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Solute carrier family 4 (sodium bicarbonate cotransporter), member 4
Symbols SLC4A4 ; HNBC1; KNBC; NBC1; NBC2; NBCe1-A; SLC4A5; hhNMC; pNBC
External IDs OMIM603345 MGI1927555 HomoloGene55776 GeneCards: SLC4A4 Gene
RNA expression pattern
PBB GE SLC4A4 203908 at tn.png
PBB GE SLC4A4 210738 s at tn.png
PBB GE SLC4A4 210739 x at tn.png
More reference expression data
Species Human Mouse
Entrez 8671 54403
Ensembl ENSG00000080493 ENSMUSG00000060961
UniProt Q9Y6R1 O88343
RefSeq (mRNA) NM_001098484 NM_001136260
RefSeq (protein) NP_001091954 NP_001129732
Location (UCSC) Chr 4:
71.19 – 71.57 Mb
Chr 5:
88.89 – 89.24 Mb
PubMed search [1] [2]

Electrogenic sodium bicarbonate cotransporter 1 is a membrane transport protein that in humans is encoded by the SLC4A4 gene.[1][2][3]


Sodium bicarbonate cotransporters (NBCs) mediate the coupled movement of sodium and bicarbonate ions across the plasma membrane of many cells. This is an electrogenic process with an apparent stoichiometry of 3 bicarbonate ions per sodium ion. Sodium bicarbonate cotransport is involved in bicarbonate secretion/absorption and intracellular pH regulation. Romero and Boron (1999) reviewed NBCs. Soleimani and Burnham (2000) reviewed NBCs and their regulation in physiologic and pathophysiologic states.[supplied by OMIM][3]

Clinical significance[edit]

NBCe1 may participate in regulation of brain extracellular space pH. Some mutations in NBCe1 have been associated with Familial hemiplegic migraine.[4] Other NBCe1 mutations disrupt kidney bicarbonate transport and cause proximal renal tubular acidosis.[5]

Splice variants[edit]

NBCe1-A aka kNBC1 (mainly expressed in the kidney)

NBCe1-B aka pNBC1 (expressed in the pancreas and elsewhere)

NBCe1-C (expressed in the brain)


The renal SLC4A4 gene product NBCe1-A is specifically expressed in the basolateral membranes of proximal tubule epithelia.

See also[edit]


  1. ^ Burnham CE, Amlal H, Wang Z, Shull GE, Soleimani M (Aug 1997). "Cloning and functional expression of a human kidney Na+:HCO3- cotransporter". J Biol Chem 272 (31): 19111–4. doi:10.1074/jbc.272.31.19111. PMID 9235899. 
  2. ^ Abuladze N, Lee I, Newman D, Hwang J, Boorer K, Pushkin A, Kurtz I (Aug 1998). "Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter". J Biol Chem 273 (28): 17689–95. doi:10.1074/jbc.273.28.17689. PMID 9651366. 
  3. ^ a b "Entrez Gene: SLC4A4 solute carrier family 4, sodium bicarbonate cotransporter, member 4". 
  4. ^ Suzuki M, Van Paesschen W, Stalmans I, Horita S, Yamada H, Bergmans BA, Legius E, Riant F, De Jonghe P, Li Y, Sekine T, Igarashi T, Fujimoto I, Mikoshiba K, Shimadzu M, Shiohara M, Braverman N, Al-Gazali L, Fujita T, Seki G (September 2010). "Defective membrane expression of the Na(+)-HCO(3)(-) cotransporter NBCe1 is associated with familial migraine". Proc. Natl. Acad. Sci. U.S.A. 107 (36): 15963–8. doi:10.1073/pnas.1008705107. PMC 2936614. PMID 20798035. 
  5. ^ Zhu Q, Kao L, Azimov R, Newman D, Liu W, Pushkin A, Abuladze N, Kurtz I (April 2010). "Topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis". J. Biol. Chem. 285 (18): 13416–26. doi:10.1074/jbc.M109.093286. PMC 2859501. PMID 20197274. 

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.