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ATP6V1B1

ATPase H+ transporting V1 subunit B1

The ATP6V1B1 gene provides instructions for a vital subunit of the vacuolar H+-ATPase (V-ATPase) protein complex, essential for maintaining proper pH balance within the body, particularly in the kidneys and inner ear. The ATP6V1B1 gene is critical for encoding a component of the V-ATPase, a proton pump responsible for moving hydrogen ions across cellular membranes.

Chromosome 2p13.3 Autosomal recessive HGNC:853 Tier C
ATP6V1B1 2p13.3 p arm q arm 2

ATP6V1B1 is located on the short (p) arm of chromosome 2, at band 2p13.3. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 2 in the library →

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Clinical tests that include this

Carrier Screening panel
ATP6V1B1 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The ATP6V1B1 gene codes for a specific subunit of the vacuolar H+-ATPase (V-ATPase) protein complex. V-ATPases are crucial cellular machines that transport positively charged hydrogen ions, known as protons, across biological membranes. This proton movement is fundamental for controlling the acidity (pH) within cells and their surrounding environments, a process vital for numerous biological reactions.

What the gene does

The V-ATPase protein complex, which includes the subunit produced from the ATP6V1B1 gene, acts as a proton pump. Its primary role involves moving protons, thereby regulating pH in specific organs such as the kidneys and the inner ear. In the kidneys, V-ATPases contribute to removing excess acid from the blood and excreting it into the urine. They also play a role in reabsorbing necessary substances back into the bloodstream. Within the inner ear, this protein helps maintain the correct pH of the endolymph fluid, which is essential for proper hearing. Impaired function of this V-ATPase can lead to an accumulation of acid in the blood and issues with inner ear function.

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Chromosome location

The ATP6V1B1 gene is located on chromosome 2, specifically at position 2p13.3. This genomic address specifies its precise position within the human genome.

Protein structure

The ATP6V1B1 protein is composed of 513 amino acids. It features a PDZ-binding motif located at amino acids 510-513. This motif typically mediates interactions with PDZ domain-containing proteins, often involved in protein scaffolding and signal transduction.

Domain map · 513 amino acids
PDZ-binding (510–513)PDZ-binding510–5131~257513
Motif - short conserved sequence
🧬 Explore 3D structure on AlphaFold
UniProt:P15313Length:513 aaStructure:AlphaFold

Key variants

Variants within the ATP6V1B1 gene can alter the structure or function of the encoded V-ATPase subunit. These genetic changes can impair the protein's ability to properly regulate pH, leading to various health implications. The type and location of a variant can influence the severity and specific manifestations of associated conditions.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for ATP6V1B1.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1143+2T>C
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Renal tubular acidosis with progressive nerve deafness
c.1386C>A
single nucleotide variant
 p.Tyr462Ter Pathogenic/Likely pathogenic ★★☆☆ Renal tubular acidosis with progressive nerve deafness
c.343_349del
Deletion
 p.Thr115fs Pathogenic/Likely pathogenic ★★☆☆ Renal tubular acidosis with progressive nerve deafness
c.408del
Deletion
 p.Pro137fs Pathogenic ★★☆☆ Renal tubular acidosis with progressive nerve deafness
c.448C>T
single nucleotide variant
 p.Gln150Ter Pathogenic/Likely pathogenic ★★☆☆ Renal tubular acidosis with progressive nerve deafness
c.481del
Deletion
 p.Glu161fs Pathogenic/Likely pathogenic ★★☆☆ Renal tubular acidosis with progressive nerve deafness
c.541C>T
single nucleotide variant
 p.Gln181Ter Pathogenic/Likely pathogenic ★★☆☆ Renal tubular acidosis with progressive nerve deafness
c.687+1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Renal tubular acidosis with progressive nerve deafness
c.687+1G>T
single nucleotide variant
 - Pathogenic ★★☆☆ Renal tubular acidosis with progressive nerve deafness
c.823A>C
single nucleotide variant
 p.Thr275Pro Pathogenic/Likely pathogenic ★★☆☆ Renal tubular acidosis with progressive nerve deafness

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the ATP6V1B1 gene are associated with various health conditions, most notably Renal tubular acidosis type I (ATP6V1B1). This disorder is characterised by the body's inability to effectively remove acid, leading to an excess of acid in the blood (metabolic acidosis), alongside potential issues such as bone weakness and sensorineural hearing loss.

  • Renal tubular acidosis type I (ATP6V1B1)
    Renal
    AR
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Inheritance pattern

Conditions caused by pathogenic ATP6V1B1 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous ATP6V1B1 carrier status across ancestry groups?

UK clinical status

The ATP6V1B1 gene is recognised within the NHS Genomic Medicine Service due to its clinical significance. It is included in several Green RAG status panels in PanelApp, indicating strong evidence for its association with disease. These panels include DDG2P, Monogenic hearing loss (R67), Nephrocalcinosis or nephrolithiasis (R256), and Renal tubulopathies (R198).

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Monogenic hearing loss · R67 NHS GMS → Nephrocalcinosis or nephrolithiasis · R256 NHS GMS → Renal tubulopathies · R198 NHS GMS → DDG2P NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main function of the ATP6V1B1 gene?

The ATP6V1B1 gene provides instructions for making a subunit of the vacuolar H+-ATPase (V-ATPase) protein complex. This complex acts as a proton pump, moving hydrogen ions across cell membranes to regulate the body's pH balance, particularly in the kidneys and inner ear.

Which condition is primarily associated with ATP6V1B1 gene variants?

Variants in the ATP6V1B1 gene are primarily associated with Renal tubular acidosis type I (ATP6V1B1). This condition can lead to excess acid in the blood, bone weakness, and sensorineural hearing loss.

How does the ATP6V1B1 gene affect the kidneys?

In the kidneys, the protein produced by the ATP6V1B1 gene helps the V-ATPase remove excess acid from the blood and excrete it into the urine. It also assists in reabsorbing important nutrients, playing a key role in maintaining normal kidney function.

References

  1. Mohebbi N, Vargas-Poussou R, Hegemann SC. Homozygous and compound heterozygous mutations in the ATP6V1B1 gene in patients with renal tubular acidosis and sensorineural hearing loss. Clinical genetics. 2013. PMID: 22509993
  2. Batlle D, Haque SK. Genetic causes and mechanisms of distal renal tubular acidosis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2012. PMID: 23114896
  3. Alper SL. Familial renal tubular acidosis. Journal of nephrology. 2010. PMID: 21170890
  4. Sethi SK, Singh N, Gil H. Genetic studies in a family with distal renal tubular acidosis and sensorineural deafness. Indian pediatrics. 2009. PMID: 19478356
  5. Andreucci E, Bianchi B, Carboni I. Inner ear abnormalities in four patients with dRTA and SNHL: clinical and genetic heterogeneity. Pediatric nephrology (Berlin, Germany). 2009. PMID: 19639346
  6. Nikali K, Vanegas JJ, Burley MW. Extensive founder effect for distal renal tubular acidosis (dRTA) with sensorineural deafness in an isolated South American population. American journal of medical genetics. Part A. 2008. PMID: 18798332
  7. Gil H, Santos F, García E. Distal RTA with nerve deafness: clinical spectrum and mutational analysis in five children. Pediatric nephrology (Berlin, Germany). 2007. PMID: 17216496
  8. Stover EH, Borthwick KJ, Bavalia C. Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss. Journal of medical genetics. 2002. PMID: 12414817
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 13 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .