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Gene Review

SLC4A5  -  solute carrier family 4 (sodium...

Homo sapiens

Synonyms: Electrogenic sodium bicarbonate cotransporter 4, NBC4, NBCe2, Solute carrier family 4 member 5
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Disease relevance of SLC4A5

  • After resampling-based false discovery adjustment, SLC4A5, a sodium bicarbonate transporter, was identified as a primary candidate gene for hypertension [1].
  • NBC activity in oocytes, assayed as the Na(+)-dependent, HCO(3)(-)-mediated intracellular pH recovery from acidosis, indicated that NBC4 is a DIDS-inhibitable NBC [2].

High impact information on SLC4A5

  • Although exposure of NBC1-expressing oocytes to CO(2)/HCO(3)(-) resulted in immediate hyperpolarization, the NBC4-expressing oocytes did not show any alteration in membrane potential [2].
  • We propose that NBC4 is expressed in the thick ascending limb of the loop of Henle and mediates cellular HCO(3)(-) uptake in this segment [2].
  • Functional characterization of NBC4: a new electrogenic sodium-bicarbonate cotransporter [3].
  • One NBC protein (approximately 150 kDa) seems to be related to the kidney/pancreas/heart isoform NBC1, whereas the other protein (approximately 200 kDa) is related to the NBC4 isoform [4].
  • This information should allow the study of potential genomic alterations of DCTN1-SLC4A5 in patients with diseases mapping to this genomic region [5].

Biological context of SLC4A5

  • We have characterized the genomic organization of the human DCTN1-SLC4A5 locus which spans approximately 230 kilobases on chromosome 2p13 and contains 66 exons [5].
  • These results additionally confirm the involvement of SLC4A5 with blood pressure control, although the mechanism is still unclear [6].
  • To extend these findings, SLC4A5 SNPs were genotyped in an independent set of 96 Utah pedigrees of 1040 adult subjects at baseline, 760 of whom were followed longitudinally for 10 years [6].

Anatomical context of SLC4A5

  • The NaHCO3 cotransporter gene (SLC4A5) on chromosome 2 encodes a protein that transports sodium and bicarbonate across the cell membrane and regulates cellular pH [6].
  • The approximately 6 kb NBC4 transcript is moderately expressed in heart, with the highest expression in liver, testes and spleen [7].

Associations of SLC4A5 with chemical compounds

  • There was no evidence for compensation of abnormal SLC4A5 sodium transport by genotype-specific differences in sodium-lithium countertransport, lithium-potassium cotransport, altered plasma sodium, chloride, or CO2 levels [6].
  • Nephron segment distribution studies indicated that NBC4 is predominantly expressed in the medullary and cortical thick ascending limb of the loop of Henle [2].
  • The first of two putative stilbene binding motifs (K(M/L)(X)K) is lacking in NBC4 (amino acids 655-658) [7].
  • In addition, NBC4 lacks the lysine-rich C-terminus of NBC1 with which it is most homologous [7].
  • Unlike other members of the NBC family, NBC4 has a unique glycine-rich region (amino acids 438-485) [7].

Other interactions of SLC4A5


Analytical, diagnostic and therapeutic context of SLC4A5


  1. Positional identification of hypertension susceptibility genes on chromosome 2. Barkley, R.A., Chakravarti, A., Cooper, R.S., Ellison, R.C., Hunt, S.C., Province, M.A., Turner, S.T., Weder, A.B., Boerwinkle, E. Hypertension (2004) [Pubmed]
  2. Expression of the Na+-HCO-3 cotransporter NBC4 in rat kidney and characterization of a novel NBC4 variant. Xu, J., Wang, Z., Barone, S., Petrovic, M., Amlal, H., Conforti, L., Petrovic, S., Soleimani, M. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  3. Functional characterization of NBC4: a new electrogenic sodium-bicarbonate cotransporter. Sassani, P., Pushkin, A., Gross, E., Gomer, A., Abuladze, N., Dukkipati, R., Carpenito, G., Kurtz, I. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  4. Expression of Na+/HCO3- co-transporter proteins (NBCs) in rat and human skeletal muscle. Kristensen, J.M., Kristensen, M., Juel, C. Acta Physiol. Scand. (2004) [Pubmed]
  5. Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and p150(Glued). Pushkin, A., Abuladze, N., Newman, D., Tatishchev, S., Kurtz, I. Cytogenet. Cell Genet. (2001) [Pubmed]
  6. Sodium bicarbonate cotransporter polymorphisms are associated with baseline and 10-year follow-up blood pressures. Hunt, S.C., Xin, Y., Wu, L.L., Cawthon, R.M., Coon, H., Hasstedt, S.J., Hopkins, P.N. Hypertension (2006) [Pubmed]
  7. Cloning, characterization and chromosomal assignment of NBC4, a new member of the sodium bicarbonate cotransporter family. Pushkin, A., Abuladze, N., Newman, D., Lee, I., Xu, G., Kurtz, I. Biochim. Biophys. Acta (2000) [Pubmed]
  8. Two C-terminal variants of NBC4, a new member of the sodium bicarbonate cotransporter family: cloning, characterization, and localization. Pushkin, A., Abuladze, N., Newman, D., Lee, I., Xu, G., Kurtz, I. IUBMB Life (2000) [Pubmed]
  9. Expression and localization of rat NBC4c in liver and renal uroepithelium. Abuladze, N., Pushkin, A., Tatishchev, S., Newman, D., Sassani, P., Kurtz, I. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  10. Functional characterization of human NBC4 as an electrogenic Na+-HCO cotransporter (NBCe2). Virkki, L.V., Wilson, D.A., Vaughan-Jones, R.D., Boron, W.F. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
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