Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The multi-subunit H+-ATPase pump is present at particularly high density on the apical (luminal) surface of -intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification. The complete subunit composition of the apical ATPase, however, has not been fully agreed upon. Functional failure of -intercalated cells results in a group of disorders, the distal renal tubular acidoses (dRTA), whose features include metabolic acidosis accompanied by disturbances of potassium balance, urinary calcium solubility, bone physiology and growth. Mutations in the gene encoding the B-subunit of the apical pump (ATP6B1) cause dRTA accompanied by deafness. We previously localized a gene for dRTA with preserved hearing to 7q33-34 (ref. 4). We report here the identification of this gene, ATP6N1B, which encodes an 840 amino acid novel kidney-specific isoform of ATP6N1A, the 116-kD non-catalytic accessory subunit of the proton pump. Northern-blot analysis demonstrated ATP6N1B expression in kidney but not other main organs. Immunofluorescence studies in human kidney cortex revealed that ATP6N1B localizes almost exclusively to the apical surface of -intercalated cells. We screened nine dRTA kindreds with normal audiometry that linked to the ATP6N1B locus, and identified different homozygous mutations in ATP6N1B in eight. These include nonsense, deletion and splice-site changes, all of which will truncate the protein. Our findings identify a new kidney-specific proton pump 116-kD accessory subunit that is highly expressed in proton-secreting cells in the distal nephron, and illustrate its essential role in normal vectorial acid transport into the urine by the kidney.
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PMID:Mutations in ATP6N1B, encoding a new kidney vacuolar proton pump 116-kD subunit, cause recessive distal renal tubular acidosis with preserved hearing. 1097 52

A large proportion of autosomal recessive distal renal tubular acidosis (RTA) is associated with mutations in the ATP6B1 gene encoding the B1 subunit of H+-ATPase. H+-ATPase is one of the key membrane transporters for net acid excretion in the alpha-intercalated cells of the medullary collecting duct. Sensorineural hearing loss frequently accompanies this type of distal RTA. Mutational analysis of the ATP6B1 gene in a 9-year-old Korean boy with distal RTA and sensorineural hearing loss found 2 heterozygous missense point mutations. Although a single case report, this is the second report documenting ATP6B1 mutations in recessive distal RTA with sensorineural hearing loss after the original report by Karet et al and confirms the novelty of these mutations.
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PMID:ATP6B1 gene mutations associated with distal renal tubular acidosis and deafness in a child. 1250 Feb 43