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Gene Review

ATP6V0A4  -  ATPase, H+ transporting, lysosomal V0...

Homo sapiens

Synonyms: A4, ATP6N1B, ATP6N2, RDRTA2, RTA1C, ...
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Disease relevance of ATP6V0A4


Psychiatry related information on ATP6V0A4


High impact information on ATP6V0A4

  • The importance in final urinary acidification along the collecting system is highlighted by monogenic defects in two subunits (ATP6V0A4, ATP6V1B1) of the vacuolar H(+)-ATPase in patients with distal renal tubular acidosis [8].
  • Mutations in ATP6N1B, encoding a new kidney vacuolar proton pump 116-kD subunit, cause recessive distal renal tubular acidosis with preserved hearing [9].
  • Immunofluorescence studies in human kidney cortex revealed that ATP6N1B localizes almost exclusively to the apical surface of -intercalated cells [9].
  • 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 [9].
  • One hundred fifty-four unrelated French Caucasian subjects were typed for 11 RFLPs at or near the APOA1-C3-A4 gene cluster on the long arm of chromosome 11 [10].

Chemical compound and disease context of ATP6V0A4

  • Human data raised the possibility that coronary heart disease is associated with mutations in the apolipoprotein gene cluster APOA1/C3/A4 that result in multideficiency of cluster-encoded apolipoproteins and hypoalphalipoproteinemia [11].

Biological context of ATP6V0A4

  • These findings provide further evidence for genetic heterogeneity in rdRTA, extend the spectrum of disease causing mutations in ATP6V1B1 and ATP6V0A4, and show ATP6V0A4 expression within the cochlea for the first time [3].
  • Linkage analysis of seven novel SNPs and five polymorphic markers in, and tightly linked to, ATP6V1B1 and ATP6V0A4 suggested that four families do not link to either locus, providing strong evidence for additional genetic heterogeneity [3].
  • That a4 W520L affects both Vo and V1 subunits is a unique phenotype for any V-ATPase subunit mutation and supports the concerted pathway for V-ATPase assembly in vivo [12].
  • We have isolated and sequenced genomic clones of the human Fc gamma RIII-A and Fc gamma RIII-B genes, located their transcription initiation sites, identified a different organization of their 5' regions, and demonstrated four distinct classes of Fc gamma RIII-A transcripts (a1-a4) compared with a single class of Fc gamma RIII-Bb1 transcripts [13].
  • These studies establish the importance of the VPH1 gene and vesicular acidification in the virulence of C. neoformans [14].

Anatomical context of ATP6V0A4

  • We show here that ATP6V0A4 is expressed within the human inner ear [3].
  • Immunoblots confirmed wild type levels for V-ATPase a, A, and B subunits on vacuolar membranes. a4 G812R resulted in defective growth on selective media with V-ATPase hydrolytic and pumping activity decreased by 83-85% yet with wild type levels of a, A, and B subunits on vacuolar membranes [12].
  • This protein shares high sequence homology to the yeast vacuolar H(+)-ATPase subunit, Vph1p, and the 116 kDa proton pump of the rat and bovine synaptic vesicle, Vpp1 [15].
  • The chondrocyte cell lines C28/I2, C20/A4, and T/C28a2/a4 expressed functionally active VEGFR-2 [16].
  • The same changes in the inward-rectifier K+ channel were also observed in a4 2 blastomeres which were induced by cell contact with an A4-1 blastomere [17].

Associations of ATP6V0A4 with chemical compounds

  • To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well-established roles in influencing plasma HDL-cholesterol and triglyceride concentrations [18].
  • Insertional mutagenesis and plasmid rescue were used to identify the VPH1 gene by screening for mutants defective in laccase activity [14].
  • A novel intragenetic PvuII marker in the human neuronal nicotinic acetylcholine receptor a4 subunit gene (CHRNA4). Mutation and polymorphism report no. 62. Online [19].
  • Moreover, expression of the paralogous group 4 genes (HOX A4, HOX B4, HOX C4, and HOX D4), together with that of isolated genes in the network, appears to discriminate between white and brown adipose tissue [20].
  • Inactivating mutations introduced at the A4/A3 elements, binding sites for the glucose-regulated homeodomain transcription factor PDX-1, did not diminish the response to Ex-4, although a marked reduction of basal promoter activity was observed [21].

Other interactions of ATP6V0A4


Analytical, diagnostic and therapeutic context of ATP6V0A4


  1. Molecular cloning and characterization of novel tissue-specific isoforms of the human vacuolar H(+)-ATPase C, G and d subunits, and their evaluation in autosomal recessive distal renal tubular acidosis. Smith, A.N., Borthwick, K.J., Karet, F.E. Gene (2002) [Pubmed]
  2. Genetic Investigation of Autosomal Recessive Distal Renal Tubular Acidosis: Evidence for Early Sensorineural Hearing Loss Associated with Mutations in the ATP6V0A4 Gene. Vargas-Poussou, R., Houillier, P., Le Pottier, N., Strompf, L., Loirat, C., Baudouin, V., Macher, M.A., Déchaux, M., Ulinski, T., Nobili, F., Eckart, P., Novo, R., Cailliez, M., Salomon, R., Nivet, H., Cochat, P., Tack, I., Fargeot, A., Bouissou, F., Kesler, G.R., Lorotte, S., Godefroid, N., Layet, V., Morin, G., Jeunemaître, X., Blanchard, A. J. Am. Soc. Nephrol. (2006) [Pubmed]
  3. Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss. Stover, E.H., Borthwick, K.J., Bavalia, C., Eady, N., Fritz, D.M., Rungroj, N., Giersch, A.B., Morton, C.C., Axon, P.R., Akil, I., Al-Sabban, E.A., Baguley, D.M., Bianca, S., Bakkaloglu, A., Bircan, Z., Chauveau, D., Clermont, M.J., Guala, A., Hulton, S.A., Kroes, H., Li Volti, G., Mir, S., Mocan, H., Nayir, A., Ozen, S., Rodriguez Soriano, J., Sanjad, S.A., Tasic, V., Taylor, C.M., Topaloglu, R., Smith, A.N., Karet, F.E. J. Med. Genet. (2002) [Pubmed]
  4. Expression of gene MAGE-A4 in Reed-Sternberg cells. Chambost, H., Van Baren, N., Brasseur, F., Godelaine, D., Xerri, L., Landi, S.J., Theate, I., Plumas, J., Spagnoli, G.C., Michel, G., Coulie, P.G., Olive, D. Blood (2000) [Pubmed]
  5. Alzheimer A4 peptide, gamma-trace, leukoencephalopathy, and hereditary cerebral hemorrhage with amyloidosis-Dutch type. Haan, J., Roos, R.A. Ann. Neurol. (1991) [Pubmed]
  6. A quantitative study of the coincidence of blood vessels and A4 protein deposits in Alzheimer's disease. Luthert, P.J., Williams, J.A. Neurosci. Lett. (1991) [Pubmed]
  7. Large amounts of neocortical beta A4 deposits without neuritic plaques nor tangles in a psychometrically assessed, non-demented person. Delaère, P., Duyckaerts, C., Masters, C., Beyreuther, K., Piette, F., Hauw, J.J. Neurosci. Lett. (1990) [Pubmed]
  8. Renal vacuolar H+-ATPase. Wagner, C.A., Finberg, K.E., Breton, S., Marshansky, V., Brown, D., Geibel, J.P. Physiol. Rev. (2004) [Pubmed]
  9. Mutations in ATP6N1B, encoding a new kidney vacuolar proton pump 116-kD subunit, cause recessive distal renal tubular acidosis with preserved hearing. Smith, A.N., Skaug, J., Choate, K.A., Nayir, A., Bakkaloglu, A., Ozen, S., Hulton, S.A., Sanjad, S.A., Al-Sabban, E.A., Lifton, R.P., Scherer, S.W., Karet, F.E. Nat. Genet. (2000) [Pubmed]
  10. Extended haplotypes and linkage disequilibrium between 11 markers at the APOA1-C3-A4 gene cluster on chromosome 11. Benlian, P., Boileau, C., Loux, N., Pastier, D., Masliah, J., Coulon, M., Nigou, M., Ragab, A., Guimard, J., Ruidavets, J.B. Am. J. Hum. Genet. (1991) [Pubmed]
  11. Characterization of a new mouse model for human apolipoprotein A-I/C-III/A-IV deficiency. Mezdour, H., Larigauderie, G., Castro, G., Torpier, G., Fruchart, J., Nowak, M., Fruchart, J.C., Rouis, M., Maeda, N. J. Lipid Res. (2006) [Pubmed]
  12. Effects of human a3 and a4 mutations that result in osteopetrosis and distal renal tubular acidosis on yeast V-ATPase expression and activity. Ochotny, N., Van Vliet, A., Chan, N., Yao, Y., Morel, M., Kartner, N., von Schroeder, H.P., Heersche, J.N., Manolson, M.F. J. Biol. Chem. (2006) [Pubmed]
  13. The human low affinity immunoglobulin G Fc receptor III-A and III-B genes. Molecular characterization of the promoter regions. Gessner, J.E., Grussenmeyer, T., Kolanus, W., Schmidt, R.E. J. Biol. Chem. (1995) [Pubmed]
  14. Multiple virulence factors of Cryptococcus neoformans are dependent on VPH1. Erickson, T., Liu, L., Gueyikian, A., Zhu, X., Gibbons, J., Williamson, P.R. Mol. Microbiol. (2001) [Pubmed]
  15. Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H(+)-ATPase-like protein. Tulin, E.E., Onoda, N., Hasegawa, M., Nomura, H., Kitamura, T. Oncogene (2002) [Pubmed]
  16. Vascular endothelial growth factor (VEGF) induces matrix metalloproteinase expression in immortalized chondrocytes. Pufe, T., Harde, V., Petersen, W., Goldring, M.B., Tillmann, B., Mentlein, R. J. Pathol. (2004) [Pubmed]
  17. Neural induction suppresses early expression of the inward-rectifier K+ channel in the ascidian blastomere. Okamura, Y., Takahashi, K. J. Physiol. (Lond.) (1993) [Pubmed]
  18. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons. Wang, Q.F., Liu, X., O'Connell, J., Peng, Z., Krauss, R.M., Rainwater, D.L., VandeBerg, J.L., Rubin, E.M., Cheng, J.F., Pennacchio, L.A. Hum. Mol. Genet. (2004) [Pubmed]
  19. A novel intragenetic PvuII marker in the human neuronal nicotinic acetylcholine receptor a4 subunit gene (CHRNA4). Mutation and polymorphism report no. 62. Online. Iwata, H., Hirose, S., Akiyoshi, H., Kaneko, S., Mitsudome, A. Hum. Mutat. (1999) [Pubmed]
  20. HOX gene network is involved in the transcriptional regulation of in vivo human adipogenesis. Cantile, M., Procino, A., D'Armiento, M., Cindolo, L., Cillo, C. J. Cell. Physiol. (2003) [Pubmed]
  21. Exendin-4 as a stimulator of rat insulin I gene promoter activity via bZIP/CRE interactions sensitive to serine/threonine protein kinase inhibitor Ro 31-8220. Chepurny, O.G., Hussain, M.A., Holz, G.G. Endocrinology (2002) [Pubmed]
  22. Degradation of the Gluconeogenic Enzyme Fructose-1, 6-Bisphosphatase is Dependent on the Vacuolar ATPase. Liu, J., Brown, C.R., Chiang, H.L. Autophagy. (2005) [Pubmed]
  23. The a-subunit of the V-type H+-ATPase interacts with phosphofructokinase-1 in humans. Su, Y., Zhou, A., Al-Lamki, R.S., Karet, F.E. J. Biol. Chem. (2003) [Pubmed]
  24. Structure of a legume lectin from the bark of Robinia pseudoacacia and its complex with N-acetylgalactosamine. Rabijns, A., Verboven, C., Rougé, P., Barre, A., Van Damme, E.J., Peumans, W.J., De Ranter, C.J. Proteins (2001) [Pubmed]
  25. Exercise-induced STV1 elevation: a sign of right ventricular dysfunction in recent inferior myocardial infarction. Kobayashi, H., Tsuchihashi, K., Hashimoto, A., Nagao, K., Tanaka, S., Shimamoto, K., Iimura, O. The Canadian journal of cardiology. (1994) [Pubmed]
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