Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1FHFMK)

• DOT Name: Solute carrier family 52, riboflavin transporter, member 3 (SLC52A3)
• Synonyms: Riboflavin transporter 2; hRFT2
• Gene Name: SLC52A3
• Related Disease:
  Brown-Vialetto-van Laere syndrome 1
  Progressive bulbar palsy
• UniProt ID: S52A3_HUMAN
• Pfam ID: PF06237
• Sequence:
  MAFLMHLLVCVFGMGSWVTINGLWVELPLLVMELPEGWYLPSYLTVVIQLANIGPLLVTL
  LHHFRPSCLSEVPIIFTLLGVGTVTCIIFAFLWNMTSWVLDGHHSIAFLVLTFFLALVDC
  TSSVTFLPFMSRLPTYYLTTFFVGEGLSGLLPALVALAQGSGLTTCVNVTEISDSVPSPV
  PTRETDIAQGVPRALVSALPGMEAPLSHLESRYLPAHFSPLVFFLLLSIMMACCLVAFFV
  LQRQPRCWEASVEDLLNDQVTLHSIRPREENDLGPAGTVDSSQGQGYLEEKAAPCCPAHL
  AFIYTLVAFVNALTNGMLPSVQTYSCLSYGPVAYHLAATLSIVANPLASLVSMFLPNRSL
  LFLGVLSVLGTCFGGYNMAMAVMSPCPLLQGHWGGEVLIVASWVLFSGCLSYVKVMLGVV
  LRDLSRSALLWCGAAVQLGSLLGALLMFPLVNVLRLFSSADFCNLHCPA
• Function: Plasma membrane transporter mediating the uptake by cells of the water soluble vitamin B2/riboflavin that plays a key role in biochemical oxidation-reduction reactions of the carbohydrate, lipid, and amino acid metabolism. Humans are unable to synthesize vitamin B2/riboflavin and must obtain it via intestinal absorption.
• Tissue Specificity: Predominantly expressed in testis. Highly expressed in small intestine and prostate.
• KEGG Pathway: Vitamin digestion and absorption (hsa04977)
• Reactome Pathway: Vitamin B2 (riboflavin) metabolism (R-HSA-196843)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brown-Vialetto-van Laere syndrome 1	DISFGXWR	Definitive	Autosomal recessive	[1]
Progressive bulbar palsy	DIS4SNUB	Moderate	Autosomal recessive	[2]

7 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 Solute carrier family 52, riboflavin transporter, member 3 (SLC52A3).	[3]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Solute carrier family 52, riboflavin transporter, member 3 (SLC52A3).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Solute carrier family 52, riboflavin transporter, member 3 (SLC52A3).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Solute carrier family 52, riboflavin transporter, member 3 (SLC52A3).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Solute carrier family 52, riboflavin transporter, member 3 (SLC52A3).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Solute carrier family 52, riboflavin transporter, member 3 (SLC52A3).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Solute carrier family 52, riboflavin transporter, member 3 (SLC52A3).	[9]

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 Solute carrier family 52, riboflavin transporter, member 3 (SLC52A3).	[6]

References

• [1] 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.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [5] 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.
• [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] 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.
• [8] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.