Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0444 Transporter Info
Gene Name SLC6A12
Transporter Name Na(+)/Cl(-) betaine/GABA transporter
Gene ID
6539
UniProt ID
P48065
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Approved Drug

  Arsenic Trioxide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Arsenic Trioxide inhibits the expression of SLC6A12 [1]

  Copper Sulfate

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Copper Sulfate inhibits the expression of SLC6A12 [2]

  Estradiol

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Estradiol inhibits the expression of SLC6A12 [3]

  Zidovudine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Zidovudine increases the expression of SLC6A12 [4]

  Rifampin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Rifampin increases the expression of SLC6A12 [5]

  Cisplatin

            3 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Cisplatin inhibits the expression of SLC6A12 [6]

  Leflunomide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Leflunomide inhibits the expression of SLC6A12 [7]

  Valproic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Valproic Acid increases the expression of SLC6A12 [8]

  Cyclosporine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Cyclosporine inhibits the expression of SLC6A12 [9]

  Aspirin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 SLC6A12 polymorphism affects the susceptibility to Aspirin [28]

Regulation Mechanism

 Transcription Factor Info

Drug in Phase 3 Trial

  Triclosan

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Triclosan increases the expression of SLC6A12 [16]

Drug in Phase 2 Trial

  Genistein

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Genistein increases the expression of SLC6A12 [13]

Drug in Phase 1 Trial

  Quercetin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Quercetin increases the expression of SLC6A12 [11]

Investigative Drug

  NNC052090

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 NNC052090 inhibits the activity of SLC6A12 [20]

  LU32-176B

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 LU32-176B inhibits the activity of SLC6A12 [21]

  (R/S) EF-1500

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 (R/S) EF-1500 inhibits the activity of SLC6A12 [22]

  (R)-EF-1520

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 (R)-EF-1520 inhibits the activity of SLC6A12 [22]

  (S)-EF-1520

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 (S)-EF-1520 inhibits the activity of SLC6A12 [22]

Natural Product

  Tobacco Smoke Pollution

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Tobacco Smoke Pollution increases the expression of SLC6A12 [18]

Traditional Medicine

  Jinfukang

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Jinfukang inhibits the expression of SLC6A12 [6]

Mycotoxins

  Aflatoxin B1

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Aflatoxin B1 increases the expression of SLC6A12 [12]

  DT Modulation2

 Aflatoxin B1 affects the expression of SLC6A12 protein [3]

Regulation Mechanism

 Transcription Factor Info

  aflatoxin B2

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 aflatoxin B2 results in decreased methylation of SLC6A12 exon [25]

Regulation Mechanism

 Transcription Factor Info

Carcinogen

  Benzo(a)pyrene

            3 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Benzo(a)pyrene inhibits the expression of SLC6A12 [19]

  Arsenic

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 sodium arsenate results in increased abundance of Arsenic which results in decreased expression of SLC6A12 mRNA [27]

Regulation Mechanism

 Transcription Factor Info

Pesticide/Insecticide

  Dicrotophos

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Dicrotophos inhibits the expression of SLC6A12 [15]

Health and Environmental Toxicant

  tris(1,3-dichloro-2-propyl)phosphate

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 tris(1,3-dichloro-2-propyl)phosphate inhibits the expression of SLC6A12 [14]

  Diethylhexyl Phthalate

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Diethylhexyl Phthalate inhibits the expression of SLC6A12 [17]

Chemical Compound

  DT Modulation1

 Estradiol results in increased expression of SLC6A12 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Cisplatin co-treated with jinfukang results in decreased expression of SLC6A12 mRNA [6]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 SLC6A12 protein affects the susceptibility to Cisplatin [31]

Regulation Mechanism

 Transcription Factor Info

  Sodium Chloride

            3 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sodium Chloride increases the expression of SLC6A12 [10]

  DT Modulation2

 myxothiazol inhibits the reaction Sodium Chloride results in increased expression of SLC6A12 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Rotenone inhibits the reaction Sodium Chloride results in increased expression of SLC6A12 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Diethylhexyl Phthalate results in increased expression of SLC6A12 mRNA [33]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Benzo(a)pyrene affects the methylation of SLC6A12 promoter [29]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene results in decreased methylation of SLC6A12 5' UTR [29]

Regulation Mechanism

 Transcription Factor Info

  2-palmitoylglycerol

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 2-palmitoylglycerol results in increased expression of SLC6A12 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

  abrine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 abrine results in increased expression of SLC6A12 mRNA [24]

Regulation Mechanism

 Transcription Factor Info

  aristolochic acid I

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 aristolochic acid I results in increased expression of SLC6A12 mRNA [26]

Regulation Mechanism

 Transcription Factor Info

  benzo(e)pyrene

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 benzo(e)pyrene results in decreased methylation of SLC6A12 exon [25]

Regulation Mechanism

 Transcription Factor Info

  bisphenol A

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 bisphenol A co-treated with Fulvestrant results in decreased methylation of SLC6A12 gene [30]

Regulation Mechanism

 Transcription Factor Info

  Dichlorodiphenyl Dichloroethylene

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Dichlorodiphenyl Dichloroethylene results in decreased expression of SLC6A12 mRNA [32]

Regulation Mechanism

 Transcription Factor Info

  dicrotophos

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 dicrotophos results in decreased expression of SLC6A12 mRNA [15]

Regulation Mechanism

 Transcription Factor Info

  Esketamine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Esketamine results in increased expression of SLC6A12 mRNA [34]

Regulation Mechanism

 Transcription Factor Info

  Fulvestrant

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 bisphenol A co-treated with Fulvestrant results in decreased methylation of SLC6A12 gene [30]

Regulation Mechanism

 Transcription Factor Info

  Methapyrilene

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Methapyrilene results in decreased methylation of SLC6A12 exon [25]

Regulation Mechanism

 Transcription Factor Info

  myxothiazol

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 myxothiazol inhibits the reaction Sodium Chloride results in increased expression of SLC6A12 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  Palmitic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Palmitic Acid results in increased expression of SLC6A12 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

  perfluorooctane sulfonic acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 perfluorooctane sulfonic acid results in decreased expression of SLC6A12 mRNA [35]

Regulation Mechanism

 Transcription Factor Info

  Rotenone

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Rotenone inhibits the reaction Sodium Chloride results in increased expression of SLC6A12 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  S-(1,2-dichlorovinyl)cysteine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 S-(1,2-dichlorovinyl)cysteine affects the susceptibility to Lipopolysaccharides which results in increased expression of SLC6A12 mRNA [36]

Regulation Mechanism

 Transcription Factor Info

  Silicon Dioxide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Silicon Dioxide analog results in decreased expression of SLC6A12 mRNA [37]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenate

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 sodium arsenate results in increased abundance of Arsenic which results in decreased expression of SLC6A12 mRNA [27]

Regulation Mechanism

 Transcription Factor Info

  theaflavin-3,3'-digallate

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 theaflavin-3,3'-digallate affects the expression of SLC6A12 mRNA [38]

Regulation Mechanism

 Transcription Factor Info

  triphenyl phosphate

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 triphenyl phosphate affects the expression of SLC6A12 mRNA [39]

Regulation Mechanism

 Transcription Factor Info
References
1 Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
2 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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 Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23.
5 Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
6 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
8 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.
9 Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel. Toxicol Appl Pharmacol. 2014 Sep 1;279(2):163-72.
10 Mitochondrial reactive oxygen species contribute to high NaCl-induced activation of the transcription factor TonEBP/OREBP. Am J Physiol Renal Physiol. 2006 May;290(5):F1169-76.
11 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
12 Aflatoxins upregulate CYP3A4 mRNA expression in a process that involves the PXR transcription factor. Toxicol Lett. 2011 Aug 28;205(2):146-53.
13 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.
14 Defensive and adverse energy-related molecular responses precede tris (1, 3-dichloro-2-propyl) phosphate cytotoxicity. J Appl Toxicol. 2016 May;36(5):649-58.
15 Molecular mechanisms of discrotophos-induced toxicity in HepG2 cells: The role of CSA in oxidative stress. Food Chem Toxicol. 2017 May;103:253-260.
16 Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
17 Di-(2-ethylhexyl)-phthalate induces apoptosis via the PPAR Gamma/PTEN/AKT pathway in differentiated human embryonic stem cells. Food Chem Toxicol. 2019 Sep;131:110552.
18 Integration of transcriptome analysis with pathophysiological endpoints to evaluate cigarette smoke toxicity in an in vitro human airway tissue model. Arch Toxicol. 2021 May;95(5):1739-1761.
19 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297.
20 1-(3-(9H-carbazol-9-yl)-1-propyl)-4-(2-methoxyphenyl)-4-piperidinol, a novel subtype selective inhibitor of the mouse type II GABA-transporter. Br J Pharmacol. 1997 Mar;120(6):983-5.
21 First demonstration of a functional role for central nervous system betaine/{gamma}-aminobutyric acid transporter (mGAT2) based on synergistic anticonvulsant action among inhibitors of mGAT1 and mGAT2. J Pharmacol Exp Ther. 2005 Feb;312(2):866-74.
22 Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 932).
23 Direct effect of 2-palmitoyl glycerol on promotion of gamma aminobutyric acid synthesis in normal human fetal-derived astrocytes. FEBS Open Bio. 2023;13(7):1320-1332.
24 Integration of transcriptomics, proteomics and metabolomics data to reveal the biological mechanisms of abrin injury in human lung epithelial cells. Toxicol Lett. 2019;312:1-10.
25 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018;121:214-223.
26 Integration of transcriptomic, proteomic and metabolomic data to reveal the biological mechanisms of AAI injury in renal epithelial cells. Toxicol In Vitro. 2021;70:105054.
27 Effects of Inorganic Arsenic on Human Prostate Stem-Progenitor Cell Transformation, Autophagic Flux Blockade, and NRF2 Pathway Activation. Environ Health Perspect. 2020;128(6):67008.
28 Association of SLC6A12 variants with aspirin-intolerant asthma in a Korean population. Ann Hum Genet. 2010 Jul;74(4):326-34.
29 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
30 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
31 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006;118(7):1699-712.
32 High-Throughput Transcriptomics of Nontumorigenic Breast Cells Exposed to Environmentally Relevant Chemicals. Environ Health Perspect. 2024;132(4):47002.
33 Long-term di (2-ethylhexyl)-phthalate exposure promotes proliferation and survival of HepG2 cells via activation of NFB. Toxicol In Vitro. 2017;42:86-92.
34 Esketamine induces apoptosis of nasopharyngeal carcinoma cells through the PERK/CHOP pathway. Toxicol Appl Pharmacol. 2024;483:116800.
35 Determination of in vitro hepatotoxic potencies of a series of perfluoroalkyl substances (PFASs) based on gene expression changes in HepaRG liver cells. Arch Toxicol. 2023;97(4):1113-1131.
36 The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine inhibits lipopolysaccharide-induced inflammation transcriptomic pathways and cytokine secretion in a macrophage cell model. Toxicol In Vitro. 2022;84:105429.
37 High-throughput, quantitative assessment of the effects of low-dose silica nanoparticles on lung cells: grasping complex toxicity with a great depth of field. BMC Genomics. 2015;16(1):315.
38 Theaflavin 3, 3'-Digallate Delays Ovarian Aging by Improving Oocyte Quality and Regulating Granulosa Cell Function. Oxid Med Cell Longev. 2021;2021:7064179.
39 Association between Organophosphate Ester Exposure and Insulin Resistance with Glycometabolic Disorders among Older Chinese Adults 60-69 Years of Age: Evidence from the China BAPE Study. Environ Health Perspect. 2023;131(4):47009.

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