Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG5WHRW)

• DOT Name: Beta-1,4-galactosyltransferase 7 (B4GALT7)
• Synonyms: Beta-1,4-GalTase 7; Beta4Gal-T7; b4Gal-T7; EC 2.4.1.-; Proteoglycan UDP-galactose:beta-xylose beta1,4-galactosyltransferase I; UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 7; UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 7; UDP-galactose:beta-xylose beta-1,4-galactosyltransferase; XGPT; XGalT-1; Xylosylprotein 4-beta-galactosyltransferase; EC 2.4.1.133; Xylosylprotein beta-1,4-galactosyltransferase
• Gene Name: B4GALT7
• Related Disease:
  Ehlers-Danlos syndrome, spondylodysplastic type, 1
  Ehlers-Danlos syndrome, spondylodysplastic type
• UniProt ID: B4GT7_HUMAN
• PDB ID: 4IRP; 4IRQ
• EC Number: 2.4.1.-; 2.4.1.133
• Pfam ID: PF02709 ; PF13733
• Sequence:
  MFPSRRKAAQLPWEDGRSGLLSGGLPRKCSVFHLFVACLSLGFFSLLWLQLSCSGDVARA
  VRGQGQETSGPPRACPPEPPPEHWEEDASWGPHRLAVLVPFRERFEELLVFVPHMRRFLS
  RKKIRHHIYVLNQVDHFRFNRAALINVGFLESSNSTDYIAMHDVDLLPLNEELDYGFPEA
  GPFHVASPELHPLYHYKTYVGGILLLSKQHYRLCNGMSNRFWGWGREDDEFYRRIKGAGL
  QLFRPSGITTGYKTFRHLHDPAWRKRDQKRIAAQKQEQFKVDREGGLNTVKYHVASRTAL
  SVGGAPCTVLNIMLDCDKTATPWCTFS
• Function: Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts.
• Tissue Specificity: High expression in heart, pancreas and liver, medium in placenta and kidney, low in brain, skeletal muscle and lung.
• KEGG Pathway:
  Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate (hsa00532)
  Glycosaminoglycan biosynthesis - heparan sulfate / heparin (hsa00534)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Defective B4GALT7 causes EDS, progeroid type (R-HSA-3560783)
  A tetrasaccharide linker sequence is required for GAG synthesis (R-HSA-1971475)
• BioCyc Pathway: MetaCyc:HS00459-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ehlers-Danlos syndrome, spondylodysplastic type, 1	DISJ607K	Definitive	Autosomal recessive	[1]
Ehlers-Danlos syndrome, spondylodysplastic type	DISFYHM7	Supportive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Beta-1,4-galactosyltransferase 7 (B4GALT7).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Beta-1,4-galactosyltransferase 7 (B4GALT7).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Beta-1,4-galactosyltransferase 7 (B4GALT7).	[4]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Beta-1,4-galactosyltransferase 7 (B4GALT7).	[5]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Beta-1,4-galactosyltransferase 7 (B4GALT7).	[7]

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 Beta-1,4-galactosyltransferase 7 (B4GALT7).	[6]

References

• [1] A novel missense mutation in the galactosyltransferase-I (B4GALT7) gene in a family exhibiting facioskeletal anomalies and Ehlers-Danlos syndrome resembling the progeroid type. Am J Med Genet A. 2004 Jul 1;128A(1):39-45. doi: 10.1002/ajmg.a.30005.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] 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.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [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.
• [7] Ochratoxin a lowers mRNA levels of genes encoding for key proteins of liver cell metabolism. Cancer Genomics Proteomics. 2008 Nov-Dec;5(6):319-32.