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Aliases for SLC12A1 Gene

Aliases for SLC12A1 Gene

  • Solute Carrier Family 12 Member 1 2 3 5
  • Solute Carrier Family 12 (Sodium/Potassium/Chloride Transporter), Member 1 2 3
  • Bumetanide-Sensitive Sodium-(Potassium)-Chloride Cotransporter 2 3 4
  • Kidney-Specific Na-K-Cl Symporter 3 4
  • NKCC2 3 4
  • Solute Carrier Family 12 (Sodium/Potassium/Chloride Transporters), Member 1 3
  • Na-K-2Cl Cotransporter 3
  • NKCC2A Variant A 3
  • BSC1 3

External Ids for SLC12A1 Gene

Previous GeneCards Identifiers for SLC12A1 Gene

  • GC15P044057
  • GC15P041545
  • GC15P046078
  • GC15P046214
  • GC15P046215
  • GC15P046287
  • GC15P048498
  • GC15P025334

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 Member 1) is a Protein Coding gene. Diseases associated with SLC12A1 include Bartter Syndrome, Type 1, Antenatal and Antenatal Bartter Syndrome. Among its related pathways are Neuropathic Pain-Signaling in Dorsal Horn Neurons and Diuretics Pathway, Pharmacodynamics. Gene Ontology (GO) annotations related to this gene include transporter activity and 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

  • Na+/K+/Cl- Symporters (NKCC) are membrane-bound channels that play a major role in a variety of epithelial absorptive and secretory processes and a direct role in cell volume regulation and possibly in cell cycle regulation. There are two NKCC isoforms: NKCC1 and NKCC2.

Additional gene information for SLC12A1 Gene

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

Genomics for SLC12A1 Gene

GeneHancer (GH) Regulatory Elements for SLC12A1 Gene

Promoters and enhancers for SLC12A1 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH15I048190 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE 550.8 -0.2 -186 1 ELF3 MXI1 ZNF792 SAP130 MAX MZF1 SIN3A DNMT3B ZSCAN9 RARA PIR31092 SLC12A1 LOC105370807 CTXN2
GH15I048206 Promoter 0.5 EPDnew 550.4 +14.6 14619 0.1 SLC12A1 SLC24A5 ENSG00000259385 GC15P048230 GC15P048225
GH15I048330 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 57.9 +140.3 140337 3.8 HDGF FOXA2 ZFP64 ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 POLR2B DUT ENSG00000259488 SLC12A1 LOC105370807 CEP152 FBN1 GC15P048420
GH15I048285 Enhancer 0.9 Ensembl ENCODE 43.6 +94.2 94236 0.6 ELF3 CTCF ZNF654 TRIM22 REST BMI1 ZNF2 ZBTB40 RAD21 PRDM6 SLC12A1 ENSG00000202542 DUT PIR60543 GC15M048328
GH15I048297 Enhancer 0.4 ENCODE dbSUPER 43.5 +106.2 106155 0.2 SLC12A1 GC15M048328 ENSG00000202542 PIR60543
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around SLC12A1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SLC12A1 gene promoter:

Genomic Locations for SLC12A1 Gene

Genomic Locations for SLC12A1 Gene
112,415 bases
Plus strand

Genomic View for SLC12A1 Gene

Genes around SLC12A1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC12A1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLC12A1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC12A1 Gene

Proteins for SLC12A1 Gene

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

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

    Protein attributes for SLC12A1 Gene

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

    Alternative splice isoforms for SLC12A1 Gene


neXtProt entry for SLC12A1 Gene

Post-translational modifications for SLC12A1 Gene

  • Glycosylation at posLast=446446 and posLast=456456
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for SLC12A1 Gene

Domains & Families for SLC12A1 Gene

Gene Families for SLC12A1 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • FDA approved drug targets
  • Predicted membrane proteins
  • Transporters

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the SLC12A transporter family.
  • Belongs to the SLC12A transporter family.
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.

Phenotypes From GWAS Catalog for SLC12A1 Gene

Gene Ontology (GO) - Molecular Function for SLC12A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008511 sodium:potassium:chloride symporter activity TAS --
GO:0015293 symporter activity IEA --
GO:0015377 cation:chloride symporter activity IEA --
genes like me logo Genes that share ontologies with SLC12A1: view
genes like me logo Genes that share phenotypes with SLC12A1: view

Human Phenotype Ontology for SLC12A1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SLC12A1 Gene

MGI Knock Outs for SLC12A1:

Animal Model Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targets 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

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SLC12A1 gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 2
cytosol 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Vesicles (2)
  • Nucleus (1)
See all subcellular structures

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 IBA --
GO:0070062 extracellular exosome IDA 15326289
genes like me logo Genes that share ontologies with SLC12A1: view

Pathways & Interactions for SLC12A1 Gene

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

Pathways by source for SLC12A1 Gene

Gene Ontology (GO) - Biological Process for SLC12A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport TAS 8640224
GO:0006811 ion transport TAS --
GO:0006813 potassium ion transport IEA --
GO:0006814 sodium ion transport IEA --
GO:0034220 ion transmembrane transport ISS --
genes like me logo Genes that share ontologies with SLC12A1: view

No data available for SIGNOR curated interactions for SLC12A1 Gene

Drugs & Compounds for SLC12A1 Gene

(20) Drugs for SLC12A1 Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Bumetanide Approved Pharma Agonist, Target, inhibitor, blocker NKCC cotransporter inhibitor, Na+/2Cl-/K+ (NKCC) symporter inhibitor 19
Furosemide Approved, Vet_approved Pharma Agonist, Target, inhibitor, blocker GABAA receptors antagonist, Na+/2Cl-/K+ (NKCC) symporter inhibitor. Also antagonizes GABAA 209
Chlormerodrin Approved, Withdrawn Pharma Target, inducer, inhibitor 0
Chlorthalidone Approved Pharma Target, inhibitor, blocker 66
Ethacrynic acid Approved, Investigational Pharma Target, inhibitor, blocker 3

(8) Additional Compounds for SLC12A1 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • Sodium
  • Sodium ion
Chloride ion
  • Bertholite
  • Chloor
  • Chlor
  • Chlore
  • Chloride

(2) Tocris Compounds for SLC12A1 Gene

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

(2) ApexBio Compounds for SLC12A1 Gene

Compound Action Cas Number
Bumetanide NKCC cotransporter inhibitor 28395-03-1
Furosemide GABAA receptors antagonist 54-31-9
genes like me logo Genes that share compounds with SLC12A1: view

Drug Products

Transcripts for SLC12A1 Gene

Unigene Clusters for SLC12A1 Gene

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

Clone Products

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: -
SP3: - - -

ExUns: 24 ^ 25 ^ 26

Relevant External Links for SLC12A1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for SLC12A1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE 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 (x47.8).

Protein differential expression in normal tissues from HIPED for SLC12A1 Gene

This gene is overexpressed in Urine (59.0) and Serum (8.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for SLC12A1 Gene

Protein tissue co-expression partners for SLC12A1 Gene

NURSA nuclear receptor signaling pathways regulating expression of SLC12A1 Gene:


SOURCE GeneReport for Unigene cluster for SLC12A1 Gene:


mRNA Expression by UniProt/SwissProt for SLC12A1 Gene:

Tissue specificity: Kidney specific.

Evidence on tissue expression from TISSUES for SLC12A1 Gene

  • Kidney(4.8)
  • Nervous system(4.3)
  • Blood(3.1)
  • Urine(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SLC12A1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • skeletal muscle
  • skeleton
  • urinary
Head and neck:
  • brain
  • cheek
  • chin
  • ear
  • eye
  • face
  • forehead
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • outer ear
  • parathyroid
  • pituitary gland
  • skull
  • thyroid
  • chest wall
  • clavicle
  • esophagus
  • heart
  • rib
  • rib cage
  • scapula
  • sternum
  • adrenal gland
  • duodenum
  • intestine
  • kidney
  • large intestine
  • pancreas
  • small intestine
  • stomach
  • pelvis
  • placenta
  • prostate
  • rectum
  • ureter
  • uterus
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
  • blood
  • blood vessel
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns 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
(Pan troglodytes)
Mammalia SLC12A1 33 34
  • 99.55 (n)
(Monodelphis domestica)
Mammalia SLC12A1 34
  • 93 (a)
(Canis familiaris)
Mammalia SLC12A1 33 34
  • 92.24 (n)
(Bos Taurus)
Mammalia SLC12A1 33 34
  • 92.02 (n)
(Mus musculus)
Mammalia Slc12a1 33 16 34
  • 88.77 (n)
(Rattus norvegicus)
Mammalia Slc12a1 33
  • 87.88 (n)
(Ornithorhynchus anatinus)
Mammalia SLC12A1 34
  • 71 (a)
(Gallus gallus)
Aves SLC12A1 33 34
  • 79.52 (n)
(Anolis carolinensis)
Reptilia -- 34
  • 81 (a)
-- 34
  • 79 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia slc12a1 33
  • 74.68 (n)
Str.12192 33
(Danio rerio)
Actinopterygii slc12a1 34
  • 67 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG4357 35
  • 47 (a)
Ncc69 34
  • 42 (a)
CG31547 34
  • 41 (a)
EG:8D8.3 35
  • 32 (a)
(Caenorhabditis elegans)
Secernentea nkcc-1 33 34
  • 53.3 (n)
B0303.11 34
  • 27 (a)
F10E7.9 35
  • 25 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 34
  • 21 (a)
Species where no ortholog for SLC12A1 was found in the sources mined by GeneCards:
  • 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

Gene Tree for SLC12A1 (if available)
Gene Tree for SLC12A1 (if available)

Paralogs for SLC12A1 Gene

Paralogs for SLC12A1 Gene

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 Variation AA Info Type
rs1018912667 uncertain-significance, Antenatal Bartter Syndrome 48,207,620(+) C/T 5_prime_UTR_variant
rs1057519608 pathogenic, Bartter syndrome, type 1, antenatal 48,259,251(+) GG/G coding_sequence_variant, frameshift
rs1057520300 pathogenic, Bartter syndrome, type 1, antenatal 48,234,926(+) C/ coding_sequence_variant, frameshift
rs1057520301 pathogenic, Bartter syndrome, type 1, antenatal 48,251,711(+) C/A/G coding_sequence_variant, missense_variant
rs1057520302 pathogenic, Bartter syndrome, type 1, antenatal 48,288,430(+) C/CC coding_sequence_variant, frameshift

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

Variant ID Type Subtype PubMed ID
esv2474615 CNV deletion 19546169
esv2617587 CNV deletion 19546169
esv2666859 CNV deletion 23128226
esv2749657 CNV deletion 23290073
esv2760030 CNV loss 17122850
esv3552414 CNV deletion 23714750
esv3892690 CNV loss 25118596
esv7684 CNV loss 19470904
nsv1131183 CNV deletion 24896259
nsv1138367 CNV deletion 24896259
nsv1153682 CNV deletion 26484159
nsv522923 CNV loss 19592680
nsv526690 CNV loss 19592680
nsv957972 CNV deletion 24416366

Variation tolerance for SLC12A1 Gene

Residual Variation Intolerance Score: 50.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.60; 65.35% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SLC12A1 Gene

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

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

Disorders for SLC12A1 Gene

MalaCards: The human disease database

(18) MalaCards diseases for SLC12A1 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
bartter syndrome, type 1, antenatal
  • barts1
antenatal bartter syndrome
  • bartter syndrome, furosemide type
gitelman syndrome
  • gtlmns
  • hypercalcemic nephropathy
  • hypopotassemia
- elite association - COSMIC cancer census association via MalaCards


  • Bartter syndrome 1, antenatal (BARTS1) [MIM:601678]: A form of Bartter syndrome, 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. BARTS1 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.

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

Additional Disease Information for SLC12A1

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with SLC12A1: view

Publications for SLC12A1 Gene

  1. Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. (PMID: 17460608) Vormfelde SV … Brockmöller J (Clinical pharmacology and therapeutics 2007) 3 22 25 44 58
  2. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. (PMID: 18391953) Ji W … Lifton RP (Nature genetics 2008) 3 22 44 58
  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 (Dallas, Tex. : 1979) 2001) 3 22 44 58
  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 (Journal of hypertension 2001) 3 22 44 58
  5. Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. (PMID: 8640224) Simon DB … Lifton RP (Nature genetics 1996) 2 3 4 58

Products for SLC12A1 Gene

Sources for SLC12A1 Gene

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