Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIDXQ9F)

• DOT Name: Tricarboxylate transport protein, mitochondrial (SLC25A1)
• Synonyms: Citrate transport protein; CTP; Mitochondrial citrate carrier; CIC; Solute carrier family 25 member 1; Tricarboxylate carrier protein
• Gene Name: SLC25A1
• Related Disease:
  Mitochondrial disease
  D,L-2-hydroxyglutaric aciduria
  Myasthenic syndrome, congenital, 23, presynaptic
  Obsolete presynaptic congenital myasthenic syndrome
• UniProt ID: TXTP_HUMAN
• Pfam ID: PF00153
• Sequence:
  MPAPRAPRALAAAAPASGKAKLTHPGKAILAGGLAGGIEICITFPTEYVKTQLQLDERSH
  PPRYRGIGDCVRQTVRSHGVLGLYRGLSSLLYGSIPKAAVRFGMFEFLSNHMRDAQGRLD
  STRGLLCGLGAGVAEAVVVVCPMETIKVKFIHDQTSPNPKYRGFFHGVREIVREQGLKGT
  YQGLTATVLKQGSNQAIRFFVMTSLRNWYRGDNPNKPMNPLITGVFGAIAGAASVFGNTP
  LDVIKTRMQGLEAHKYRNTWDCGLQILKKEGLKAFYKGTVPRLGRVCLDVAIVFVIYDEV
  VKLLNKVWKTD
• Function: Mitochondrial electroneutral antiporter that exports citrate from the mitochondria into the cytosol in exchange for malate. Also able to mediate the exchange of citrate for isocitrate, phosphoenolpyruvate, cis-aconitate and to a lesser extend cis-aconitate, maleate and succinate. In the cytoplasm citrate is important in the regulation of glycolysis through a feedback mechanism and in the production of acetyl-CoA which is needed for the synthesis of fatty acids, sterols, prostaglandins, dolichol and coenzyme Q (CoQ). Required for proper neuromuscular junction formation (Probable).
• Reactome Pathway:
  Fatty acyl-CoA biosynthesis (R-HSA-75105)
  Gluconeogenesis (R-HSA-70263)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[1]
D,L-2-hydroxyglutaric aciduria	DISYBXFL	Strong	Autosomal recessive	[2]
Myasthenic syndrome, congenital, 23, presynaptic	DIS2MO09	Strong	Autosomal recessive	[3]
Obsolete presynaptic congenital myasthenic syndrome	DISCATK3	Supportive	Autosomal dominant	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[15]
Selenium	DM25CGV	Approved	Selenium increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[16]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[17]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[18]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[19]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[20]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[16]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[6]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Tricarboxylate transport protein, mitochondrial (SLC25A1).	[24]

References

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• [2] Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. Am J Hum Genet. 2013 Apr 4;92(4):627-31. doi: 10.1016/j.ajhg.2013.03.009.
• [3] 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.
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• [15] Epigenetic mechanisms and Sp1 regulate mitochondrial citrate carrier gene expression. Biochem Biophys Res Commun. 2008 Nov 7;376(1):15-20. doi: 10.1016/j.bbrc.2008.08.015. Epub 2008 Aug 13.
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• [18] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
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• [24] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.