Missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis
نویسندگان
چکیده
Quansheng Zhu, Xuesi M. Shao, Liyo Kao, Rustam Azimov, Alan M. Weinstein, Debra Newman, Weixin Liu, and Ira Kurtz Division of Nephrology, Department of Medicine, University of California, Los Angeles, California; Department of Neurobiology, University of California, Los Angeles, California; Department of Physiology and Biophysics, Weill Medical College of Cornell University, Ithaca, New York; and Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, California
منابع مشابه
Missense mutations and proximal RTA. Have we reached a new threshold? Focus on "missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis".
Mutations in SLC4A4, the gene encoding the electrogenic Na(+)-HCO3(-) cotransporter NBCe1, cause severe proximal renal tubular acidosis (pRTA), growth retardation, decreased IQ, and eye and teeth abnormalities. Among the known NBCe1 mutations, the disease-causing mechanism of the T485S (NBCe1-A numbering) mutation is intriguing because the substituted amino acid, serine, is structurally and che...
متن کاملProximal renal tubular acidosis mediated by mutations in NBCe1-A: unraveling the transporter's structure-functional properties
NBCe1 belongs to the SLC4 family of base transporting membrane proteins that plays a significant role in renal, extrarenal, and systemic acid-base homeostasis. Recent progress has been made in characterizing the structure-function properties of NBCe1 (encoded by the SLC4A4 gene), and those factors that regulate its function. In the kidney, the NBCe1-A variant that is expressed on the basolatera...
متن کاملA novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects.
In humans and terrestrial vertebrates, the kidney controls systemic pH in part by absorbing filtered bicarbonate in the proximal tubule via an electrogenic Na+/HCO3- cotransporter (NBCe1/SLC4A4). Recently, human genetics revealed that NBCe1 is the major renal contributor to this process. Homozygous point mutations in NBCe1 cause proximal renal tubular acidosis (pRTA), glaucoma, and cataracts (I...
متن کاملG418-mediated ribosomal read-through of a nonsense mutation causing autosomal recessive proximal renal tubular acidosis.
Autosomal recessive proximal renal tubular acidosis is caused by mutations in the SLC4A4 gene encoding the electrogenic sodium bicarbonate cotransporter NBCe1-A. The mutations that have been characterized thus far result in premature truncation, mistargeting, or decreased function of the cotransporter. Despite bicarbonate treatment to correct the metabolic acidosis, extrarenal manifestations pe...
متن کاملProximal renal tubular acidosis and ocular pathology: a novel missense mutation in the gene (SLC4A4) for sodium bicarbonate cotransporter protein (NBCe1).
PURPOSE The electrogenic Na+/HCO3- cotransporter (NBCe1) plays a major role in renal bicarbonate absorption via proximal tubules and therefore is crucial for maintaining normal blood pH. The human gene for NBCe1 (SLC4A4) produces two major transcripts by alternative promoter usage (kNBCe1, originally cloned from kidney and pNBCe1, pancreatic/general form). Though rare, recessive SLC4A4 mutation...
متن کامل