Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0270 Transporter Info
Gene Name SLC30A10
Transporter Name Zinc transporter 10
Gene ID
55532
UniProt ID
Q6XR72
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Edetic Acid inhibits the reaction SLC30A10 gene mutant form results in increased abundance of Manganese [28]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 NOG protein co-treated with Vorinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC30A10 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Calcitriol promotes the reaction VDR protein binds to RXRA protein which binds to SLC30A10 promoter [7]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Calcitriol results in increased activity of VDR protein which results in increased expression of SLC30A10 mRNA [7]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 NOG protein co-treated with Phenylmercuric Acetate co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC30A10 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Benzo(a)pyrene affects the methylation of SLC30A10 5' UTR [25]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene affects the methylation of SLC30A10 promoter [25]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Benzo(a)pyrene results in increased methylation of SLC30A10 exon [25]

Regulation Mechanism

 Transcription Factor Info

  1-Methyl-4-phenylpyridinium

            3 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 SLC30A10 mRNA [12]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 ATF4 protein promotes the reaction 1-Methyl-4-phenylpyridinium results in increased expression of SLC30A10 mRNA [12]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 SLC30A10 protein results in decreased susceptibility to 1-Methyl-4-phenylpyridinium [12]

Regulation Mechanism

 Transcription Factor Info

  2,2-dithiobis(4,6-dichlorophenol)

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

  DT Modulation1

 SLC30A10 gene SNP affects the susceptibility to 2,2-dithiobis(4,6-dichlorophenol) [19]

Regulation Mechanism

 Transcription Factor Info

  3-iodothyronamine

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

  DT Modulation1

 SLC30A10 mRNA affects the uptake of 3-iodothyronamine [20]

Regulation Mechanism

 Transcription Factor Info

  4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide

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

  DT Modulation1

 NOG protein co-treated with Phenylmercuric Acetate co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC30A10 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 NOG protein co-treated with trichostatin A co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC30A10 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 NOG protein co-treated with Vorinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC30A10 mRNA [21]

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 SLC30A10 mRNA [24]

Regulation Mechanism

 Transcription Factor Info

  beta-Naphthoflavone

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

  DT Modulation1

 beta-Naphthoflavone results in decreased expression of SLC30A10 mRNA [26]

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 affects the expression of SLC30A10 mRNA [15]

Regulation Mechanism

 Transcription Factor Info

  ciglitazone

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

  DT Modulation1

 ciglitazone binds to PPARG protein alternative form which results in increased expression of SLC30A10 mRNA [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 ciglitazone binds to PPARG protein which results in increased expression of SLC30A10 mRNA [27]

Regulation Mechanism

 Transcription Factor Info

  dorsomorphin

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

  DT Modulation1

 NOG protein co-treated with Phenylmercuric Acetate co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC30A10 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 NOG protein co-treated with trichostatin A co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC30A10 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 NOG protein co-treated with Vorinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC30A10 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  GW 501516

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

  DT Modulation1

 GW 501516 binds to PPARD protein which results in increased expression of SLC30A10 mRNA [27]

Regulation Mechanism

 Transcription Factor Info

  Manganese

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

  DT Modulation1

 Edetic Acid inhibits the reaction SLC30A10 gene mutant form results in increased abundance of Manganese [28]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 IL6 protein results in decreased expression of SLC30A10 mRNA which results in decreased export of Manganese [29]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 IL6 protein results in decreased expression of SLC30A10 protein which results in decreased export of Manganese [29]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation4

 SLC30A10 gene mutant form results in increased abundance of Manganese [28]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation5

 SLC30A10 gene SNP affects the transport of Manganese [30]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation6

 SLC30A10 gene SNP results in decreased abundance of Manganese [31]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation7

 SLC30A10 gene SNP results in increased abundance of Manganese [31]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation8

 SLC30A10 protein results in increased secretion of Manganese [32]

Regulation Mechanism

 Transcription Factor Info

  Okadaic Acid

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

  DT Modulation1

 Okadaic Acid results in decreased expression of SLC30A10 mRNA [33]

Regulation Mechanism

 Transcription Factor Info

  pirinixic acid

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

  DT Modulation1

 pirinixic acid binds to and results in increased activity of PPARA protein which results in increased expression of SLC30A10 mRNA [34]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenite

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

  DT Modulation1

 sodium arsenite results in decreased expression of SLC30A10 mRNA [14]

Regulation Mechanism

 Transcription Factor Info

  Tetrachlorodibenzodioxin

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

  DT Modulation1

 Tetrachlorodibenzodioxin results in decreased expression of SLC30A10 mRNA [10]

Regulation Mechanism

 Transcription Factor Info

  trichostatin A

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

  DT Modulation1

 NOG protein co-treated with trichostatin A co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC30A10 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 trichostatin A results in increased expression of SLC30A10 mRNA [36]

Regulation Mechanism

 Transcription Factor Info

  Zinc

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

  DT Modulation1

 SLC30A10 protein results in decreased susceptibility to Zinc [37]

Regulation Mechanism

 Transcription Factor Info

Natural Product

  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 decreased expression of SLC30A10 mRNA [35]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  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 SLC30A10 [1]

  Isotretinoin

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

  DT Modulation1

 Isotretinoin inhibits the expression of SLC30A10 [2]

  Azathioprine

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

  DT Modulation1

 Azathioprine inhibits the expression of SLC30A10 [4]

  Tretinoin

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

  DT Modulation1

 Tretinoin inhibits the expression of SLC30A10 [5]

  Vorinostat

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

  DT Modulation1

 Vorinostat increases the expression of SLC30A10 [6]

  Calcitriol

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

  DT Modulation1

 Calcitriol increases the expression of SLC30A10 [7]

  Rifampin

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

  DT Modulation1

 Rifampin inhibits the expression of SLC30A10 [8]

  Acetaminophen

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

  DT Modulation1

 Acetaminophen inhibits the expression of SLC30A10 [9]

  Estradiol

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

  DT Modulation1

 Estradiol inhibits the expression of SLC30A10 [10]

  Cyclosporine

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

  DT Modulation1

 Cyclosporine inhibits the expression of SLC30A10 [11]

Drug Marketed but not Approved by US FDA

  Edetic Acid

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

  DT Modulation1

 Edetic Acid increases the expression of SLC30A10 [3]

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 affects the expression of SLC30A10 [15]

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 inhibits the expression of SLC30A10 [10]

  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 SLC30A10 [14]

  Trichostatin A

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

  DT Modulation1

 Trichostatin A increases the expression of SLC30A10 [6]

Investigative Drug

  Phenylmercuric Acetate

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

  DT Modulation1

 Phenylmercuric Acetate increases the expression of SLC30A10 [6]

  Beta-naphthoflavone

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

  DT Modulation1

 Beta-naphthoflavone inhibits the expression of SLC30A10 [26]

Regulation Mechanism

 via enhancement of Aryl hydrocarbon receptor (AHR) Transcription Factor Info

Affected Drug/Substrate

 Zinc Modulation Type Inhibition

Cell System

 Human hepatoblastoma cells (HepG2)

Plant Extract

  Grape Seed Proanthocyanidins

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

  DT Modulation1

 Grape Seed Proanthocyanidins inhibits the expression of SLC30A10 [13]

Environmental toxicant

  Polychlorinated dibenzodioxin

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

  DT Modulation1

 Polychlorinated dibenzodioxin inhibits the expression of SLC30A10 [18]

Mycotoxins

  Aflatoxin B1

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

  DT Modulation1

 Aflatoxin B1 inhibits the expression of SLC30A10 [17]

  DT Modulation2

 Aflatoxin B1 affects the expression of SLC30A10 protein [22]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Aflatoxin B1 results in decreased methylation of SLC30A10 gene [23]

Regulation Mechanism

 Transcription Factor Info

Acute Toxic Substance

  Oxyquinoline

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

  DT Modulation1

 Oxyquinoline inhibits the expression of SLC30A10 [10]

Carcinogen

  Benzo(a)pyrene

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

  DT Modulation1

 Benzo(a)pyrene inhibits the expression of SLC30A10 [16]

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 SLC30A10 [12]

Regulation Mechanism

 via enhancement of Cyclic AMP-dependent transcription factor ATF-4 (ATF4) Transcription Factor Info

Cell System

 C57BL/6N mice
References
1 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
2 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
3 Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease. Am J Hum Genet. 2012 Mar 9;90(3):467-77.
4 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
5 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
6 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.
7 Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor. J Steroid Biochem Mol Biol. 2016 Oct;163:77-87.
8 Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
9 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
10 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.
11 Integrative "-Omics" Analysis in Primary Human Hepatocytes Unravels Persistent Mechanisms of Cyclosporine A-Induced Cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
12 Protective function of SLC30A10 induced via PERK-ATF4 pathway against 1-methyl-4-phenylpyridinium. Biochem Biophys Res Commun. 2017 Sep 2;490(4):1307-1313.
13 Dietary catechins and procyanidins modulate zinc homeostasis in human HepG2 cells. J Nutr Biochem. 2011 Feb;22(2):153-63.
14 Cellular and Molecular Effects of Prolonged Low-Level Sodium Arsenite Exposure on Human Hepatic HepaRG Cells. Toxicol Sci. 2018 Apr 1;162(2):676-687.
15 Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134.
16 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297.
17 Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):176-87.
18 The cutaneous lesions of dioxin exposure: lessons from the poisoning of Victor Yushchenko. Toxicol Sci. 2012 Jan;125(1):310-7.
19 Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015;123(5):458-66.
20 Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.
21 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.
22 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.
23 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
24 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.
25 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
26 beta-Naphthoflavone, an exogenous ligand of aryl hydrocarbon receptor, disrupts zinc homeostasis in human hepatoma HepG2 cells. J Toxicol Sci. 2019;44(10):711-720.
27 Gene expression profiling of potential peroxisome proliferator-activated receptor (PPAR) target genes in human hepatoblastoma cell lines inducibly expressing different PPAR isoforms. Nucl Recept. 2005;3:3.
28 Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder. Mov Disord. 2012;27(10):1317-22.
29 Interleukin-6 enhances manganese accumulation in SH-SY5Y cells: implications of the up-regulation of ZIP14 and the down-regulation of ZnT10. Metallomics. 2014;6(4):944-9.
30 Genome-wide association study of toxic metals and trace elements reveals novel associations. Hum Mol Genet. 2015;24(16):4739-45.
31 Common Polymorphisms in the Solute Carrier SLC30A10 are Associated With Blood Manganese and Neurological Function. Toxicol Sci. 2016;149(2):473-83.
32 Hypothyroidism induced by loss of the manganese efflux transporter SLC30A10 may be explained by reduced thyroxine production. J Biol Chem. 2017;292(40):16605-16615.
33 A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells. Arch Toxicol. 2024;98(9):2919-2935.
34 Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human. PLoS One. 2009;4(8):e6796.
35 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.
36 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
37 Angiotensin II requires zinc and downregulation of the zinc transporters ZnT3 and ZnT10 to induce senescence of vascular smooth muscle cells. PLoS One. 2012;7(3):e33211.

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