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Symbol SLC8A1 contributors: mct/npt/pgu - updated : 23-03-2016
HGNC name solute carrier family 8 (sodium/calcium exchanger), member 1
HGNC id 11068
Location 2p22.1      Physical location : 40.339.286 - 40.739.575
Synonym name
  • sodium/calcium exchanger 1
  • Na+/Ca++ exchanger
  • Na(+)/Ca(2+)-exchange protein 1
  • Synonym symbol(s) NCX1, CNC, MGC119581, DKFZp779F0871, FLJ37694, FLJ43417, NCX
    TYPE functioning gene
    SPECIAL FEATURE overlapping
    STRUCTURE 400.30 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure an anusual 1.8kb exon
    MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 6053 108.4 973 - 2001 11241183
    NaCa1 or NCX1.1, isoform A
    9 - 6038 107.8 968 - 2001 11241183
    8 - 6014 - 960 - 2001 11241183
  • NaCa7 or NCX1.7 isoform C
  • 8 - 6032 104.6 937 - 2001 11241183
    NaCa3, NCX1.3 isoform D
    - - 6029 - 965 - -
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Nervousnervespinal nerve  highly Homo sapiensAdult
    Urinarykidney   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
    physiological period fetal
    Text heart
  • N-terminal domain with the first five transmembrane segments (residues 1-217)
  • a large intracellular cytoplasmic loop (residues 218-764), which contains two structurally homologous Ca2+ binding domains CBD1 and CBD2
  • a C-terminal domain comprising the last four transmembrane segments (residues 765-93)
  • eleven transmembrane segments (11TM) protein
  • four Ca2+ sites in CBD1 and two Ca2+ sites in CBD2 domains , and CBD2 is known to bind two Ca(2+) ions using its Ca(2+)-binding sites I and II, and also binds Mg(2+) at both sites, but with significantly different affinities
  • conjugated GlycoP
  • sodium/potassium/calcium exchanger family, CaCA (Ca(2+)/Cation Antiporter) superfamily
  • SLC8 subfamily
  • NCX gene family
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
  • sarcolemma
  • co-localized with APP in synaptic terminals
  • basic FUNCTION
  • rapid transport of Ca2+ during excitation contraction, preventing overloading of intracellular stores during relaxation
  • involved in the regulation of osteoclasts cytosolic calcium and bone resorption
  • involved in the contractile regulation of small arteries and in the development of salt-dependent hypertension, through calcium entry
  • intimately involved in the regulation of calcium (Ca(2+)) homeostasis in many tissues including excitation-secretion coupling in pancreatic beta-cells
  • play a crucial role in ionic regulation because they are the major bidirectional system promoting the efflux and influx of Na(+) and Ca(2+) ions
  • with SLC8A3, represent novel additional molecular targets for the prosurvival action of PI3-K/Akt pathway
  • involvement in the directional Ca(2+) extrusion pathway from cells to the enamel mineralizing front
  • new physiological role for mitochondrial as the key player in glutamate-induced energy production
  • extrudes calcium from cardiac myocytes during relaxation and returns the myocardium to its resting state after excitation
  • is also the major pathway for Na+ influx into mitochondria
  • can directly act as a regulator of "activity-dependent signal transduction" mediating changes in its own expression
  • SLC8A1 and SLC8A3, but not SLC8A2, were divergently modulated during oligodendrocyte precursor cells differentiation into oligodendrocyte
  • key component of certain distinct signaling pathways that activate vascular smooth muscle contraction in response to stretch (i.e., myogenic response) and to activation of certain G-protein-coupled receptors
  • plays a major role in the cardiac contractile cycle via efflux of Ca2+ from the cardiomyocyte after its transient rise during systole
  • contribute to excitation-contraction coupling, long-term potentiation of the brain and learning, blood pressure regulation, immune response, neurotransmitter and insulin secretion
  • Na(+)/Ca(2+) exchanger-mediated Ca(2+) clearance mediated by SLC8B1 and SLC8A1 is crucial for optimizing mitochondrial function, which in turn contributes to vesicle recruitment for sustained exocytosis in pancreatic beta-cells
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS active transport
    a component
    small molecule nucleotide,
  • ATP dependent
  • ions Ca2+ binding
  • interacted with FXYD1 through the intracellular loop most likely at residues 218-358
  • sorcin binding to the SLC8A1 calcium binding domains (CBD1)
  • protein
  • physical interaction between SLC1A1 and SLC8A1 both in neuronal and glial mitochondria, and SLC8A1 is an essential modulator of this glutamate transporter
  • DPYSL2 interacts with NMDAR and SLC8A1 and regulates their functional activity
  • presynaptic control of SLC6A5 by physical and functional association with plasma membrane Ca2+-ATPase SLC8A1 and ATP2B1
  • SLC8A1 requires ANO6 to efficiently translocate Ca(2+) out of osteoblasts into the calcifying bone matrix
  • coupling between TRPC3 and the SLC8A1 transporter contributed to VEGFA-induced ERK1/2 activation and angiogenesis in primary endothelial cells
  • cell & other
    Other role of cytosolic Na+ as a dynamic and important regulator of the mitochondrial SLC8A1
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in hypertrophy and is often found elevated in end-stage heart failure
    constitutional     --over  
    co-localized with APP in synaptic terminals and with SLC8A2, SLC8A3, are up-regulated in nerve terminals containing APP, in cerebral cortex affected by Alzheimer disease
    Susceptibility to prolongation of the electrocardiographic QT interval
    Variant & Polymorphism SNP
  • association between a SNP, rs13017846 with prolongation of the electrocardiographic QT interval
  • Candidate gene
    Therapy target
    potential therapeutic targets for reducing the bystander damage that often results from microglia activation in the damaged CNS
  • severe circulation defects and defective placentation in homozygous Ncx1(N87K4) mutant embryos