Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM543US)

• DOT Name: GDP-fucose transporter 1 (SLC35C1)
• Synonyms: Solute carrier family 35 member C1
• Gene Name: SLC35C1
• Related Disease: Leukocyte adhesion deficiency type II
• UniProt ID: FUCT1_HUMAN
• Pfam ID: PF03151
• Sequence:
  MNRAPLKRSRILHMALTGASDPSAEAEANGEKPFLLRALQIALVVSLYWVTSISMVFLNK
  YLLDSPSLRLDTPIFVTFYQCLVTTLLCKGLSALAACCPGAVDFPSLRLDLRVARSVLPL
  SVVFIGMITFNNLCLKYVGVAFYNVGRSLTTVFNVLLSYLLLKQTTSFYALLTCGIIIGG
  FWLGVDQEGAEGTLSWLGTVFGVLASLCVSLNAIYTTKVLPAVDGSIWRLTFYNNVNACI
  LFLPLLLLLGELQALRDFAQLGSAHFWGMMTLGGLFGFAIGYVTGLQIKFTSPLTHNVSG
  TAKACAQTVLAVLYYEETKSFLWWTSNMMVLGGSSAYTWVRGWEMKKTPEEPSPKDSEKS
  AMGV
• Function: Antiporter specific for GDP-l-fucose and depending on the concomitant reverse transport of GMP. Involved in GDP-fucose import from the cytoplasm into the Golgi lumen.
• Reactome Pathway:
  GDP-fucose biosynthesis (R-HSA-6787639)
  Transport of nucleotide sugars (R-HSA-727802)
  Defective SLC35C1 causes congenital disorder of glycosylation 2C (CDG2C) (R-HSA-5619078)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leukocyte adhesion deficiency type II	DISYHBB7	Definitive	Autosomal recessive	[1]

7 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 GDP-fucose transporter 1 (SLC35C1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of GDP-fucose transporter 1 (SLC35C1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GDP-fucose transporter 1 (SLC35C1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of GDP-fucose transporter 1 (SLC35C1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of GDP-fucose transporter 1 (SLC35C1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of GDP-fucose transporter 1 (SLC35C1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of GDP-fucose transporter 1 (SLC35C1).	[10]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the methylation of GDP-fucose transporter 1 (SLC35C1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of GDP-fucose transporter 1 (SLC35C1).	[8]

References

• [1] The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. Nat Genet. 2001 May;28(1):69-72. doi: 10.1038/ng0501-69.
• [2] 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.
• [3] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort. Environ Pollut. 2021 Dec 1;290:118024. doi: 10.1016/j.envpol.2021.118024. Epub 2021 Aug 21.
• [8] 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.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.