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Aliases for SLC12A3 Gene

Aliases for SLC12A3 Gene

  • Solute Carrier Family 12 Member 3 2 3
  • Solute Carrier Family 12 (Sodium/Chloride Transporter), Member 3 2 3 5
  • 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 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

Enhancers for SLC12A3 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around SLC12A3 on UCSC Golden Path with GeneCards custom track

Promoters for SLC12A3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs 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.
    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 Asn 406 and Asn 426
  • Modification sites at PhosphoSitePlus

Other Protein References for SLC12A3 Gene

Antibody Products

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

CRISPR Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , 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:0016020 membrane IEA,TAS 8670281
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:0055085 transmembrane transport IEA --
genes like me logo Genes that share ontologies with SLC12A3: view

Drugs & Compounds for SLC12A3 Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Hydrochlorothiazide Approved Pharma Inhibition, Inhibitor, blocker, Target, inhibitor 396
Chlorothiazide 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
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 (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



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 expression patterns with SLC12A3: view

Protein tissue co-expression partners for SLC12A3 Gene

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
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
chimpanzee
(Pan troglodytes)
Mammalia SLC12A3 35
  • 99.42 (n)
  • 99.32 (a)
SLC12A3 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Slc12a3 35
  • 87.49 (n)
  • 91.42 (a)
oppossum
(Monodelphis domestica)
Mammalia SLC12A3 36
  • 86 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SLC12A3 36
  • 58 (a)
OneToOne
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
tropical clawed frog
(Silurana tropicalis)
Amphibia slc12a3 35
  • 69.77 (n)
  • 75.24 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.25160 35
zebrafish
(Danio rerio)
Actinopterygii slc12a3 35
  • 64.93 (n)
  • 65.3 (a)
wufj83c03 35
slc12a3 36
  • 63 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta EG:8D8.3 37
  • 32 (a)
CG31547 36
  • 38 (a)
ManyToMany
Ncc69 36
  • 36 (a)
ManyToMany
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

(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
rs28936388 Gitelman syndrome (GS), Gitelman syndrome (GS) 56,870,119(+) TCTCC(C/T)GGAGT reference, missense
VAR_007114 Gitelman syndrome (GS)
rs28936387 Gitelman syndrome (GS) 56,879,153(+) TGGCC(C/T)GCAGC reference, missense
VAR_007116 Gitelman syndrome (GS)
VAR_007117 Gitelman syndrome (GS)

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

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

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

(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
renal tubular transport disease
  • inborn renal tubular transport disorder
chondrocalcinosis
  • calcium pyrophosphate deposition disease
bartter disease
  • aldosteronism with hyperplasia of the adrenal cortex
- elite association - COSMIC cancer census association via MalaCards

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.

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. 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 67
  2. 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 23 25 26
  3. Molecular pathogenesis of inherited hypertension with hyperkalemia: the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4. (PMID: 12515852) Wilson F.H. … Lifton R.P. (Proc. Natl. Acad. Sci. U.S.A. 2003) 3 23 25 26
  4. The thiazide-sensitive na-cl cotransporter and human disease: reemergence of an old player. (PMID: 12538756) Ellison D.H. (J. Am. Soc. Nephrol. 2003) 23 25 26
  5. Clinical, biochemical and molecular genetic data in five children with Gitelman's syndrome. (PMID: 11456284) Schmidt H. … Kiess W. (Horm. Metab. Res. 2001) 23 25 26

Products for SLC12A3 Gene

Sources for SLC12A3 Gene

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