familial colorectal cancer type X.Hum Mutat. 2014 Jan;35(1):50-2. doi: 10.1002/humu.22454. Epub 2013 Oct 17.
• [7] 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.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [9] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [12] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [13] 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.
• [14] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [15] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [16] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [17] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [18] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.