ATP6B1 encodes one of the B-subunit isoforms of vacuolar ATPase (V-ATPase), which facilitates acidification of intracellular organelles. V-ATPase consists of a transmembrane and a cytosolic domain, both of which are composed of multiple subunits. The protein encoded by ATP6B1 is part of the V1 cytosolic domain that holds the catalytic site. V-ATPase is expressed throughout the body and is involved in various intracellular processes such as receptor-mediated endocytosis, synaptic vesicle proton gradient generation and protein sorting.
Mutations in the ATP6B1 gene is linked to nephrolithiasis and distal renal tubular acidosis associated with sensorineural deafness.
Stover et al. (2002) identified a mutation in the ATP6V1B1 that caused recessive distal renal tubular acidosis with progressive nerve deafness in a 41-year-old female patient from a consanguineous Moroccan family. The mutation involved the insertion of a C residue at the position 1155-1156 of the gene leading to the premature stop codon in the ATP6V1B1 protein (I386-frameshift-X441).
Stover et al. (2002) identified mutations in the B1 subunit gene ATP6V1B1 that caused recessive distal renal tubular acidosis with progressive nerve deafness in four patients from Saudi Arabia. All patients were from consanguineous families and their age ranged between 10-15 years. The first case is of a Saudi female patient who carries the insertion of a C residue at the position 1155-1156 of the gene leading to the modification of the ATP6V1B1 protein (I386-frame shift-X441). Stover et al. (2002) proposed that the presence of this mutation in patients from North Africa and Sicily could be because of a genetic drift as there was an Arab domination in those regions centuries ago. The second case involved a patient with a deletion of the C residue at position 497 of the ATP6V1B1 gene leading to a frame shift in the protein (T166-frame shift-X174). The third and fourth cases involved two Saudis (female and a male) with the mutation 1037 (C-G) leading to a modified ATP6V1B1 protein (P346R). The mutations in all four cases were homozygous. Stover et al. (2002) also studied 13 unrelated and unaffected subjects from Saudi Arabia. Four intragenic single nucleotide polymorphisms in ATP6V1B1 previously identified in Saudi Arabian patients during mutation screening, were characterized for use in genotyping. The SNPs analyzed included 138 (T-C), IVS-3- +117 (C-A), 481 (G-A), and 1002 (C-T). All these polymorphisms were common, were found to be in Hardy-Weinberg equilibrium in all control chromosomes, and were found to be neutral biallelic polymorphisms. In addition, three novel missense alterations in the ATP6V1B1 gene were also observed in control subjects. These included 90 (C-T), and 368 (G-T), and 469 (C-T).