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Aliases for SLC12A3 Gene

Aliases for SLC12A3 Gene

  • Solute Carrier Family 12 (Sodium/Chloride Transporter), Member 3 2 3
  • TSC 3 4 6
  • Thiazide-Sensitive Sodium-Chloride Cotransporter 3 4
  • Na-Cl Cotransporter 3 4
  • Na-Cl Symporter 3 4
  • NCCT 3 6
  • NCC 3 4
  • NaCl Electroneutral Thiazide-Sensitive Cotransporter 3
  • Thiazide-Sensitive Na-Cl Cotransporter 3
  • Solute Carrier Family 12 Member 3 3

External Ids for SLC12A3 Gene

Previous GeneCards Identifiers for SLC12A3 Gene

  • GC16M047352
  • GC16P056950
  • GC16P056633
  • GC16P056675
  • GC16P056676
  • GC16P055456
  • GC16P042768

Summaries for SLC12A3 Gene

Entrez Gene Summary for SLC12A3 Gene

  • This gene encodes a renal thiazide-sensitive sodium-chloride cotransporter that is important for electrolyte homeostasis. This cotransporter mediates sodium and chloride reabsorption in the distal convoluted tubule. Mutations in this gene cause Gitelman syndrome, a disease similar to Bartter's syndrome, that is characterized by hypokalemic alkalosis combined with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. This cotransporter is the target for thiazide diuretics that are used for treating high blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for SLC12A3 Gene

SLC12A3 (Solute Carrier Family 12 (Sodium/Chloride Transporter), Member 3) is a Protein Coding gene. Diseases associated with SLC12A3 include gitelman syndrome and renal hypertension. Among its related pathways are Diuretics Pathway, Pharmacodynamics and Neuropathic Pain-Signaling in Dorsal Horn Neurons. GO annotations related to this gene include transporter activity and sodium:chloride symporter activity. An important paralog of this gene is SLC12A2.

UniProtKB/Swiss-Prot for SLC12A3 Gene

  • Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.

Gene Wiki entry for SLC12A3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SLC12A3 Gene

Genomics for SLC12A3 Gene

Regulatory Elements for SLC12A3 Gene

Genomic Location for SLC12A3 Gene

Start:
56,865,207 bp from pter
End:
56,915,850 bp from pter
Size:
50,644 bases
Orientation:
Plus strand

Genomic View for SLC12A3 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SLC12A3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC12A3 Gene

Proteins for SLC12A3 Gene

  • Protein details for SLC12A3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P55017-S12A3_HUMAN
    Recommended name:
    Solute carrier family 12 member 3
    Protein Accession:
    P55017
    Secondary Accessions:
    • A8MSJ2
    • C9JNN9

    Protein attributes for SLC12A3 Gene

    Size:
    1021 amino acids
    Molecular mass:
    113139 Da
    Quaternary structure:
    • Interacts with KLHL3.
    Miscellaneous:
    • Target of thiazide diuretics used in the treatment of high blood pressure.

    Alternative splice isoforms for SLC12A3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SLC12A3 Gene

Proteomics data for SLC12A3 Gene at MOPED

Post-translational modifications for SLC12A3 Gene

  • Ubiquitinated; ubiquitination is essential for regulation of endocytosis. The BCR(KLHL3) complex was initially identified as a candidate ubiquitin ligase for SLC12A3 (PubMed:22406640). However, it was later shown that it is not the case.
  • Glycosylation at Asn406 and Asn426
  • Modification sites at PhosphoSitePlus

Other Protein References for SLC12A3 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for SLC12A3 Gene

Domains for SLC12A3 Gene

Gene Families for SLC12A3 Gene

Suggested Antigen Peptide Sequences for SLC12A3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P55017

UniProtKB/Swiss-Prot:

S12A3_HUMAN :
  • P55017
Family:
  • Belongs to the SLC12A transporter family.
genes like me logo Genes that share domains with SLC12A3: view

Function for SLC12A3 Gene

Molecular function for SLC12A3 Gene

GENATLAS Biochemistry: solute carrier family 12,member A3,sodium/chloride transporter
UniProtKB/Swiss-Prot EnzymeRegulation: Activated by WNK3.
UniProtKB/Swiss-Prot Function: Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.

Gene Ontology (GO) - Molecular Function for SLC12A3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005215 transporter activity ISS --
GO:0005515 protein binding IPI 22406640
GO:0015377 cation:chloride symporter activity --
GO:0015378 sodium:chloride symporter activity TAS 8528245
genes like me logo Genes that share ontologies with SLC12A3: view
genes like me logo Genes that share phenotypes with SLC12A3: view

Animal Models for SLC12A3 Gene

MGI Knock Outs for SLC12A3:

miRNA for SLC12A3 Gene

miRTarBase miRNAs that target SLC12A3

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for SLC12A3 Gene

Localization for SLC12A3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC12A3 Gene

Cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SLC12A3 Gene COMPARTMENTS Subcellular localization image for SLC12A3 gene
Compartment Confidence
plasma membrane 5
cytosol 2
nucleus 1

Gene Ontology (GO) - Cellular Components for SLC12A3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol IEA --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 8670281
GO:0016020 membrane TAS 8670281
GO:0016021 integral component of membrane --
genes like me logo Genes that share ontologies with SLC12A3: view

Pathways for SLC12A3 Gene

genes like me logo Genes that share pathways with SLC12A3: view

Gene Ontology (GO) - Biological Process for SLC12A3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport TAS 8528245
GO:0006811 ion transport TAS --
GO:0006814 sodium ion transport ISS --
GO:0006821 chloride transport TAS 8528245
GO:0035725 sodium ion transmembrane transport ISS --
genes like me logo Genes that share ontologies with SLC12A3: view

Compounds for SLC12A3 Gene

(4) HMDB Compounds for SLC12A3 Gene

Compound Synonyms Cas Number PubMed IDs
Calcium
  • Ca
7440-70-2
Chlorine
  • Cl2
16887-00-6
Hydrochlorothiazide
  • 3,4-Dihydrochlorothiazide
58-93-5
Sodium
  • Sodium
7440-23-5

(8) Drugbank Compounds for SLC12A3 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Bendroflumethiazide
  • Bendrofluazide
73-48-3 target inhibitor
Benzthiazide
91-33-8 target inhibitor
Chlorothiazide
  • Chlorothiazid
58-94-6 target inhibitor
Diazoxide
364-98-7 target unknown
Hydrochlorothiazide
  • Dihydrochlorothiazid
58-93-5 target inhibitor

(3) IUPHAR Ligand for SLC12A3 Gene

Ligand Type Action Affinity Pubmed IDs
hydrochlorothiazide Inhibitor Inhibition
chlorothiazide Inhibitor Inhibition
metolazone Inhibitor Inhibition

(15) Novoseek inferred chemical compound relationships for SLC12A3 Gene

Compound -log(P) Hits PubMed IDs
thiazide 86.7 34
nacl 76.5 59
chloride 69.2 6
potassium 65.4 7
sodium 59.3 16

(1) PharmGKB related drug/compound annotations for SLC12A3 Gene

Drug/compound Annotation
"Thiazides, plain" CA
genes like me logo Genes that share compounds with SLC12A3: view

Transcripts for SLC12A3 Gene

Unigene Clusters for SLC12A3 Gene

Solute carrier family 12 (sodium/chloride transporters), member 3:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SLC12A3 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20a · 20b ^ 21 ^ 22 ^ 23 ^ 24a ·
SP1: -
SP2: - -
SP3:
SP4:
SP5:

ExUns: 24b ^ 25a · 25b ^ 26 ^ 27a · 27b · 27c
SP1: - -
SP2: - -
SP3:
SP4:
SP5:

Relevant External Links for SLC12A3 Gene

GeneLoc Exon Structure for
SLC12A3
ECgene alternative splicing isoforms for
SLC12A3

Expression for SLC12A3 Gene

mRNA expression in normal human tissues for SLC12A3 Gene

mRNA differential expression in normal tissues according to GTEx for SLC12A3 Gene

This gene is overexpressed in Kidney - Cortex (50.4).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for SLC12A3 Gene

SOURCE GeneReport for Unigene cluster for SLC12A3 Gene Hs.669115

mRNA Expression by UniProt/SwissProt for SLC12A3 Gene

P55017-S12A3_HUMAN
Tissue specificity: Predominant in kidney
genes like me logo Genes that share expressions with SLC12A3: view

Orthologs for SLC12A3 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for SLC12A3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SLC12A3 35
  • 99.42 (n)
  • 99.32 (a)
SLC12A3 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SLC12A3 35
  • 90.23 (n)
  • 92.82 (a)
SLC12A3 36
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SLC12A3 35
  • 90.55 (n)
  • 93.69 (a)
SLC12A3 36
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Slc12a3 35
  • 87.08 (n)
  • 91.61 (a)
Slc12a3 16
Slc12a3 36
  • 92 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SLC12A3 36
  • 86 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SLC12A3 36
  • 58 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Slc12a3 35
  • 87.49 (n)
  • 91.42 (a)
chicken
(Gallus gallus)
Aves SLC12A3 35
  • 77.88 (n)
  • 79.03 (a)
SLC12A3 36
  • 78 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SLC12A3 36
  • 78 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.25160 35
tropical clawed frog
(Silurana tropicalis)
Amphibia slc12a3 35
  • 69.77 (n)
  • 75.24 (a)
zebrafish
(Danio rerio)
Actinopterygii slc12a3 35
  • 64.93 (n)
  • 65.3 (a)
slc12a3 36
  • 63 (a)
OneToOne
wufj83c03 35
fruit fly
(Drosophila melanogaster)
Insecta CG31547 36
  • 38 (a)
ManyToMany
Ncc69 36
  • 36 (a)
ManyToMany
EG:8D8.3 37
  • 32 (a)
worm
(Caenorhabditis elegans)
Secernentea B0303.11 36
  • 25 (a)
ManyToMany
nkcc-1 36
  • 35 (a)
ManyToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 36
  • 22 (a)
OneToMany
Species with no ortholog for SLC12A3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SLC12A3 Gene

ENSEMBL:
Gene Tree for SLC12A3 (if available)
TreeFam:
Gene Tree for SLC12A3 (if available)

Paralogs for SLC12A3 Gene

Paralogs for SLC12A3 Gene

Selected SIMAP similar genes for SLC12A3 Gene using alignment to 3 proteins:

Pseudogenes.org Pseudogenes for SLC12A3 Gene

genes like me logo Genes that share paralogs with SLC12A3: view

Variants for SLC12A3 Gene

Sequence variations from dbSNP and Humsavar for SLC12A3 Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type MAF
rs5801 -- 56,879,601(+) GCCAC(C/T)CTCTC reference, synonymous-codon
rs5802 -- 56,885,323(+) TACTC(A/C/G)GTGGG synonymous-codon, reference
rs5803 -- 56,887,057(+) ATTGC(C/T)GAGGA reference, synonymous-codon
rs5804 -- 56,894,607(+) GTAGG(C/T)GGCCA reference, synonymous-codon
rs5805 -- 56,913,610(-) TAGCC(C/T)ATAAA utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for SLC12A3 Gene

Variant ID Type Subtype PubMed ID
esv33108 CNV Loss 17666407
dgv2871n71 CNV Loss 21882294
nsv526264 CNV Loss 19592680
nsv519897 CNV Loss 19592680

Relevant External Links for SLC12A3 Gene

HapMap Linkage Disequilibrium report
SLC12A3
Human Gene Mutation Database (HGMD)
SLC12A3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLC12A3 Gene

Disorders for SLC12A3 Gene

MalaCards: The human disease database

MalaCards: The human disease database. (8) Diseases for SLC12A3 Gene including...

Search for SLC12A3 Gene in MalaCards »

(1) OMIM Diseases for SLC12A3 Gene (600968)

UniProtKB/Swiss-Prot

S12A3_HUMAN
  • Gitelman syndrome (GS) [MIM:263800]: An autosomal recessive disorder characterized by hypokalemic alkalosis in combination with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. Patients are often asymptomatic or present transient periods of muscular weakness and tetany, usually accompanied by abdominal pain, vomiting and fever. The phenotype is highly heterogeneous in terms of age at onset and severity. Cardinal features such as hypocalciuria and hypomagnesemia might also change during the life cycle of a given patient. It has overlapping features with Bartter syndrome. {ECO:0000269 PubMed:10616841, ECO:0000269 PubMed:10988270, ECO:0000269 PubMed:11168953, ECO:0000269 PubMed:11940055, ECO:0000269 PubMed:12008755, ECO:0000269 PubMed:12112667, ECO:0000269 PubMed:15069170, ECO:0000269 PubMed:15687331, ECO:0000269 PubMed:16429844, ECO:0000269 PubMed:17654016, ECO:0000269 PubMed:17873326, ECO:0000269 PubMed:8528245, ECO:0000269 PubMed:8900229, ECO:0000269 PubMed:8954067, ECO:0000269 PubMed:9734597}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(22) Novoseek inferred disease relationships for SLC12A3 Gene

Disease -log(P) Hits PubMed IDs
gitelman syndrome 98.8 96
bartters syndrome 94.9 8
hypomagnesemia 93.8 15
metabolic alkalosis 93.7 10
bartter syndrome, classic 93.6 2

Genatlas disease for SLC12A3 Gene

Gitelman syndrome characterized by an hypokalemic alkalosis Bartter-like associated with hypocalciuria and hypomagnesemia

Relevant External Links for SLC12A3

Genetic Association Database (GAD)
SLC12A3
Human Genome Epidemiology (HuGE) Navigator
SLC12A3
genes like me logo Genes that share disorders with SLC12A3: view

Publications for SLC12A3 Gene

  1. Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome. (PMID: 15069170) Maki N. … Sawada K. (Nephrol. Dial. Transplant. 2004) 3 4 23 25 48
  2. Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3). (PMID: 8812482) Mastroianni N. … Casari G. (Genomics 1996) 2 3 4 23
  3. G2736A polymorphism of thiazide-sensitive Na-Cl cotransporter gene predisposes to hypertension in young women. (PMID: 15480096) Matsuo A. … Ogihara T. (J. Hypertens. 2004) 3 23 48
  4. The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics. (PMID: 15824464) Matayoshi T. … Kawano Y. (Hypertens. Res. 2004) 3 23 48
  5. Polymorphism of the solute carrier family 12 (sodium/chloride transporters) member 3, SLC12A3, gene at exon 23 (+78G/A: Arg913Gln) is associated with elevation of urinary albumin excretion in Japanese patients with type 2 diabetes: a 10-year longitudinal study. (PMID: 15915338) Nishiyama K. … Kawamori R. (Diabetologia 2005) 3 23 48

Products for SLC12A3 Gene

Sources for SLC12A3 Gene

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