Gene info: ID 6559

Gene: SLC12A3

GENE ID: 6559

Synonyms: NCC|NCCT|TSC

Description: solute carrier family 12 member 3

Gene type: protein-coding

Location: 16q13

dbXrefs: Ensembl:ENSG00000070915 MIM:600968 Vega:OTTHUMG00000133284 UniprotKB:P55017

RefSeq: NG_009386.1

Retrived from: PubMed

SNPs: 0 ANCO-SNPs

Phenotype: ND

# Publications: 1

Sherlock p-value : NA (AD) NA (ND) (Frontal_Cortex)

Pascal p-value : 9.698e-1 (AD) 5.741e-1 (ND)

DNA Methylation

Probe	Locus(GRCh37)	Gene	Region	p-val	Trait	PubMed ID
cg26973177	chr16:56898967	SLC12A3	Promoter	9.428e-5	Alcohol use disorders	26763658

Gene Expression in Different Tissues

Temporal and Spatial Expressions (BrainSpan)

Footnote:
SC: sub-cortical regions; SM: sensory-motor regions; FC: frontal cortex; and TP: temporal-parietal cortex
ST1: fetal (13 - 26 postconception weeks), ST2: early infancy to late childhood (4 months to 11 years), and ST3: adolescence to adulthood (13 - 23 years)
The bar shown representes average value of the expressions.

Top Co-expressed Genes in Brain-Frontal Cortex (BA9) (GTEx v7)

Top 10 positively co-expressed genes

Gene Symbol	Pearson Correlation Coefficient
PLEKHG4B	0.639
TNFSF13B	0.544
AOC2	0.537
NPC1L1	0.519
ARID3A	0.517
OR10G8	0.512
PLSCR2	0.512
KRTAP10-8	0.51
IL18BP	0.51
PPEF2	0.508

Top 10 negatively co-expressed genes

Gene Symbol	Pearson Correlation Coefficient
HPDL	-0.397
HSD17B8	-0.385
CYS1	-0.367
ABCD2	-0.362
ENDOU	-0.36
SNX22	-0.35
ALG1L	-0.339
CA14	-0.333
HES5	-0.333
CRH	-0.331

ID	Drug Name	Drug Type	CAS Num	Status	Role
DB00436	Bendroflumethiazide	Small Molecule	73-48-3	Approved	Target
DB00524	Metolazone	Small Molecule	17560-51-9	Approved	Target
DB00562	Benzthiazide	Small Molecule	91-33-8	Approved	Target
DB00880	Chlorothiazide	Small Molecule	58-94-6	Approved	Target
DB00999	Hydrochlorothiazide	Small Molecule	58-93-5	Approved	Target
DB01119	Diazoxide	Small Molecule	364-98-7	Approved	Target
DB01324	Polythiazide	Small Molecule	346-18-9	Approved	Target
DB01325	Quinethazone	Small Molecule	73-49-4	Approved	Target

ID	Drug Name	Action	PubMed
C532162	2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	"2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine inhibits the reaction [INS1 protein results in increased phosphorylation of SLC12A3 protein]"	22949526
D000082	Acetaminophen	Acetaminophen affects the expression of SLC12A3 mRNA	25064622
D000111	Acetylcysteine	[indole-3-carbinol co-treated with Diethylnitrosamine co-treated with Acetylcysteine] results in decreased expression of SLC12A3 mRNA	22129741
D020106	Acrylamide	Acrylamide results in decreased expression of SLC12A3 mRNA	28959563
D000638	Amiodarone	Amiodarone affects the expression of SLC12A3 mRNA	25064622
D000643	Ammonium Chloride	Ammonium Chloride affects the expression of SLC12A3 mRNA	16483693
D018501	Antirheumatic Agents	Antirheumatic Agents results in decreased expression of SLC12A3 mRNA	24449571
D001151	Arsenic	Arsenic affects the methylation of SLC12A3 gene	25304211
D001539	Bendroflumethiazide	SLC12A3 protein results in increased susceptibility to Bendroflumethiazide	18480177
D001539	Bendroflumethiazide	Bendroflumethiazide results in decreased activity of SLC12A3 protein	21963515
D001564	Benzo(a)pyrene	Benzo(a)pyrene promotes the reaction [AHR protein binds to SLC12A3 promoter]	19654925
D004958	Estradiol	Estradiol affects the expression of SLC12A3 mRNA	23557687
C006780	bisphenol A	bisphenol A results in decreased expression of SLC12A3 mRNA	25181051
C006780	bisphenol A	bisphenol A results in increased methylation of SLC12A3 gene	28505145
D002251	Carbon Tetrachloride	Carbon Tetrachloride results in decreased expression of SLC12A3 mRNA	17805973
D002251	Carbon Tetrachloride	Carbon Tetrachloride results in increased expression of SLC12A3 protein	15673309
D002746	Chlorpromazine	Chlorpromazine affects the expression of SLC12A3 mRNA	25064622
D060729	Coal Ash	Coal Ash results in increased expression of SLC12A3 mRNA	19000753
D003471	Cuprizone	Cuprizone results in increased expression of SLC12A3 mRNA	26577399
D016572	Cyclosporine	Cyclosporine affects the expression of SLC12A3 mRNA	25064622
D016572	Cyclosporine	Cyclosporine results in decreased expression of SLC12A3 mRNA	21865292
D016572	Cyclosporine	Cyclosporine results in decreased expression of SLC12A3 protein	21865292
C531198	dactolisib	dactolisib inhibits the reaction [INS1 protein results in increased phosphorylation of SLC12A3 protein]	22949526
C531198	dactolisib	dactolisib results in decreased phosphorylation of SLC12A3 protein	22949526
C010902	decabromobiphenyl ether	decabromobiphenyl ether results in increased expression of SLC12A3 mRNA	23914054
D003907	Dexamethasone	Dexamethasone results in increased expression of SLC12A3 protein	18400872
D003999	Dichloroacetic Acid	Dichloroacetic Acid results in decreased expression of SLC12A3 mRNA	28962523
D004026	Dieldrin	Dieldrin results in increased expression of SLC12A3 mRNA	20438755
D004052	Diethylnitrosamine	[indole-3-carbinol co-treated with Diethylnitrosamine co-treated with Acetylcysteine] results in decreased expression of SLC12A3 mRNA	22129741
D004317	Doxorubicin	Doxorubicin results in decreased expression of SLC12A3 mRNA	19915844
C414690	eplerenone	"[eplerenone co-treated with Sodium Chloride, Dietary] results in decreased phosphorylation of SLC12A3 protein"	22949526
C414690	eplerenone	eplerenone inhibits the reaction [AGT protein results in increased phosphorylation of SLC12A3 protein]	20175999
D004997	Ethinyl Estradiol	Ethinyl Estradiol affects the expression of SLC12A3 mRNA	25064622
D005839	Gentamicins	Gentamicins affects the expression of SLC12A3 protein	16850027
C412815	GW 4064	GW 4064 results in decreased expression of SLC12A3 mRNA	26655953
D006830	Hydralazine	[Hydralazine co-treated with Valproic Acid] results in increased expression of SLC12A3 mRNA	17183730
D006852	Hydrochlorothiazide	Hydrochlorothiazide results in decreased activity of SLC12A3 protein	21963515\|2294952
C016517	indole-3-carbinol	[indole-3-carbinol co-treated with Diethylnitrosamine co-treated with Acetylcysteine] results in decreased expression of SLC12A3 mRNA	22129741
D015759	Ionomycin	[Tetradecanoylphorbol Acetate co-treated with Ionomycin] affects the expression of SLC12A3 mRNA	25613284
D008070	Lipopolysaccharides	Lipopolysaccharides results in increased expression of SLC12A3 mRNA	25613284
D058185	Magnetite Nanoparticles	[Succimer co-treated with Magnetite Nanoparticles] results in decreased expression of SLC12A3 mRNA	26378955
D008627	Mercuric Chloride	Mercuric Chloride results in decreased expression of SLC12A3 protein	16189294
D008694	Methamphetamine	Methamphetamine results in decreased expression of SLC12A3 mRNA	26307267
C004925	methylmercuric chloride	methylmercuric chloride results in increased expression of SLC12A3 mRNA	23458150
D008741	Methyl Methanesulfonate	Methyl Methanesulfonate results in decreased expression of SLC12A3 mRNA	26011545
C548887	MK 2206	MK 2206 inhibits the reaction [INS1 protein results in increased phosphorylation of SLC12A3 protein]	22949526
D010269	Paraquat	Paraquat affects the expression of SLC12A3 mRNA	25064622
D011192	Potassium Dichromate	Potassium Dichromate results in decreased expression of SLC12A3 mRNA	23608068
D011441	Propylthiouracil	Propylthiouracil results in decreased expression of SLC12A3 mRNA	24780913
D011692	Puromycin Aminonucleoside	Puromycin Aminonucleoside results in decreased expression of SLC12A3 protein	15075188
D020123	Sirolimus	Sirolimus results in increased expression of SLC12A3 mRNA	21865292
D017673	Sodium Chloride, Dietary	"[eplerenone co-treated with Sodium Chloride, Dietary] results in decreased phosphorylation of SLC12A3 protein"	22949526
D017673	Sodium Chloride, Dietary	"Sodium Chloride, Dietary deficiency results in increased phosphorylation of SLC12A3 protein"	22949526
D004113	Succimer	[Succimer co-treated with Magnetite Nanoparticles] results in decreased expression of SLC12A3 mRNA	26378955
D016559	Tacrolimus	SLC12A3 protein affects the susceptibility to Tacrolimus	21963515
D016559	Tacrolimus	Tacrolimus results in increased phosphorylation of SLC12A3 protein	21963515
D016559	Tacrolimus	Tacrolimus results in decreased expression of SLC12A3 mRNA	21865292
D016559	Tacrolimus	Tacrolimus results in decreased expression of SLC12A3 protein	21865292
D013749	Tetrachlorodibenzodioxin	Tetrachlorodibenzodioxin affects the expression of SLC12A3 mRNA	21570461
D013752	Tetracycline	Tetracycline affects the expression of SLC12A3 mRNA	25064622
D013755	Tetradecanoylphorbol Acetate	[Tetradecanoylphorbol Acetate co-treated with Ionomycin] affects the expression of SLC12A3 mRNA	25613284
D013853	Thioacetamide	Thioacetamide affects the expression of SLC12A3 mRNA	25064622
D014241	Trichloroethylene	Trichloroethylene results in decreased expression of SLC12A3 mRNA	26745549
D014520	Urethane	Urethane results in decreased expression of SLC12A3 mRNA	28818685
D014635	Valproic Acid	Valproic Acid affects the expression of SLC12A3 mRNA	25064622
D014635	Valproic Acid	[Hydralazine co-treated with Valproic Acid] results in increased expression of SLC12A3 mRNA	17183730
D014635	Valproic Acid	Valproic Acid results in increased methylation of SLC12A3 gene	29154799
D000068756	Valsartan	Valsartan inhibits the reaction [AGT protein results in increased phosphorylation of SLC12A3 protein]	20175999
D014640	Vancomycin	Vancomycin results in increased expression of SLC12A3 mRNA	18930951
C025643	vinclozolin	vinclozolin results in increased expression of SLC12A3 mRNA	23034163
C029297	vinylidene chloride	vinylidene chloride results in decreased expression of SLC12A3 mRNA	26682919
D015215	Zidovudine	Zidovudine results in decreased expression of SLC12A3 mRNA	24292225
D015034	Zinc Oxide	Zinc Oxide analog results in decreased expression of SLC12A3 mRNA	27215404

GO/Pathway

GO ID	GO Term	Qualifier	Evidence	PubMed
GO:0005215	transporter activity	-	ISS	-
GO:0005515	protein binding	-	IPI	22406640
GO:0008511	sodium:potassium:chloride symporter activity	-	IBA	21873635
GO:0015081	sodium ion transmembrane transporter activity	-	IBA	21873635
GO:0015378	sodium:chloride symporter activity	-	IBA	21873635
GO:0015378	sodium:chloride symporter activity	-	TAS	-
GO:0015379	potassium:chloride symporter activity	-	IBA	21873635

GO ID	GO Term	Qualifier	Evidence	PubMed
GO:0006811	ion transport	-	TAS	-
GO:0006814	sodium ion transport	-	ISS	-
GO:0006884	cell volume homeostasis	-	IBA	21873635
GO:0010107	potassium ion import	-	IBA	21873635
GO:0035725	sodium ion transmembrane transport	-	IBA	21873635
GO:0035725	sodium ion transmembrane transport	-	ISS	-
GO:0055064	chloride ion homeostasis	-	IBA	21873635
GO:0055075	potassium ion homeostasis	-	IBA	21873635
GO:0055078	sodium ion homeostasis	-	IBA	21873635
GO:1902476	chloride transmembrane transport	-	IBA	21873635
GO:1902476	chloride transmembrane transport	-	IEA	-

GO ID	GO Term	Qualifier	Evidence	PubMed
GO:0005829	cytosol	-	IEA	-
GO:0005886	plasma membrane	-	TAS	-
GO:0005887	integral component of plasma membrane	-	TAS	8670281
GO:0016020	membrane	-	TAS	8670281
GO:0016324	apical plasma membrane	-	IBA	21873635
GO:0016324	apical plasma membrane	-	IDA	21397062
GO:0016324	apical plasma membrane	-	ISS	-
GO:0070062	extracellular exosome	-	HDA	19056867 23533145
GO:0070062	extracellular exosome	-	IDA	21082674

KEGG ID	KEGG Term

Reactome ID	Reactome Term	Evidence
R-HSA-1643685	Disease	TAS
R-HSA-382551	Transport of small molecules	TAS
R-HSA-425393	Transport of inorganic cations/anions and amino acids/oligopeptides	TAS
R-HSA-425407	SLC-mediated transmembrane transport	TAS
R-HSA-426117	Cation-coupled Chloride cotransporters	TAS
R-HSA-5619087	Defective SLC12A3 causes Gitelman syndrome (GS)	TAS
R-HSA-5619102	SLC transporter disorders	TAS
R-HSA-5619115	Disorders of transmembrane transporters	TAS

Interactions (STRING v10.5, Interaction Score >= 0.400)

Publications (Co-occurrence of gene symbol strings and ANCO-Dependence terms)

PMID	Title (Year)	Author	Journal
15309683	Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population. (2004)	Kokubo Y	J Hum Genet