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ATP6V0A4 gene

ATPase H+ transporting V0 subunit a4

Normal Function

The ATP6V0A4 gene provides instructions for making a part (subunit) of a large protein complex known as vacuolar H+-ATPase (V-ATPase). V-ATPases are a group of similar complexes that act as pumps to move positively charged hydrogen atoms (protons) across membranes. Because acids are substances that can "donate" protons to other molecules, this movement of protons helps regulate the relative acidity (pH) of cells and their surrounding environment. Tight control of pH is necessary for most biological reactions to proceed properly.

The V-ATPase that includes the subunit produced from the ATP6V0A4 gene is found in the inner ear and in nephrons, which are the functional structures within the kidneys. The kidneys filter waste products from the blood and remove them in urine. They also reabsorb needed nutrients and release them back into the blood. Each nephron consists of two parts: a renal corpuscle (also known as a glomerulus) that filters the blood, and a renal tubule that reabsorbs substances that are needed and eliminates unneeded substances in urine. The V-ATPase is involved in regulating the amount of acid that is removed from the blood into the urine, and also in maintaining the proper pH of the fluid in the inner ear (endolymph).

Health Conditions Related to Genetic Changes

Renal tubular acidosis with deafness

Several ATP6V0A4 gene mutations have been identified in people with renal tubular acidosis with deafness, a disorder involving excess acid in the blood (metabolic acidosis), bone weakness, and hearing loss caused by changes in the inner ear (sensorineural hearing loss).

Mutations in the ATP6V0A4 gene impair the function of the V-ATPase proton pump. As a result, the kidneys are less able to control the acidity of the blood, which leads to bone weakness caused by loss of bone minerals (demineralization) and other consequences of metabolic acidosis. The body's capability to control the pH of the fluid in the inner ear is also impaired, resulting in sensorineural hearing loss.

More About This Health Condition

Other disorders

ATP6V0A4 gene mutations have also been identified in people with renal tubular acidosis who have normal hearing when diagnosed, usually in infancy or early childhood. However, hearing loss sometimes does not develop until adulthood in renal tubular acidosis with deafness (described above), so some of these individuals are later found to have that disorder.

Other Names for This Gene

  • A4
  • ATP6N1B
  • ATP6N2
  • ATPase, H+ transporting, lysosomal (vacuolar proton pump) non-catalytic accessory protein 1B
  • ATPase, H+ transporting, lysosomal V0 subunit a4
  • H(+)-transporting two-sector ATPase, noncatalytic accessory protein 1B
  • RdRTA2
  • RTA1C
  • STV1
  • V-ATPase 116 kDa
  • V-type proton ATPase 116 kDa subunit a
  • V-type proton ATPase 116 kDa subunit a isoform 4
  • vacuolar proton pump 116 kDa accessory subunit
  • vacuolar proton pump, subunit 2
  • vacuolar proton translocating ATPase 116 kDa subunit a kidney isoform
  • VPH1
  • VPP2

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Gene and Variant Databases


  • Alper SL. Familial renal tubular acidosis. J Nephrol. 2010 Nov-Dec;23 Suppl 16:S57-76. Citation on PubMed
  • Andreucci E, Bianchi B, Carboni I, Lavoratti G, Mortilla M, Fonda C, Bigozzi M, Genuardi M, Giglio S, Pela I. Inner ear abnormalities in four patients with dRTA and SNHL: clinical and genetic heterogeneity. Pediatr Nephrol. 2009 Nov;24(11):2147-53. doi: 10.1007/s00467-009-1261-3. Epub 2009 Jul 29. Citation on PubMed
  • Batlle D, Haque SK. Genetic causes and mechanisms of distal renal tubular acidosis. Nephrol Dial Transplant. 2012 Oct;27(10):3691-704. doi: 10.1093/ndt/gfs442. Citation on PubMed
  • Li X, Chai Y, Tao Z, Li L, Huang Z, Li Y, Wu H, Yang T. Novel mutations in ATP6V0A4 are associated with atypical progressive sensorineural hearing loss in a Chinese patient with distal renal tubular acidosis. Int J Pediatr Otorhinolaryngol. 2012 Jan;76(1):152-4. doi: 10.1016/j.ijporl.2011.10.017. Epub 2011 Nov 16. Citation on PubMed
  • Stover EH, Borthwick KJ, Bavalia C, Eady N, Fritz DM, Rungroj N, Giersch AB, Morton CC, Axon PR, Akil I, Al-Sabban EA, Baguley DM, Bianca S, Bakkaloglu A, Bircan Z, Chauveau D, Clermont MJ, Guala A, Hulton SA, Kroes H, Li Volti G, Mir S, Mocan H, Nayir A, Ozen S, Rodriguez Soriano J, Sanjad SA, Tasic V, Taylor CM, Topaloglu R, Smith AN, Karet FE. Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss. J Med Genet. 2002 Nov;39(11):796-803. doi: 10.1136/jmg.39.11.796. Citation on PubMed or Free article on PubMed Central
  • Vargas-Poussou R, Houillier P, Le Pottier N, Strompf L, Loirat C, Baudouin V, Macher MA, Dechaux M, Ulinski T, Nobili F, Eckart P, Novo R, Cailliez M, Salomon R, Nivet H, Cochat P, Tack I, Fargeot A, Bouissou F, Kesler GR, Lorotte S, Godefroid N, Layet V, Morin G, Jeunemaitre X, Blanchard A. Genetic investigation of autosomal recessive distal renal tubular acidosis: evidence for early sensorineural hearing loss associated with mutations in the ATP6V0A4 gene. J Am Soc Nephrol. 2006 May;17(5):1437-43. doi: 10.1681/ASN.2005121305. Epub 2006 Apr 12. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.