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Aliases for SLC12A1 Gene

Aliases for SLC12A1 Gene

  • Solute Carrier Family 12 (Sodium/Potassium/Chloride Transporter), Member 1 2 3
  • NKCC2 3 4 6
  • Bumetanide-Sensitive Sodium-(Potassium)-Chloride Cotransporter 2 3 4
  • Kidney-Specific Na-K-Cl Symporter 3 4
  • Solute Carrier Family 12 (Sodium/Potassium/Chloride Transporters), Member 1 3
  • Solute Carrier Family 12 Member 1 3
  • Na-K-2Cl Cotransporter 3
  • NKCC2A Variant A 3
  • BSC1 3

External Ids for SLC12A1 Gene

Summaries for SLC12A1 Gene

Entrez Gene Summary for SLC12A1 Gene

  • This gene encodes a kidney-specific sodium-potassium-chloride cotransporter that is expressed on the luminal membrane of renal epithelial cells of the thick ascending limb of Henle's loop and the macula densa. It plays a key role in concentrating urine and accounts for most of the NaCl resorption. It is sensitive to such diuretics as furosemide and bumetanide. Some Bartter-like syndromes result from defects in this gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity in humans has not been experimentally proven.[provided by RefSeq, May 2010]

GeneCards Summary for SLC12A1 Gene

SLC12A1 (Solute Carrier Family 12 (Sodium/Potassium/Chloride Transporter), Member 1) is a Protein Coding gene. Diseases associated with SLC12A1 include bartter syndrome, type 1 and antenatal bartter syndrome. Among its related pathways are Diuretics Pathway, Pharmacodynamics and Neuropathic Pain-Signaling in Dorsal Horn Neurons. GO annotations related to this gene include sodium:potassium:chloride symporter activity. An important paralog of this gene is SLC12A2.

UniProtKB/Swiss-Prot for SLC12A1 Gene

  • Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume

Tocris Summary for SLC12A1 Gene

  • NKCC cotransporters are membrane-bound channels that play a prominent role in a variety of epithelial absorptive and secretory processes and a direct role in cell volume regulation. There are two NKCC isoforms; NKCC1 and NKCC2. NKCC1 is found on almost all cells types and, importantly, is located on the basolateral membrane of secretory epithelia. In contrast NKCC2 is found exclusively in the kidney, specifically on the apical membrane of absorptive epithelia. The NKCC is distinguished from all other transporters by the fact that it transports Na+, K+ and Cl- stoichiometrically by means of a tightly coupled mechanism that can be blocked by loop diuretics. The NKCC is electrically silent (i.e. not driven by a membrane voltage, nor does it establish one) and requires all three ions to be simultaneously present on the same side of the plasma membrane. This is achieved by an allosteric effect where binding of one ion increases the apparent affinity of the binding site for the other ions. NH4+ may substitute for K+ (especially at NKCC2), which has an important role in NH4+ recycling and excretion of excess acid in the kidney. The NKCC involves a secondary active transport process, despite its requirement for cellular ATPase. It is activated by phosphorylation, which is mediated by PKC and PKA. CK2 binding sites are also present on the NKCC, but the significance is unknown. Protein phosphatases act to reduce NKCC activity by dephosphorylating the transporter. Furthermore, the intracellular concentration of ions, including Cl-, Na+, K+, Mg2+, Ca2+ and H+, has an effect on NKCC activity. There is also evidence that depolymerization of the actin cytoskeleton is associated with NKCC activation.

No data available for Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SLC12A1 Gene

Genomics for SLC12A1 Gene

Genomic Location for SLC12A1 Gene

Start:
48,191,664 bp from pter
End:
48,304,078 bp from pter
Size:
112,415 bases
Orientation:
Plus strand

Genomic View for SLC12A1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SLC12A1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC12A1 Gene

Regulatory Elements for SLC12A1 Gene

Proteins for SLC12A1 Gene

  • Protein details for SLC12A1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13621-S12A1_HUMAN
    Recommended name:
    Solute carrier family 12 member 1
    Protein Accession:
    Q13621
    Secondary Accessions:
    • A8JYA2
    • E9PDW4

    Protein attributes for SLC12A1 Gene

    Size:
    1099 amino acids
    Molecular mass:
    121450 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for SLC12A1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SLC12A1 Gene

Proteomics data for SLC12A1 Gene at MOPED

Post-translational modifications for SLC12A1 Gene

  • Modification sites at PhosphoSitePlus
  • Glycosylation at Asn446 and Asn456

Other Protein References for SLC12A1 Gene

No data available for DME Specific Peptides for SLC12A1 Gene

Domains for SLC12A1 Gene

Gene Families for SLC12A1 Gene

Suggested Antigen Peptide Sequences for SLC12A1 Gene

Graphical View of Domain Structure for InterPro Entry

Q13621

UniProtKB/Swiss-Prot:

S12A1_HUMAN
Family:
  • Belongs to the SLC12A transporter family.:
    • Q13621
genes like me logo Genes that share domains with SLC12A1: view

Function for SLC12A1 Gene

Molecular function for SLC12A1 Gene

GENATLAS Biochemistry: solute carrier family 12 (sodium/potassium/chloride transfer 1,primary mediator of sodium and chloride reabsorption in the apical membrane thick ascending limb of the loop of Henle
UniProtKB/Swiss-Prot EnzymeRegulation: Activated by WNK3.
UniProtKB/Swiss-Prot Function: Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume

Gene Ontology (GO) - Molecular Function for SLC12A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005215 transporter activity --
GO:0005515 protein binding --
GO:0008511 sodium:potassium:chloride symporter activity TAS 8640224
GO:0015377 cation:chloride symporter activity --
genes like me logo Genes that share ontologies with SLC12A1: view
genes like me logo Genes that share phenotypes with SLC12A1: view

Animal Models for SLC12A1 Gene

MGI Knock Outs for SLC12A1:

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targeting and HOMER Transcription for SLC12A1 Gene

Localization for SLC12A1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC12A1 Gene

Membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SLC12A1 Gene COMPARTMENTS Subcellular localization image for SLC12A1 gene
Compartment Confidence
plasma membrane 4
cytosol 2
nucleus 2
extracellular 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for SLC12A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0016020 membrane TAS 7929272
GO:0016021 integral component of membrane IEA --
GO:0016324 apical plasma membrane IEA --
GO:0070062 extracellular exosome IDA 15326289
genes like me logo Genes that share ontologies with SLC12A1: view

Pathways for SLC12A1 Gene

genes like me logo Genes that share pathways with SLC12A1: view

Gene Ontology (GO) - Biological Process for SLC12A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001822 kidney development IEA --
GO:0006810 transport TAS 8640224
GO:0006811 ion transport TAS --
GO:0006813 potassium ion transport IEA --
GO:0006814 sodium ion transport IEA --
genes like me logo Genes that share ontologies with SLC12A1: view

Compounds for SLC12A1 Gene

(2) Tocris Compounds for SLC12A1 Gene

Compound Action Cas Number
Bumetanide Na+/2Cl-/K+ (NKCC) cotransporter inhibitor [28395-03-1]
Furosemide Na+/2Cl-/K+ (NKCC) cotransporter inhibitor. Also antagonizes GABAA [54-31-9]

(3) HMDB Compounds for SLC12A1 Gene

Compound Synonyms Cas Number PubMed IDs
Chlorine
  • Cl2
16887-00-6
Furosemide
  • Acetic acid potassium salt
54-31-9
Sodium
  • Sodium
7440-23-5

(13) Drugbank Compounds for SLC12A1 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Bumetanide
  • Bumetanida [INN-Spanish]
28395-03-1 target inhibitor
Chlormerodrin
62-37-3 target inducer
Chlorthalidone
  • Chlorothalidone
77-36-1 target inhibitor
Ethacrynic acid
  • Etacrinic acid
58-54-8 target inhibitor
Furosemide
  • Dihydroflumethiazide
54-31-9 target inhibitor

(3) IUPHAR Ligand for SLC12A1 Gene

Ligand Type Action Affinity Pubmed IDs
bumetanide Inhibitor Inhibition
piretanide Inhibitor Inhibition
furosemide Inhibitor Inhibition

(16) Novoseek inferred chemical compound relationships for SLC12A1 Gene

Compound -log(P) Hits PubMed IDs
bumetanide 81.5 9
chloride 70 11
nacl 62.4 7
86rb 60.3 1
potassium 57.7 22
genes like me logo Genes that share compounds with SLC12A1: view

Transcripts for SLC12A1 Gene

Unigene Clusters for SLC12A1 Gene

Solute carrier family 12 (sodium/potassium/chloride transporters), member 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SLC12A1 Gene

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

ExUns: 24 ^ 25 ^ 26
SP1:
SP2:
SP3:

Relevant External Links for SLC12A1 Gene

GeneLoc Exon Structure for
SLC12A1
ECgene alternative splicing isoforms for
SLC12A1

Expression for SLC12A1 Gene

mRNA expression in normal human tissues for SLC12A1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SLC12A1 Gene

This gene is overexpressed in Kidney - Cortex (47.8).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for SLC12A1 Gene

SOURCE GeneReport for Unigene cluster for SLC12A1 Gene Hs.123116

mRNA Expression by UniProt/SwissProt for SLC12A1 Gene

Q13621-S12A1_HUMAN
Tissue specificity: Kidney specific
genes like me logo Genes that share expressions with SLC12A1: view

Orthologs for SLC12A1 Gene

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

Orthologs for SLC12A1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SLC12A1 35
  • 99.55 (n)
  • 99.45 (a)
SLC12A1 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SLC12A1 35
  • 92.02 (n)
  • 94.45 (a)
SLC12A1 36
  • 93 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SLC12A1 35
  • 92.24 (n)
  • 95.36 (a)
SLC12A1 36
  • 95 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Slc12a1 35
  • 88.77 (n)
  • 94.34 (a)
Slc12a1 16
Slc12a1 36
  • 93 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SLC12A1 36
  • 93 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SLC12A1 36
  • 71 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Slc12a1 35
  • 87.88 (n)
  • 93.97 (a)
chicken
(Gallus gallus)
Aves SLC12A1 35
  • 79.52 (n)
  • 83.64 (a)
SLC12A1 36
  • 83 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 36
  • 81 (a)
OneToMany
-- 36
  • 79 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia slc12a1 35
  • 74.68 (n)
  • 78.45 (a)
Str.12192 35
zebrafish
(Danio rerio)
Actinopterygii slc12a1 36
  • 67 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG31547 36
  • 41 (a)
ManyToMany
Ncc69 36
  • 42 (a)
ManyToMany
CG4357 37
  • 47 (a)
EG:8D8.3 37
  • 32 (a)
worm
(Caenorhabditis elegans)
Secernentea B0303.11 36
  • 27 (a)
ManyToMany
nkcc-1 35
  • 53.3 (n)
  • 48.19 (a)
nkcc-1 36
  • 39 (a)
ManyToMany
F10E7.9 37
  • 25 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 36
  • 21 (a)
OneToMany
Species with no ortholog for SLC12A1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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 SLC12A1 Gene

ENSEMBL:
Gene Tree for SLC12A1 (if available)
TreeFam:
Gene Tree for SLC12A1 (if available)

Paralogs for SLC12A1 Gene

Paralogs for SLC12A1 Gene

Selected SIMAP similar genes for SLC12A1 Gene using alignment to 8 proteins:

genes like me logo Genes that share paralogs with SLC12A1: view

Variants for SLC12A1 Gene

Sequence variations from dbSNP and Humsavar for SLC12A1 Gene

SNP ID Clin Chr 15 pos Sequence Context AA Info Type MAF
rs938504 -- 48,212,883(+) TAATT(C/T)GTAAA intron-variant
rs1224427 -- 48,278,911(-) TTTGA(A/G)AAATA intron-variant
rs1224428 -- 48,278,201(-) agtgg(C/T)gcgat intron-variant
rs1224429 -- 48,277,956(-) CATAG(A/G)ATGCA intron-variant
rs1224430 -- 48,273,274(-) attga(A/G)aaagg intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SLC12A1 Gene

Variant ID Type Subtype PubMed ID
dgv746e1 CNV Complex 17122850
nsv526690 CNV Loss 19592680
nsv522923 CNV Loss 19592680
nsv904203 CNV Gain 21882294
esv2474615 CNV Deletion 19546169
esv2749657 CNV Deletion 23290073
esv2617587 CNV Deletion 19546169
esv7684 CNV Loss 19470904
esv2666859 CNV Deletion 23128226

Relevant External Links for SLC12A1 Gene

HapMap Linkage Disequilibrium report
SLC12A1
Human Gene Mutation Database (HGMD)
SLC12A1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLC12A1 Gene

Disorders for SLC12A1 Gene

(1) OMIM Diseases for SLC12A1 Gene (600839)

UniProtKB/Swiss-Prot

S12A1_HUMAN
  • Bartter syndrome 1 (BS1) [MIM:601678]: An autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. Bartter syndrome type 1 is a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia. {ECO:0000269 PubMed:8640224}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(19) Novoseek inferred disease relationships for SLC12A1 Gene

Disease -log(P) Hits PubMed IDs
bartters syndrome 95.9 32
bartter syndrome, classic 94 2
gitelman syndrome 91.4 4
hyperprostaglandin e syndrome 91.3 2
metabolic alkalosis 85.1 2

Genatlas disease for SLC12A1 Gene

Bartter syndrome,hypokalemic,hypochloremic metabolic alkalosis with hyperkaliury,hyperexcretion of prostaglandin E,hyperreninemia hyperaldosteronism with normal blood pressure,insensitivity to AGT2,and hyperplasia of juxtaglomerular apparatus,autosomal recessive,presenting as an antenatal form with hydramnios prematurity and dehydration at built and a classic form with failure to thrive

Relevant External Links for SLC12A1

Genetic Association Database (GAD)
SLC12A1
Human Genome Epidemiology (HuGE) Navigator
SLC12A1
genes like me logo Genes that share disorders with SLC12A1: view

Publications for SLC12A1 Gene

  1. Bartter's syndrome, hypokalemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. (PMID: 8640224) Simon D.B. … Lifton R.P. (Nat. Genet. 1996) 2 3 4 23
  2. Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. (PMID: 17460608) Vormfelde S.V. … BrockmAPller J. (Clin. Pharmacol. Ther. 2007) 3 23 25 48
  3. Interaction of alpha(1)-Na,K-ATPase and Na,K,2Cl-cotransporter genes in human essential hypertension. (PMID: 11509477) Glorioso N. … Ruiz-Opazo N. (Hypertension 2001) 3 23 48
  4. Non-association of the thiazide-sensitive Na,Cl-cotransporter gene with polygenic hypertension in both rats and humans. (PMID: 11564973) Song Y. … Ruiz-Opazo N. (J. Hypertens. 2001) 3 23 48
  5. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. (PMID: 18391953) Ji W. … Lifton R.P. (Nat. Genet. 2008) 3 23 48

Products for SLC12A1 Gene

Sources for SLC12A1 Gene

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