Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1T1FMB)

• DOT Name: Solute carrier family 25 member 36 (SLC25A36)
• Gene Name: SLC25A36
• Related Disease: Hyperinsulinemic hypoglycemia, familial, 8
• UniProt ID: S2536_HUMAN
• Pfam ID: PF00153
• Sequence:
  MSQRDTLVHLFAGGCGGTVGAILTCPLEVVKTRLQSSSVTLYISEVQLNTMAGASVNRVV
  SPGPLHCLKVILEKEGPRSLFRGLGPNLVGVAPSRAIYFAAYSNCKEKLNDVFDPDSTQV
  HMISAAMAGFTAITATNPIWLIKTRLQLDARNRGERRMGAFECVRKVYQTDGLKGFYRGM
  SASYAGISETVIHFVIYESIKQKLLEYKTASTMENDEESVKEASDFVGMMLAAATSKTCA
  TTIAYPHEVVRTRLREEGTKYRSFFQTLSLLVQEEGYGSLYRGLTTHLVRQIPNTAIMMA
  TYELVVYLLNG
• Function: Mitochondrial transporter that imports/exports pyrimidine nucleotides into and from mitochondria. Selectively transports cytosine, guanosine, inosine and uridine (deoxy)nucleoside mono-, di-, and triphosphates by antiport mechanism. Catalyzes uniport at much lower rate. May import (deoxy)nucleoside triphosphates in exchange for intramitochondrial (deoxy)nucleoside mono- and diphosphates, thus providing precursors necessary for de novo synthesis of mitochondrial DNA and RNA while exporting products of their catabolism. Participates in mitochondrial genome maintenance, regulation of mitochondrial membrane potential and mitochondrial respiration.
• Tissue Specificity: Widely expressed at moderate level. Expressed most strongly in pancreas .

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperinsulinemic hypoglycemia, familial, 8	DISQ5SYQ	Limited	Autosomal recessive	[1]

16 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 Solute carrier family 25 member 36 (SLC25A36).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Solute carrier family 25 member 36 (SLC25A36).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Solute carrier family 25 member 36 (SLC25A36).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Solute carrier family 25 member 36 (SLC25A36).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Solute carrier family 25 member 36 (SLC25A36).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Solute carrier family 25 member 36 (SLC25A36).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Solute carrier family 25 member 36 (SLC25A36).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Solute carrier family 25 member 36 (SLC25A36).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Solute carrier family 25 member 36 (SLC25A36).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Solute carrier family 25 member 36 (SLC25A36).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Solute carrier family 25 member 36 (SLC25A36).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Solute carrier family 25 member 36 (SLC25A36).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Solute carrier family 25 member 36 (SLC25A36).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Solute carrier family 25 member 36 (SLC25A36).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Solute carrier family 25 member 36 (SLC25A36).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Solute carrier family 25 member 36 (SLC25A36).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Solute carrier family 25 member 36 (SLC25A36).	[6]

References

• [1] 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.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] 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.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] 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.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [14] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [15] 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.
• [16] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.