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Symbol SLC9A3 contributors: mct/pgu - updated : 11-10-2018
HGNC name solute carrier family 9 (sodium/hydrogen exchanger), isoform 3
HGNC id 11073
Corresponding disease
DIAR8 diarrhea 8, secretory sodium, congenital
Location 5p15.33      Physical location : 473.333 - 524.549
Synonym symbol(s) APNH3, NHE3, SLC9A3B, MGC126718, MGC126720
TYPE functioning gene
STRUCTURE 52.45 kb     17 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site   transcription factor
text structure Sp1 and Sp3 acting as positive regulators of the SLC9A3 expression
MAPPING cloned Y linked Y status confirmed
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
17 - 2777 - 834 - 2015 26377793
17 - 3983 - 825 - 2015 26377793
Type restricted
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestine   predominantly Homo sapiens
Reproductivemale systemmale genital tractepididymis   Homo sapiens
 male systemmale genital tractvas deferens   Homo sapiens
Respiratoryrespiratory tracttrachea   
Urinarykidneytubuleconvoluted tubuleproximal tubule  Homo sapiens
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
SystemCellPubmedSpeciesStageRna symbol
Digestiveepithelial cell Homo sapiens
cell lineage
cell lines
physiological period perinatal, growth/childhood
Text maturational increase in postnatal brush-border membrane (BBM) vesicle SLC9A3 protein abundance and decrease in SLC9A8 protein abundance
  • ten (? twelve) transmembrane segments protein
  • a large acidic cytoplasmic C terminal domain
    FAMILY solute carrier protein family 9,sodium/hydrogen exchange
    CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
  • expressed on the apical membrane of intestinal epithelial cells
  • basic FUNCTION
  • involved in intracellular pH regulation and cell volume
  • playing an essential role for Na+ absorption in the ileum and is expressed in a cell-specific manner in the apical membrane of the intestinal epithelial cells
  • having a role in the maintenance of acid-base balance
  • plays an important role in neutral Na(+) transport in mammalian epithelial cells
  • modulatory effect of the SLC9A3 gene on susceptibility to infections and pulmonary function in children with cystic fibrosis
  • role of SLC9A3 in the acidification of the male reproductive tract and its requirement for male fertility
  • is responsible for the bulk of salt reabsorption in the proximal tubule, and its activity may be affected the most by the increase in length of this renal segment
  • plays an important role in fluid and bicarbonate reabsorption in the proximal convoluted tubule but does not play an important role in NH4 excretion
  • partially associate with lipid rafts in the native brush border membrane (BBM), and SLC9A3 raft association had an impact on SLC9A3 transport activity and regulation
  • is located in chemosensitive areas of the medulla oblongata and plays an important role in the central control of respiration
  • can act as a direction sensor for cells and SLC9A3 phosphorylation in persistent directional cell migration does not involve PI3K/AKT1 during electrotaxis
  • located in the apical dense microvilli (brush border), and plays a major role in the reabsorption of NaCl and water in the renal proximal tubule
  • may play a role in the pathogenesis of cholesterol gallstone disease (CGD)
  • is a major route of sodium absorption in the intestine and kidney 0)
  • renal SLC9A3 is required to maintain blood pressure and steady-state plasma sodium levels when dietary sodium chloride intake is modified
  • Na&
  • 8314;/H&
    8314; exchanger, regulating the transepithelial absorption of Na&
    8314; and water
  • has a vital role in acrosomal formation during spermiogenesis
    a component SLC9A3, SHANK2, and ARHGEF7 form a macromolecular complex when expressed heterologously in mammalian cells
    small molecule
  • interacting with SHANK2 (novel interacting protein that is involved in the fine regulation of transepithelial salt and water transport through affecting SLC9A3 expression and activity)
  • interacting with PDZK1 (reconstitutes calcium inhibition of SLC9A3 activity by anchoring SLC9A3 basally and releasing it with elevated Ca(2+))
  • SYT1 plays an important role in cAMP-stimulated endocytosis of apical SLC9A3 through cAMP-dependent phosphorylation of S605 that is required for NHE3 and SYT1 association
  • AHCYL1 is critically involved in mediating activation of SLC9A3 by AGT via a Ca(2+)/calmodulin-dependent protein kinases II-dependent pathway
  • SGK2 may play a previously unrecognized role in the control of transtubular Na(+) transport through SLC9A3 in the proximal tubule
  • cAMP-dependent inhibition of SLC9A3 activity requires either SLC9A3R1 or SLC9A3R2
  • role for SLC9A1 in the long-term regulation of renal tubule function, suggesting that the regulatory interaction whereby SLC9A1 enhances the activity of SLC9A3 in the medullary thick ascending limb and plays a role in the chronic regulation of HCO(3)(-) absorption
  • SGK3 is a novel endosomal kinase that acutely regulates SLC9A3 in a PI3K-dependent mechanism
  • AHCYL1 plays an important role in pHi regulation, mediated by SLC9A3, and further regulated by STK39
  • MYO6 is required for basal and stimulated endocytosis of SLC9A3 in intestinal cells, suggesting that MYO6 also moves SLC9A3 down the microvillus
  • role for PER1 in the transcriptional regulation of SLC9A3 and SLC5A1 in the kidney
  • SLC9A3 interacts with CFTR in the pancreatic duct and functions as a genetic modifier of CF
  • interdependence between SLC9A3 and CFTR is critical for maintaining a precise microenvironment in the epithelial cytoarchitecture of the male reproductive tract
  • direct interaction of MLXIPL with the SLC2A5 promoter, but not the SLC9A3 promoter, in the small intestine
  • cell & other
    Phosphorylated by RPS6KA3 (RPS6KA3 is a new kinase that regulates SLC9A3 activity by direct phosphorylation)
    Other transcriptional regulation by serotonin in intestinal epithelial cells
    regulated by glucocorticoids (have been found to regulate SLC9A3 function in the intestine)
    regulated by thyroid hormone (plays a potential role in the developmental isoform change from SLC9A8 to SLC9A3 and decreases SLC9A8 activity
    corresponding disease(s) DIAR8
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in Barrett esophagus
    tumoral   amplification    
    in early stages of non-small cell lung cancer
    constitutional     --low  
    in patients with ulcerative colitis
  • to the sudden infant death syndrome (SIDS)
  • to preeclampsia
  • Variant & Polymorphism other
  • the level of SLC9A3 expression in brainstem tissue may contribute to the vulnerability of infants for SIDS
  • Rs4957061 in SLC9A3 was significantly associated with a reduced risk of preeclampsia in whites
  • Candidate gene
    Therapy target
  • depleted Slc9a3 in male mice causes infertility due to the abnormal dilated lumen of the rete testis and efferent ductules
  • Cftr expression was dramatically decreased in the epididymis and vas deferens of Slc9a3 knockout mice