Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0085 Transporter Info
Gene Name SLC12A4
Transporter Name Electroneutral potassium-chloride cotransporter 1
Gene ID
6560
UniProt ID
Q9UP95
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Coumestrol co-treated with 2,3-bis(3'-hydroxybenzyl)butyrolactone results in increased expression of SLC12A4 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Coumestrol co-treated with Resveratrol results in increased expression of SLC12A4 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Benzo(a)pyrene affects the methylation of SLC12A4 exon [23]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene results in increased methylation of SLC12A4 promoter [23]

Regulation Mechanism

 Transcription Factor Info

  1-Methyl-4-phenylpyridinium

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

  DT Modulation1

 1-Methyl-4-phenylpyridinium results in increased expression of SLC12A4 mRNA [14]

Regulation Mechanism

 Transcription Factor Info

  2,3-bis(3'-hydroxybenzyl)butyrolactone

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

  DT Modulation1

 Coumestrol co-treated with 2,3-bis(3'-hydroxybenzyl)butyrolactone results in increased expression of SLC12A4 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine

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

  DT Modulation1

 6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine results in increased expression of SLC12A4 mRNA [20]

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 SLC12A4 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  bisphenol B

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

  DT Modulation1

 bisphenol B results in increased expression of SLC12A4 protein [19]

Regulation Mechanism

 Transcription Factor Info

  bisphenol F

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

  DT Modulation1

 bisphenol F results in increased expression of SLC12A4 protein [19]

Regulation Mechanism

 Transcription Factor Info

  di-n-butylphosphoric acid

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

  DT Modulation1

 di-n-butylphosphoric acid affects the expression of SLC12A4 mRNA [25]

Regulation Mechanism

 Transcription Factor Info

  FR900359

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

  DT Modulation1

 FR900359 affects the phosphorylation of SLC12A4 protein [26]

Regulation Mechanism

 Transcription Factor Info

  K 7174

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

  DT Modulation1

 K 7174 results in increased expression of SLC12A4 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  Manganese

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

  DT Modulation1

 sodium arsenite results in increased abundance of Arsenic co-treated with manganese chloride results in increased abundance of Manganese results in decreased expression of SLC12A4 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

  manganese chloride

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

  DT Modulation1

 sodium arsenite results in increased abundance of Arsenic co-treated with manganese chloride results in increased abundance of Manganese results in decreased expression of SLC12A4 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

  Ozone

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

  DT Modulation1

 Air Pollutants results in increased abundance of Ozone which affects the expression of SLC12A4 mRNA [27]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenite

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

  DT Modulation1

 sodium arsenite results in increased abundance of Arsenic co-treated with manganese chloride results in increased abundance of Manganese results in decreased expression of SLC12A4 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 sodium arsenite results in increased abundance of Arsenic which results in decreased expression of SLC12A4 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 sodium arsenite results in increased expression of SLC12A4 mRNA [28]

Regulation Mechanism

 Transcription Factor Info

  Thiram

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

  DT Modulation1

 Thiram results in increased expression of SLC12A4 mRNA [28]

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 SLC12A4 mRNA [25]

Regulation Mechanism

 Transcription Factor Info

  Valproic Acid

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

  DT Modulation1

 Valproic Acid results in increased methylation of SLC12A4 gene [29]

Regulation Mechanism

 Transcription Factor Info

  Vanadates

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

  DT Modulation1

 Vanadates results in increased expression of SLC12A4 mRNA [30]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Decitabine

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

  DT Modulation1

 Decitabine increases the expression of SLC12A4 [1]

  Estradiol

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

  DT Modulation1

 Estradiol increases the expression of SLC12A4 [2]

  Tretinoin

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

  DT Modulation1

 Tretinoin increases the expression of SLC12A4 [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 SLC12A4 [4]

  Leflunomide

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

  DT Modulation1

 Leflunomide increases the expression of SLC12A4 [5]

  Doxorubicin

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

  DT Modulation1

 Doxorubicin increases the expression of SLC12A4 [6]

  Dactinomycin

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

  DT Modulation1

 Dactinomycin induces the activity of SLC12A4 [8]

Drug Marketed but not Approved by US FDA

  Rotenone

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

  DT Modulation1

 Rotenone increases the expression of SLC12A4 [7]

Drug in Phase 3 Trial

  Resveratrol

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

  DT Modulation1

 Resveratrol increases the expression of SLC12A4 [15]

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 inhibits the expression of SLC12A4 [9]

  Bisphenol B

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

  DT Modulation1

 Bisphenol B increases the expression of SLC12A4 [19]

Drug in Phase 1 Trial

  Quercetin

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

  DT Modulation1

 Quercetin increases the expression of SLC12A4 [12]

Investigative Drug

  Coumestrol

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

  DT Modulation1

 Coumestrol increases the expression of SLC12A4 [2]

Patented Pharmaceutical Agent

  K-7174

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

  DT Modulation1

 K-7174 increases the expression of SLC12A4 [13]

Natural Product

  Coal Ash

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

  DT Modulation1

 Coal Ash increases the expression of SLC12A4 [11]

  DT Modulation1

 Quercetin results in increased phosphorylation of SLC12A4 protein [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Coumestrol co-treated with Resveratrol results in increased expression of SLC12A4 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  Caffeine

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

  DT Modulation1

 Caffeine results in decreased phosphorylation of SLC12A4 protein [24]

Regulation Mechanism

 Transcription Factor Info

Environmental toxicant

  Zinc

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

  DT Modulation1

 Zinc increases the expression of SLC12A4 [10]

  Bisphenol F

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

  DT Modulation1

 Bisphenol F increases the expression of SLC12A4 [19]

Acute Toxic Substance

  Acrylamide

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

  DT Modulation1

 Acrylamide inhibits the expression of SLC12A4 [18]

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 increases the expression of SLC12A4 [17]

  Arsenic

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

  DT Modulation1

 sodium arsenite results in increased abundance of Arsenic co-treated with manganese chloride results in increased abundance of Manganese results in decreased expression of SLC12A4 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 sodium arsenite results in increased abundance of Arsenic which results in decreased expression of SLC12A4 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

Health and Environmental Toxicant

  1-methyl-4-phenylpyridinium

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

  DT Modulation1

 1-methyl-4-phenylpyridinium increases the expression of SLC12A4 [14]

  Lead

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

  DT Modulation1

 Lead affects the expression of SLC12A4 [16]
References
1 Gene induction and apoptosis in human hepatocellular carci-noma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine. Chin Med J (Engl). 2007 Sep 20;120(18):1626-31.
2 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
3 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
4 Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23.
5 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
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 Toxicity, recovery, and resilience in a 3D dopaminergic neuronal in vitro model exposed to rotenone. Arch Toxicol. 2018 Aug;92(8):2587-2606.
8 Nitric oxide signaling pathway regulates potassium chloride cotransporter-1 mRNA expression in vascular smooth muscle cells. J Biol Chem. 2001 Nov 30;276(48):44534-40.
9 Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
10 Zinc deficiency alters DNA damage response genes in normal human prostate epithelial cells. J Nutr. 2008 Apr;138(4):667-73.
11 Endothelial effects of emission source particles: acute toxic response gene expression profiles. Toxicol In Vitro. 2009 Feb;23(1):67-77.
12 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.
13 A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease. PLoS One. 2013 Sep 27;8(9):e75568.
14 Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP(+). Cell Death Dis. 2014 May 8;5(5):e1222.
15 Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro. Oncotarget. 2014 Dec 30;5(24):12891-907.
16 RNA-Seq of Human Neural Progenitor Cells Exposed to Lead (Pb) Reveals Transcriptome Dynamics, Splicing Alterations and Disease Risk Associations. Toxicol Sci. 2017 Sep 1;159(1):251-265.
17 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297.
18 Acrylamide exposure represses neuronal differentiation, induces cell apoptosis and promotes tau hyperphosphorylation in hESC-derived 3D cerebral organoids. Food Chem Toxicol. 2020 Oct;144:111643.
19 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730.
20 Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma. Cancer Cell. 2017;31(1):50-63.
21 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.
22 Using transcriptomic signatures to elucidate individual and mixture effects of inorganic arsenic and manganese in human placental trophoblast HTR-8/SVneo cells. Toxicol Sci. 2025;203(2):216-226.
23 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
24 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022;449:116110.
25 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.
26 Protein Kinase Signaling Networks Driven by Oncogenic Gq/11 in Uveal Melanoma Identified by Phosphoproteomic and Bioinformatic Analyses. Mol Cell Proteomics. 2023;22(11):100649.
27 Ozone exposure and blood transcriptome: A randomized, controlled, crossover trial among healthy adults. Environ Int. 2022;163:107242.
28 High-Throughput Transcriptomics of Nontumorigenic Breast Cells Exposed to Environmentally Relevant Chemicals. Environ Health Perspect. 2024;132(4):47002.
29 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.
30 Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer. Metallomics. 2012 Aug;4(8):784-93.

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