Functional characterization of nonsynonymous single nucleotide polymorphisms in the electrogenic Na+-HCO 3 - Cotransporter NBCe1A

Osamu Yamazaki, Hideomi Yamada, Masashi Suzuki, Shoko Horita, Ayumi Shirai, Motonobu Nakamura, George Seki, Toshiro Fujita

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


The electrogenic Na+-HCO 3 - cotransporter NBCe1 encoded by SLC4A4 plays essential roles in the regulation of intracellular/extracellular pH. Homozygous mutations in NBCe1 cause proximal renal tubular acidosis associated with ocular abnormalities. In the present study, we tried to perform functional characterization of the four nonsynonymous single nucleotide polymorphisms (SNPs), E122G, S356Y, K558R, and N640I in NBCe1A. Functional analysis in Xenopus oocytes revealed that while the K558R variant had a significantly reduced transport activity corresponding to 47% of the wild-type activity, the remaining variants E122G, S356Y, and N640I did not change the NBCe1A activity. Apparent Na+ affinity of K558R was not different from that of wild-type NBCe1A. Immunohistological analyses in HEK293 cells and MDCK cells indicated that none of these SNPs changed the trafficking behaviors of NBCe1A. Functional analysis in HEK293 cells also revealed that only the K558R variant had a reduced transport activity, corresponding to 41-47% of the wild-type activity. From these results, we conclude that among four SNPs, only the K558R variant, which is predicted to lie in transmembrane segment 5, significantly reduces the NBCe1A activity without changing the trafficking behavior or the apparent extracellular Na+ affinity.

Original languageEnglish
Pages (from-to)249-259
Number of pages11
JournalPflugers Archiv European Journal of Physiology
Issue number2
Publication statusPublished - 2011 Feb
Externally publishedYes


  • Renal proximal tubules
  • SLC4A4
  • SNP
  • pRTA

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)


Dive into the research topics of 'Functional characterization of nonsynonymous single nucleotide polymorphisms in the electrogenic Na<sup>+</sup>-HCO <sub>3</sub> <sup>-</sup> Cotransporter NBCe1A'. Together they form a unique fingerprint.

Cite this