Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXH6KOQ)

• DOT Name: Beta-1,3-glucosyltransferase (B3GLCT)
• Synonyms: Beta3Glc-T; EC 2.4.1.-; Beta 3-glucosyltransferase; Beta-3-glycosyltransferase-like
• Gene Name: B3GLCT
• Related Disease:
  Disorder of orbital region
  Peters anomaly
  Peters plus syndrome
  Anemia
  Autism spectrum disorder
  Brachydactyly
  Cleft lip/palate
  Hydrocephalus
  Hydrocephalus, nonsyndromic, autosomal recessive 1
  Major depressive disorder
  Neovascular age-related macular degeneration
  Popliteal pterygium syndrome
  Atrial septal defect
• UniProt ID: B3GLT_HUMAN
• EC Number: 2.4.1.-
• Pfam ID: PF02434
• Sequence:
  MRPPACWWLLAPPALLALLTCSLAFGLASEDTKKEVKQSQDLEKSGISRKNDIDLKGIVF
  VIQSQSNSFHAKRAEQLKKSILKQAADLTQELPSVLLLHQLAKQEGAWTILPLLPHFSVT
  YSRNSSWIFFCEEETRIQIPKLLETLRRYDPSKEWFLGKALHDEEATIIHHYAFSENPTV
  FKYPDFAAGWALSIPLVNKLTKRLKSESLKSDFTIDLKHEIALYIWDKGGGPPLTPVPEF
  CTNDVDFYCATTFHSFLPLCRKPVKKKDIFVAVKTCKKFHGDRIPIVKQTWESQASLIEY
  YSDYTENSIPTVDLGIPNTDRGHCGKTFAILERFLNRSQDKTAWLVIVDDDTLISISRLQ
  HLLSCYDSGEPVFLGERYGYGLGTGGYSYITGGGGMVFSREAVRRLLASKCRCYSNDAPD
  DMVLGMCFSGLGIPVTHSPLFHQARPVDYPKDYLSHQVPISFHKHWNIDPVKVYFTWLAP
  SDEDKARQETQKGFREEL
• Function: O-glucosyltransferase that transfers glucose toward fucose with a beta-1,3 linkage. Specifically glucosylates O-linked fucosylglycan on TSP type-1 domains of proteins, thereby contributing to elongation of O-fucosylglycan.
• Tissue Specificity: Widely expressed, with highest levels in testis and uterus.
• KEGG Pathway: Other types of O-glycan biosynthesis (hsa00514)
• Reactome Pathway:
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  Defective B3GALTL causes PpS (R-HSA-5083635)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Disorder of orbital region	DISH0ECJ	Definitive	Biomarker	[1]
Peters anomaly	DISERK0M	Definitive	Genetic Variation	[2]
Peters plus syndrome	DISIUM7O	Definitive	Autosomal recessive	[3]
Anemia	DISTVL0C	Strong	Biomarker	[4]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[5]
Brachydactyly	DIS2533F	Strong	Genetic Variation	[6]
Cleft lip/palate	DIS14IG3	Strong	Genetic Variation	[7]
Hydrocephalus	DISIZUF7	Strong	Genetic Variation	[6]
Hydrocephalus, nonsyndromic, autosomal recessive 1	DISCYZI4	Strong	Genetic Variation	[6]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[8]
Neovascular age-related macular degeneration	DIS5S9R7	Strong	Genetic Variation	[9]
Popliteal pterygium syndrome	DISRS4H8	Strong	Biomarker	[10]
Atrial septal defect	DISJT76B	moderate	Biomarker	[5]

8 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 Beta-1,3-glucosyltransferase (B3GLCT).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Beta-1,3-glucosyltransferase (B3GLCT).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Beta-1,3-glucosyltransferase (B3GLCT).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Beta-1,3-glucosyltransferase (B3GLCT).	[14]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Beta-1,3-glucosyltransferase (B3GLCT).	[15]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Beta-1,3-glucosyltransferase (B3GLCT).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Beta-1,3-glucosyltransferase (B3GLCT).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Beta-1,3-glucosyltransferase (B3GLCT).	[15]

References

• [1] Mutation analysis of B3GALTL in Peters Plus syndrome.Am J Med Genet A. 2008 Oct 15;146A(20):2603-10. doi: 10.1002/ajmg.a.32498.
• [2] Novel B3GALTL mutations in classic Peters plus syndrome and lack of mutations in a large cohort of patients with similar phenotypes.Clin Genet. 2014 Aug;86(2):142-8. doi: 10.1111/cge.12241. Epub 2013 Sep 17.
• [3] Peters Plus syndrome is a new congenital disorder of glycosylation and involves defective Omicron-glycosylation of thrombospondin type 1 repeats. J Biol Chem. 2008 Mar 21;283(12):7354-60. doi: 10.1074/jbc.M710251200. Epub 2008 Jan 16.
• [4] Molecular predictors for anaemia after kidney transplantation.Nephrol Dial Transplant. 2009 Mar;24(3):1015-23. doi: 10.1093/ndt/gfn683. Epub 2008 Dec 18.
• [5] Genetics of anterior segment dysgenesis disorders. Curr Opin Ophthalmol. 2011 Sep;22(5):314-24. doi: 10.1097/ICU.0b013e328349412b.
• [6] ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome.Hum Mol Genet. 2019 Dec 15;28(24):4053-4066. doi: 10.1093/hmg/ddz225.
• [7] Hydrocephalus, agenesis of the corpus callosum, and cleft lip/palate represent frequent associations in fetuses with Peters' plus syndrome and B3GALTL mutations. Fetal PPS phenotypes, expanded by Dandy Walker cyst and encephalocele.Prenat Diagn. 2013 Jan;33(1):75-80. doi: 10.1002/pd.4012. Epub 2012 Nov 13.
• [8] Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways.Nat Commun. 2018 Apr 16;9(1):1470. doi: 10.1038/s41467-018-03819-3.
• [9] A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.Nat Genet. 2016 Feb;48(2):134-43. doi: 10.1038/ng.3448. Epub 2015 Dec 21.
• [10] Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.PLoS One. 2017 Sep 19;12(9):e0184903. doi: 10.1371/journal.pone.0184903. eCollection 2017.
• [11] 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.
• [12] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [13] 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.
• [14] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [17] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.