Details of Drug Off-Target (DOT)

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

• DOT Name: UDP-galactose translocator (SLC35A2)
• Synonyms: Solute carrier family 35 member A2; UDP-galactose transporter; UDP-Gal-Tr; UGT
• Gene Name: SLC35A2
• Related Disease:
  SLC35A2-congenital disorder of glycosylation
  X-linked complex neurodevelopmental disorder
• UniProt ID: S35A2_HUMAN
• Pfam ID: PF04142
• Sequence:
  MAAVGAGGSTAAPGPGAVSAGALEPGTASAAHRRLKYISLAVLVVQNASLILSIRYARTL
  PGDRFFATTAVVMAEVLKGLTCLLLLFAQKRGNVKHLVLFLHEAVLVQYVDTLKLAVPSL
  IYTLQNNLQYVAISNLPAATFQVTYQLKILTTALFSVLMLNRSLSRLQWASLLLLFTGVA
  IVQAQQAGGGGPRPLDQNPGAGLAAVVASCLSSGFAGVYFEKILKGSSGSVWLRNLQLGL
  FGTALGLVGLWWAEGTAVATRGFFFGYTPAVWGVVLNQAFGGLLVAVVVKYADNILKGFA
  TSLSIVLSTVASIRLFGFHVDPLFALGAGLVIGAVYLYSLPRGAAKAIASASASASGPCV
  HQQPPGQPPPPQLSSHRGDLITEPFLPKLLTKVKGS
• Function: Transports uridine diphosphate galactose (UDP-galactose) from the cytosol into the Golgi apparatus, functioning as an antiporter that exchanges UDP-galactose for UMP. It is also able to exchange UDP-galactose for AMP and CMP, and to transport UDP-N-acetylgalactosamine (UDP-GalNAc) and other nucleotide sugars. As a provider of UDP-galactose to galactosyltransferases present in the Golgi apparatus, it is necessary for globotriaosylceramide/globoside (Gb3Cer) synthesis from lactosylceramide.
• Reactome Pathway:
  Transport of nucleotide sugars (R-HSA-727802)
  Defective SLC35A2 causes congenital disorder of glycosylation 2M (CDG2M) (R-HSA-5619072)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
SLC35A2-congenital disorder of glycosylation	DIST8VOO	Definitive	X-linked	[1]
X-linked complex neurodevelopmental disorder	DISI3QE9	Definitive	X-linked	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of UDP-galactose translocator (SLC35A2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of UDP-galactose translocator (SLC35A2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of UDP-galactose translocator (SLC35A2).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of UDP-galactose translocator (SLC35A2).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of UDP-galactose translocator (SLC35A2).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of UDP-galactose translocator (SLC35A2).	[8]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of UDP-galactose translocator (SLC35A2).	[10]

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 decreases the methylation of UDP-galactose translocator (SLC35A2).	[9]

References

• [1] De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early-onset epileptic encephalopathy. Hum Mutat. 2013 Dec;34(12):1708-14. doi: 10.1002/humu.22446. Epub 2013 Oct 15.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] 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.
• [10] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.