Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPP3NWG)

• DOT Name: Solute carrier family 25 member 32 (SLC25A32)
• Synonyms: Mitochondrial FAD transporter
• Gene Name: SLC25A32
• Related Disease: Exercise intolerance, riboflavin-responsive
• UniProt ID: S2532_HUMAN
• Pfam ID: PF00153
• Sequence:
  MTGQGQSASGSSAWSTVFRHVRYENLIAGVSGGVLSNLALHPLDLVKIRFAVSDGLELRP
  KYNGILHCLTTIWKLDGLRGLYQGVTPNIWGAGLSWGLYFFFYNAIKSYKTEGRAERLEA
  TEYLVSAAEAGAMTLCITNPLWVTKTRLMLQYDAVVNSPHRQYKGMFDTLVKIYKYEGVR
  GLYKGFVPGLFGTSHGALQFMAYELLKLKYNQHINRLPEAQLSTVEYISVAALSKIFAVA
  ATYPYQVVRARLQDQHMFYSGVIDVITKTWRKEGVGGFYKGIAPNLIRVTPACCITFVVY
  ENVSHFLLDLREKRK
• Function: Facilitates flavin adenine dinucleotide (FAD) translocation across the mitochondrial inner membrane into the mitochondrial matrix where it acts as a redox cofactor to assist flavoenzyme activities in fundamental metabolic processes including fatty acid beta-oxidation, amino acid and choline metabolism as well as mitochondrial electron transportation. In particular, provides FAD to DLD dehydrogenase of the glycine cleavage system, part of mitochondrial one-carbon metabolic pathway involved in neural tube closure in early embryogenesis.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: Metabolism of folate and pterines (R-HSA-196757)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Exercise intolerance, riboflavin-responsive	DISOO5SN	Limited	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Solute carrier family 25 member 32 (SLC25A32).	[2]

8 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 Solute carrier family 25 member 32 (SLC25A32).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Solute carrier family 25 member 32 (SLC25A32).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Solute carrier family 25 member 32 (SLC25A32).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Solute carrier family 25 member 32 (SLC25A32).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Solute carrier family 25 member 32 (SLC25A32).	[7]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Solute carrier family 25 member 32 (SLC25A32).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Solute carrier family 25 member 32 (SLC25A32).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Solute carrier family 25 member 32 (SLC25A32).	[10]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [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] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [6] 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.
• [7] 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.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] 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.