Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0087 Transporter Info
Gene Name SLC12A6
Transporter Name Electroneutral potassium-chloride cotransporter 3
Gene ID
9990
UniProt ID
Q9UHW9
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Mycotoxins

  Aflatoxin B1

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

  DT Modulation1

 Aflatoxin B1 results in increased methylation of SLC12A6 gene [15]

Regulation Mechanism

 Transcription Factor Info

Chemical Compound

  DT Modulation1

 Cyclosporine results in increased expression of SLC12A6 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  apicidin

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

  DT Modulation1

 apicidin results in increased expression of SLC12A6 mRNA [9]

Regulation Mechanism

 Transcription Factor Info

  avobenzone

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

  DT Modulation1

 avobenzone results in increased expression of SLC12A6 mRNA [6]

Regulation Mechanism

 Transcription Factor Info

  Benzo(a)pyrene

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

  DT Modulation1

 Benzo(a)pyrene results in increased methylation of SLC12A6 promoter [17]

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 results in increased expression of SLC12A6 mRNA [11]

Regulation Mechanism

 Transcription Factor Info

  Cadmium Chloride

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

  DT Modulation1

 Cadmium Chloride results in decreased expression of SLC12A6 mRNA [9]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Cadmium Chloride results in increased expression of SLC12A6 mRNA [18]

Regulation Mechanism

 Transcription Factor Info

  CGP 52608

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

  DT Modulation1

 CGP 52608 promotes the reaction RORA protein binds to SLC12A6 gene [20]

Regulation Mechanism

 Transcription Factor Info

  Copper

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

  DT Modulation1

 NSC 689534 binds to Copper which results in increased expression of SLC12A6 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  dimethylarsinous acid

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

  DT Modulation1

 dimethylarsinous acid results in increased expression of SLC12A6 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

  Dimethylnitrosamine

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

  DT Modulation1

 Dimethylnitrosamine results in increased expression of SLC12A6 mRNA [1]

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 SLC12A6 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

  Estradiol

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

  DT Modulation1

 Estradiol co-treated with Norethindrone Acetate results in increased expression of SLC12A6 mRNA [24]

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 SLC12A6 protein [25]

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 SLC12A6 mRNA [16]

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 SLC12A6 mRNA [16]

Regulation Mechanism

 Transcription Factor Info

  methylmercuric chloride

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

  DT Modulation1

 methylmercuric chloride results in decreased expression of SLC12A6 mRNA [26]

Regulation Mechanism

 Transcription Factor Info

  Methyl Methanesulfonate

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

  DT Modulation1

 Methyl Methanesulfonate results in increased expression of SLC12A6 mRNA [27]

Regulation Mechanism

 Transcription Factor Info

  Norethindrone Acetate

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

  DT Modulation1

 Estradiol co-treated with Norethindrone Acetate results in increased expression of SLC12A6 mRNA [24]

Regulation Mechanism

 Transcription Factor Info

  NSC 689534

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

  DT Modulation1

 NSC 689534 binds to Copper which results in increased expression of SLC12A6 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 NSC 689534 results in increased expression of SLC12A6 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  oxamflatin

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

  DT Modulation1

 oxamflatin results in increased expression of SLC12A6 mRNA [9]

Regulation Mechanism

 Transcription Factor Info

  perfluorooctanoic acid

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

  DT Modulation1

 perfluorooctanoic acid results in increased expression of SLC12A6 protein [28]

Regulation Mechanism

 Transcription Factor Info

  potassium chromate(VI)

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

  DT Modulation1

 potassium chromate(VI) results in decreased expression of SLC12A6 mRNA [29]

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 decreased expression of SLC12A6 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 sodium arsenite results in increased abundance of Arsenic co-treated with manganese chloride results in increased abundance of Manganese results in decreased expression of SLC12A6 mRNA [16]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 sodium arsenite results in increased expression of SLC12A6 mRNA [31]

Regulation Mechanism

 Transcription Factor Info

  Thalidomide

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

  DT Modulation1

 SLC12A6 gene SNP results in increased susceptibility to Thalidomide [32]

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 SLC12A6 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Cyclosporine

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

  DT Modulation1

 Cyclosporine inhibits the expression of SLC12A6 [2]

  Urethane

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

  DT Modulation1

 Urethane increases the expression of SLC12A6 [3]

  Dronabinol

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

  DT Modulation1

 Dronabinol increases the expression of SLC12A6 [4]

  Doxorubicin

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

  DT Modulation1

 Doxorubicin inhibits the expression of SLC12A6 [5]

  Avobenzone

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

  DT Modulation1

 Avobenzone increases the expression of SLC12A6 [6]

  Tretinoin

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

  DT Modulation1

 Tretinoin increases the expression of SLC12A6 [7]

  Testosterone

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

  DT Modulation1

 Testosterone inhibits the expression of SLC12A6 [8]

  Cytarabine

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

  DT Modulation1

 Cytarabine inhibits the expression of SLC12A6 [9]

Drug in Phase 2/3 Trial

  Phenol

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

  DT Modulation1

 Phenol increases the expression of SLC12A6 [1]

Drug in Phase 2 Trial

  Bisphenol A

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

  DT Modulation1

 Bisphenol A increases the expression of SLC12A6 [11]

Drug in Phase 1 Trial

  Sodium arsenite

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

  DT Modulation1

 Sodium arsenite inhibits the expression of SLC12A6 [13]

Drug in Preclinical Test

  (+)-JQ1

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

  DT Modulation1

 (+)-JQ1 increases the expression of SLC12A6 [14]

Patented Pharmaceutical Agent

  NSC-689534

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

  DT Modulation1

 NSC-689534 increases the expression of SLC12A6 [10]

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 SLC12A6 [12]

  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 SLC12A6 protein [19]

Regulation Mechanism

 Transcription Factor Info

  Quercetin

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

  DT Modulation1

 Quercetin results in increased phosphorylation of SLC12A6 protein [19]

Regulation Mechanism

 Transcription Factor Info

  Resveratrol

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

  DT Modulation1

 Plant Extracts co-treated with Resveratrol results in increased expression of SLC12A6 mRNA [30]

Regulation Mechanism

 Transcription Factor Info

Carcinogen

  Dimethyl nitrosamine

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

  DT Modulation1

 Dimethyl nitrosamine increases the expression of SLC12A6 [1]

  Arsenic

            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 SLC12A6 mRNA [16]

Regulation Mechanism

 Transcription Factor Info
References
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2 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.
3 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
4 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89.
5 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.
6 A long-wave UVA filter avobenzone induces obesogenic phenotypes in normal human epidermal keratinocytes and mesenchymal stem cells. Arch Toxicol. 2019 Jul;93(7):1903-1915.
7 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423.
8 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384.
9 Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645.
10 A copper chelate of thiosemicarbazone NSC 689534 induces oxidative/ER stress and inhibits tumor growth in vitro and in vivo. Free Radic Biol Med. 2011 Jan 1;50(1):110-21.
11 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
12 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.
13 Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer. Arch Toxicol. 2021 Jul;95(7):2351-2365.
14 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
15 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
16 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.
17 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
18 Evaluation of Cd-induced cytotoxicity in primary human keratinocytes. Hum Exp Toxicol. 2024;43:9603271231224458.
19 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022;449:116110.
20 Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
21 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
22 Transcriptional Modulation of the ERK1/2 MAPK and NF-B Pathways in Human Urothelial Cells After Trivalent Arsenical Exposure: Implications for Urinary Bladder Cancer. J Can Res Updates. 2012;1:57-68.
23 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.
24 A microarray study on the effect of four hormone therapy regimens on gene transcription in whole blood from healthy postmenopausal women. Thromb Res. 2012;130(1):45-51.
25 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.
26 Stem Cell Transcriptome Responses and Corresponding Biomarkers That Indicate the Transition from Adaptive Responses to Cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
27 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
28 High perfluorooctanoic acid exposure induces autophagy blockage and disturbs intracellular vesicle fusion in the liver. Arch Toxicol. 2017;91(1):247-258.
29 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.
30 One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69-82.
31 High-Throughput Transcriptomics of Nontumorigenic Breast Cells Exposed to Environmentally Relevant Chemicals. Environ Health Perspect. 2024;132(4):47002.
32 Genetic factors underlying the risk of thalidomide-related neuropathy in patients with multiple myeloma. J Clin Oncol. 2011;29(7):797-804.

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