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These include the AE1 Cl<jats:sup>\u2212<\/jats:sup>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> exchanger of the basolateral membrane and at least two subunits of the apical membrane vacuolar (v)H<jats:sup>+<\/jats:sup>-ATPase, the V<jats:sub>1<\/jats:sub> subunit B1 (associated with deafness) and the V<jats:sub>0<\/jats:sub> subunit a4. Recessive proximal RTA with ocular disease arises from mutations in the electrogenic Na<jats:sup>+<\/jats:sup>-bicarbonate cotransporter NBC1 of the proximal tubular cell basolateral membrane. Recessive mixed proximal-distal RTA accompanied by osteopetrosis and mental retardation is associated with mutations in cytoplasmic carbonic anhydrase II. The metabolic alkalosis of congenital chloride-losing diarrhea is caused by mutations in the DRA Cl<jats:sup>\u2212<\/jats:sup>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> exchanger of the ileocolonic apical membrane. Recessive osteopetrosis is caused by deficient osteoclast acid secretion across the ruffled border lacunar membrane, the result of mutations in the vH<jats:sup>+<\/jats:sup>-ATPase V<jats:sub>0<\/jats:sub> subunit or in the CLC-7 Cl<jats:sup>\u2212<\/jats:sup> channel. X-linked nephrolithiasis and engineered deficiencies in some other CLC Cl<jats:sup>\u2212<\/jats:sup> channels are thought to represent defects of organellar acidification. Study of acid-base transport disease-associated mutations should enhance our understanding of protein structure-function relationships and their impact on the physiology of cell, tissue, and organism. <\/jats:p>","DOI":"10.1146\/annurev.physiol.64.092801.141759","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T11:41:01Z","timestamp":1027770061000},"page":"899-923","source":"Crossref","is-referenced-by-count":147,"title":["Genetic Diseases of Acid-Base Transporters"],"prefix":"10.1146","volume":"64","author":[{"given":"Seth L.","family":"Alper","sequence":"first","affiliation":[{"name":"Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Department of Medicine and Cell Biology, Harvard Medical School Boston, Massachusetts 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"22","reference":[{"key":"b1","volume-title":"The Kidney.","author":"Seldin D","year":"2001"},{"key":"b2","unstructured":"Bevensee M, Aronson PS, Alper SL, Boron WF. 2001. 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