Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ63YNA)

• DOT Name: Monocarboxylate transporter 12 (SLC16A12)
• Synonyms: MCT 12; Creatine transporter 2; CRT2; Solute carrier family 16 member 12
• Gene Name: SLC16A12
• Related Disease: Juvenile cataract-microcornea-renal glucosuria syndrome
• UniProt ID: MOT12_HUMAN
• Pfam ID: PF07690
• Sequence:
  MPSGSHWTANSSKIITWLLEQPGKEEKRKTMAKVNRARSTSPPDGGWGWMIVAGCFLVTI
  CTRAVTRCISIFFVEFQTYFTQDYAQTAWIHSIVDCVTMLCAPLGSVVSNHLSCQVGIML
  GGLLASTGLILSSFATSLKHLYLTLGVLTGLGFALCYSPAIAMVGKYFSRRKALAYGIAM
  SGSGIGTFILAPVVQLLIEQFSWRGALLILGGFVLNLCVCGALMRPITLKEDHTTPEQNH
  VCRTQKEDIKRVSPYSSLTKEWAQTCLCCCLQQEYSFLLMSDFVVLAVSVLFMAYGCSPL
  FVYLVPYALSVGVSHQQAAFLMSILGVIDIIGNITFGWLTDRRCLKNYQYVCYLFAVGMD
  GLCYLCLPMLQSLPLLVPFSCTFGYFDGAYVTLIPVVTTEIVGTTSLSSALGVVYFLHAV
  PYLVSPPIAGRLVDTTGSYTAAFLLCGFSMIFSSVLLGFARLIKRMRKTQLQFIAKESDP
  KLQLWTNGSVAYSVARELDQKHGEPVATAVPGYSLT
• Function: Functions as a transporter for creatine and as well for its precursor guanidinoacetate. Transport of creatine and GAA is independent of resting membrane potential and extracellular Na(+), Cl(-), or pH. Contributes to the process of creatine biosynthesis and distribution.
• Tissue Specificity: Most highly expressed in kidney, followed by retina, lung, heart and testis. Very weakly expressed in brain and liver. Also detected in lens.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Juvenile cataract-microcornea-renal glucosuria syndrome	DISYZY5W	Strong	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Monocarboxylate transporter 12 (SLC16A12).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Monocarboxylate transporter 12 (SLC16A12).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Monocarboxylate transporter 12 (SLC16A12).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Monocarboxylate transporter 12 (SLC16A12).	[5]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Monocarboxylate transporter 12 (SLC16A12).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Monocarboxylate transporter 12 (SLC16A12).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Monocarboxylate transporter 12 (SLC16A12).	[9]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Monocarboxylate transporter 12 (SLC16A12).	[10]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Monocarboxylate transporter 12 (SLC16A12).	[11]

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 Monocarboxylate transporter 12 (SLC16A12).	[7]

References

• [1] Mutation of solute carrier SLC16A12 associates with a syndrome combining juvenile cataract with microcornea and renal glucosuria. Am J Hum Genet. 2008 Mar;82(3):772-9. doi: 10.1016/j.ajhg.2007.12.013. Epub 2008 Feb 14.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
• [7] 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.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [9] 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.
• [10] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [11] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.