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Aliases for SLC12A3 Gene

Aliases for SLC12A3 Gene

  • Solute Carrier Family 12 Member 3 2 3 5
  • Solute Carrier Family 12 (Sodium/Chloride Transporter), Member 3 2 3
  • Thiazide-Sensitive Sodium-Chloride Cotransporter 3 4
  • Na-Cl Cotransporter 3 4
  • Na-Cl Symporter 3 4
  • NCC 3 4
  • TSC 3 4
  • NaCl Electroneutral Thiazide-Sensitive Cotransporter 3
  • Thiazide-Sensitive Na-Cl Cotransporter 3
  • NCCT 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 Member 3) is a Protein Coding gene. Diseases associated with SLC12A3 include Gitelman Syndrome and Hypokalemia. Among its related pathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Diuretics Pathway, Pharmacodynamics. 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

  • Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (PubMed:21613606, PubMed:22009145). Receptor for the proinflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).

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

Enhancers for SLC12A3 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH16F056805 0.9 Ensembl ENCODE 16.1 -58.3 -58274 2.2 GATAD2A SOX5 TEAD1 JUN HMG20A EP300 RFX5 ZNF664 GATA3 JUND SLC12A3 NUDT21 MT1G MT1H MIR138-2 NUP93 MT1B NLRC5 MT1X MT1F
GH16F056930 0.5 ENCODE 11.4 +70.3 70312 10.1 MLX CREB3L1 ZFP64 FEZF1 DMAP1 YY1 SLC30A9 ZNF416 ZNF143 SP3 RSPRY1 NUDT21 NUP93 BBS2 POLR2C CETP SLC12A3 ENSG00000261270 NLRC5 LOC105371286
GH16F056800 0.2 ENCODE 11 -64.6 -64559 0.6 GATAD2A ELF3 SAP130 TEAD1 NR2F1 PPARG RAD21 NR2F2 RARA TEAD3 MIR138-2 SLC12A3 NUP93 MT1G MT1H MT1X MT1B NLRC5 BBS2 HERPUD1
GH16F056858 0.6 Ensembl ENCODE 6.2 -4.2 -4208 5.6 HDGF ZFP64 YBX1 FEZF1 ZNF121 GATA2 ZNF143 REST TBX21 ZNF518A NUP93 NUDT21 SLC12A3 GC16P056865 MIR138-2
GH16F056869 1 Ensembl ENCODE 0.8 +4.8 4794 0.8 ELF3 ATF1 PKNOX1 CBX3 ARID4B ZNF48 RAD21 RARA ZNF143 CREM HERPUD1 MT1G MT1H SLC12A3 MIR6863
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around SLC12A3 on UCSC Golden Path with GeneCards custom track

Genomic Location for SLC12A3 Gene

Chromosome:
16
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

Genes around SLC12A3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC12A3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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 (PubMed:22406640). Interacts with IL18R1; this interaction is increased by IL18 treatment (By similarity).
    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

Post-translational modifications for SLC12A3 Gene

  • Phosphorylated in response to IL18.
  • 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 Asn 406 and Asn 426
  • Modification sites at PhosphoSitePlus

Other Protein References for SLC12A3 Gene

No data available for DME Specific Peptides for SLC12A3 Gene

Domains & Families 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 :
  • Belongs to the SLC12A transporter family.
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:
Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (PubMed:21613606, PubMed:22009145). Receptor for the proinflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).

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:0015293 symporter activity IEA --
GO:0015377 cation:chloride symporter activity IEA --
GO:0015378 sodium:chloride symporter activity TAS --
genes like me logo Genes that share ontologies with SLC12A3: view
genes like me logo Genes that share phenotypes with SLC12A3: view

Human Phenotype Ontology for SLC12A3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SLC12A3 Gene

MGI Knock Outs for SLC12A3:

Animal Model Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets 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
extracellular 5
plasma membrane 5
cytosol 2

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 IEA,TAS 8670281
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with SLC12A3: view

Pathways & Interactions for SLC12A3 Gene

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

SIGNOR curated interactions for SLC12A3 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for SLC12A3 Gene

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

Drugs & Compounds for SLC12A3 Gene

(21) Drugs for SLC12A3 Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, IUPHAR, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Hydrochlorothiazide Approved, Vet_approved Pharma Inhibition, Inhibitor, blocker, Target, inhibitor 405
Chlorothiazide Approved, Vet_approved Pharma Inhibition, Inhibitor, inhibitor, Target Carbonic anhydrase inhibitor 7
Metolazone Approved Pharma Inhibition, Inhibitor, blocker, Target, inhibitor 14
Bendroflumethiazide Approved Pharma blocker, Target, inhibitor 5
Benzthiazide Approved Pharma inhibitor, Target 0

(5) Additional Compounds for SLC12A3 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
sodium
  • Sodium
  • Sodium ion
7440-23-5
Chloride ion
  • Bertholite
  • Chloor
  • Chlor
  • Chlore
  • Chloride
16887-00-6

(1) ApexBio Compounds for SLC12A3 Gene

Compound Action Cas Number
Bumetanide NKCC cotransporter inhibitor 28395-03-1
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:

Flow Cytometry Products

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 from GTEx, Illumina, BioGPS, and SAGE for SLC12A3 Gene

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

This gene is overexpressed in Kidney - Cortex (x50.4).

Protein differential expression in normal tissues from HIPED for SLC12A3 Gene

This gene is overexpressed in Urine (60.5) and Hair follicle (8.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for SLC12A3 Gene



Protein tissue co-expression partners for SLC12A3 Gene

NURSA nuclear receptor signaling pathways regulating expression of SLC12A3 Gene:

SLC12A3

SOURCE GeneReport for Unigene cluster for SLC12A3 Gene:

Hs.669115

mRNA Expression by UniProt/SwissProt for SLC12A3 Gene:

P55017-S12A3_HUMAN
Tissue specificity: Predominantly expressed in kidney (PubMed:8812482). Not detected in normal aorta, but abundantly expressed in fatty streaks and advanced atherosclerotic lesions (at protein level) (PubMed:26099046).
genes like me logo Genes that share expression patterns with SLC12A3: view

Primer Products

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 34 35
  • 99.42 (n)
dog
(Canis familiaris)
Mammalia SLC12A3 34 35
  • 90.55 (n)
cow
(Bos Taurus)
Mammalia SLC12A3 34 35
  • 90.23 (n)
rat
(Rattus norvegicus)
Mammalia Slc12a3 34
  • 87.49 (n)
mouse
(Mus musculus)
Mammalia Slc12a3 34 16 35
  • 87.08 (n)
oppossum
(Monodelphis domestica)
Mammalia SLC12A3 35
  • 86 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SLC12A3 35
  • 58 (a)
OneToOne
chicken
(Gallus gallus)
Aves SLC12A3 34 35
  • 77.88 (n)
lizard
(Anolis carolinensis)
Reptilia SLC12A3 35
  • 78 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia slc12a3 34
  • 69.77 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.25160 34
zebrafish
(Danio rerio)
Actinopterygii slc12a3 34 35
  • 64.93 (n)
wufj83c03 34
fruit fly
(Drosophila melanogaster)
Insecta CG31547 35
  • 38 (a)
ManyToMany
Ncc69 35
  • 36 (a)
ManyToMany
EG:8D8.3 36
  • 32 (a)
worm
(Caenorhabditis elegans)
Secernentea nkcc-1 35
  • 35 (a)
ManyToMany
B0303.11 35
  • 25 (a)
ManyToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 35
  • 22 (a)
OneToMany
Species where no ortholog for SLC12A3 was found in the sources mined by GeneCards:
  • 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

(6) 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
rs121909379 Gitelman syndrome (GTLMNS) [MIM:263800], other 56,894,558(+) TCTCC(C/T)TGGCC reference, missense
rs121909380 Gitelman syndrome (GTLMNS) [MIM:263800], Gitelman syndrome (GTLMNS) [MIM:263800], Pathogenic 56,886,402(+) CTTCC(A/G/T)CCCGG reference, missense
rs121909382 Gitelman syndrome (GTLMNS) [MIM:263800], Pathogenic 56,884,142(+) GTGGG(A/C/T)GGCCC reference, missense
rs121909383 Gitelman syndrome (GTLMNS) [MIM:263800], Pathogenic 56,872,737(+) CTTCC(C/T)CTCGG reference, missense
rs121909385 Gitelman syndrome (GTLMNS) [MIM:263800], Pathogenic 56,885,307(+) CAACC(C/T)GGCCC reference, missense

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

Variant ID Type Subtype PubMed ID
esv33108 CNV loss 17666407
nsv1059098 CNV gain 25217958
nsv519897 CNV loss 19592680
nsv526264 CNV loss 19592680
nsv977984 CNV duplication 23825009

Variation tolerance for SLC12A3 Gene

Residual Variation Intolerance Score: 16.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.56; 77.94% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SLC12A3 Gene

Human Gene Mutation Database (HGMD)
SLC12A3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SLC12A3

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

Disorders for SLC12A3 Gene

MalaCards: The human disease database

(18) MalaCards diseases for SLC12A3 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
gitelman syndrome
  • hypomagnesemia-hypokalemia, primary renotubular, with hypocalciuria
hypokalemia
  • hypopotassemia
chondrocalcinosis
  • calcium pyrophosphate deposition disease
renal tubular transport disease
  • inborn renal tubular transport disorder
bartter syndrome, type 3
  • bartter disease type 3
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

S12A3_HUMAN
  • Gitelman syndrome (GTLMNS) [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:22009145, 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.

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
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
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 22 25 46 64
  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 22 64
  3. Heterozygous mutations of the sodium chloride cotransporter in Chinese children: prevalence and association with blood pressure. (PMID: 19033254) Hsu Y.J. … Lin S.H. (Nephrol. Dial. Transplant. 2009) 3 22 46 64
  4. [Mutational analysis of a thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in a Japanese population--the Iwaki Health Promotion Project]. (PMID: 19489442) Yasujima M. … Tsutaya S. (Rinsho Byori 2009) 3 22 46 64
  5. Genetic variation at the SLC12A3 locus is unlikely to explain risk for advanced diabetic nephropathy in Caucasians with type 2 diabetes. (PMID: 18263927) Ng D.P. … Krolewski A.S. (Nephrol. Dial. Transplant. 2008) 3 22 46 64

Products for SLC12A3 Gene

Sources for SLC12A3 Gene

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