Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE69HV8)

• DOT Name: N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2)
• Synonyms: EC 2.4.1.149; Beta-1,3-N-acetylglucosaminyltransferase 1; BGnT-1; Beta-1,3-Gn-T1; Beta3Gn-T1; Beta-1,3-galactosyltransferase 7; Beta-1,3-GalTase 7; Beta3Gal-T7; Beta3GalT7; b3Gal-T7; Beta-3-Gx-T7; UDP-Gal:beta-GlcNAc beta-1,3-galactosyltransferase 7; UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 2; BGnT-2; Beta-1,3-Gn-T2; Beta-1,3-N-acetylglucosaminyltransferase 2; Beta3Gn-T2; UDP-galactose:beta-N-acetylglucosamine beta-1,3-galactosyltransferase 7
• Gene Name: B3GNT2
• Related Disease:
  Myocardial infarction
  Ciliopathy
  Dravet syndrome
  Hepatocellular carcinoma
  Muscular dystrophy
  Muscular dystrophy-dystroglycanopathy, type A
  Neoplasm
  Pachyonychia congenita 3
  Pancreatic tumour
  Prostate cancer
  Prostate carcinoma
  Psoriasis
  Rheumatoid arthritis
  Schizophrenia
  Systemic lupus erythematosus
  Transitional cell carcinoma
  Graves disease
  Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13
• UniProt ID: B3GN2_HUMAN
• PDB ID: 6WMM; 6WMN; 6WMO; 7JHK; 7JHL; 7JHM; 7JHN; 7JHO; 8SZ3; 8TIC; 8TJC
• EC Number: 2.4.1.149
• Pfam ID: PF01762
• Sequence:
  MSVGRRRIKLLGILMMANVFIYFIMEVSKSSSQEKNGKGEVIIPKEKFWKISTPPEAYWN
  REQEKLNRQYNPILSMLTNQTGEAGRLSNISHLNYCEPDLRVTSVVTGFNNLPDRFKDFL
  LYLRCRNYSLLIDQPDKCAKKPFLLLAIKSLTPHFARRQAIRESWGQESNAGNQTVVRVF
  LLGQTPPEDNHPDLSDMLKFESEKHQDILMWNYRDTFFNLSLKEVLFLRWVSTSCPDTEF
  VFKGDDDVFVNTHHILNYLNSLSKTKAKDLFIGDVIHNAGPHRDKKLKYYIPEVVYSGLY
  PPYAGGGGFLYSGHLALRLYHITDQVHLYPIDDVYTGMCLQKLGLVPEKHKGFRTFDIEE
  KNKNNICSYVDLMLVHSRKPQEMIDIWSQLQSAHLKC
• Function: Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine. Catalyzes the initiation and elongation of poly-N-acetyllactosamine chains. Shows a marked preference for Gal(beta1-4)Glc(NAc)-based acceptors. Probably constitutes the main polylactosamine synthase.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Glycosaminoglycan biosynthesis - keratan sulfate (hsa00533)
  Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  O-linked glycosylation of mucins (R-HSA-913709)
  Keratan sulfate biosynthesis (R-HSA-2022854)
• BioCyc Pathway: MetaCyc:ENSG00000170340-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial infarction	DIS655KI	Definitive	Biomarker	[1]
Ciliopathy	DIS10G4I	Strong	Biomarker	[2]
Dravet syndrome	DISJF7LY	Strong	Genetic Variation	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[5]
Muscular dystrophy-dystroglycanopathy, type A	DISZTBC4	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Pachyonychia congenita 3	DISZLC6C	Strong	Altered Expression	[7]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[8]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[7]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[7]
Psoriasis	DIS59VMN	Strong	Altered Expression	[9]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[10]
Schizophrenia	DISSRV2N	Strong	Biomarker	[10]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[11]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[12]
Graves disease	DISU4KOQ	moderate	Genetic Variation	[10]
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13	DISZMV14	Moderate	Autosomal recessive	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[19]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[20]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[21]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[21]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[22]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[23]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[24]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[25]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[26]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[31]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[32]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[33]

2 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 affects the methylation of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[27]
Glyphosate	DM0AFY7	Investigative	Glyphosate affects the methylation of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2).	[34]

References

• [1] Association of polymorphisms of platelet membrane integrins alpha IIb(beta)3 (HPA-1b/Pl) and alpha2(beta)1 (alpha807TT) with premature myocardial infarction.J Thromb Haemost. 2005 Jul;3(7):1522-9. doi: 10.1111/j.1538-7836.2005.01432.x.
• [2] Accelerating Gene Discovery by Phenotyping Whole-Genome Sequenced Multi-mutation Strains and Using the Sequence Kernel Association Test (SKAT).PLoS Genet. 2016 Aug 10;12(8):e1006235. doi: 10.1371/journal.pgen.1006235. eCollection 2016 Aug.
• [3] A homozygous mutation of voltage-gated sodium channel (I) gene SCN1B in a patient with Dravet syndrome.Epilepsia. 2012 Dec;53(12):e200-3. doi: 10.1111/epi.12040. Epub 2012 Nov 13.
• [4] B3GNT2, a polylactosamine synthase, regulates glycosylation of EGFR in H7721 human hepatocellular carcinoma cells.Asian Pac J Cancer Prev. 2014;15(24):10875-8. doi: 10.7314/apjcp.2014.15.24.10875.
• [5] Integrative data mining highlights candidate genes for monogenic myopathies.PLoS One. 2014 Oct 29;9(10):e110888. doi: 10.1371/journal.pone.0110888. eCollection 2014.
• [6] 12-month patterns of serum markers of collagen synthesis, transforming growth factor and connective tissue growth factor are similar in new-onset and chronic dilated cardiomyopathy in patients both with and without cardiac fibrosis.Cytokine. 2017 Aug;96:217-227. doi: 10.1016/j.cyto.2017.04.021. Epub 2017 Apr 28.
• [7] Missense mutations in -1,3-N-acetylglucosaminyltransferase 1 (B3GNT1) cause Walker-Warburg syndrome. Hum Mol Genet. 2013 May 1;22(9):1746-54. doi: 10.1093/hmg/ddt021. Epub 2013 Jan 28.
• [8] Association between expression levels of CA 19-9 and N-acetylglucosamine-beta;1,3-galactosyltransferase 5 gene in human pancreatic cancer tissue.Pathobiology. 2004;71(1):26-34. doi: 10.1159/000072959.
• [9] Abnormality of RUNX1 signal transduction in psoriatic CD34+ bone marrow cells.Br J Dermatol. 2011 May;164(5):1043-51. doi: 10.1111/j.1365-2133.2010.10192.x.
• [10] Transcriptome study of differential expression in schizophrenia.Hum Mol Genet. 2013 Dec 15;22(24):5001-14. doi: 10.1093/hmg/ddt350. Epub 2013 Jul 30.
• [11] Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population.Nat Genet. 2012 Mar 25;44(5):511-6. doi: 10.1038/ng.2231.
• [12] A novel member of the glycosyltransferase family, beta 3 Gn-T2, highly downregulated in invasive human bladder transitional cell carcinomas.Mol Carcinog. 2001 Oct;32(2):61-72. doi: 10.1002/mc.1065.
• [13] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [14] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [15] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [16] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [17] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [20] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [21] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [22] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [23] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [24] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [25] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [26] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [27] 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.
• [28] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [29] 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.
• [30] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [31] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [32] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [33] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
• [34] Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women. Environ Health Perspect. 2022 Apr;130(4):47001. doi: 10.1289/EHP10174. Epub 2022 Apr 4.