ATP6V1B1

ATP6V1B1 is a gene that encodes a subunit of the vacuolar H+-ATPase (V-ATPase) proton pump, which is essential for regulating acidity in cells. This protein helps manage the body's acid-base balance in the kidneys and maintains the pH of the fluid in the inner ear.

Mutations in the ATP6V1B1 gene cause distal renal tubular acidosis (dRTA), which can lead to metabolic acidosis, kidney damage, and sensorineural hearing loss (SNHL). 

What is ATP6V1B1?

ATP6V1B1 is a gene that provides instructions for making a subunit of the vacuolar H+-ATPase (V-ATPase), a protein complex that pumps hydrogen ions (protons) across membranes to regulate cell acidity (pH). This is foundational to normal biological functions. V-ATPase is found in the kidneys and inner ear.

In the kidneys, it helps regulate acid-base balance by controlling proton excretion in urine. In the inner ear, it maintains the proper pH of the fluid needed for hearing. 

Mutations in ATP6V1B1 can lead to distal renal tubular acidosis (dRTA), which causes metabolic acidosis and kidney damage. It also causes sensorineural hearing loss (SNHL), which usually develops early in life. 

Mutations in the ATP6V1B1 gene can result in earlier hearing loss than mutations in similar genes, such as ATP6V0A4. Early genetic screening can help with timely diagnosis and treatment, improving outcomes.

Clinical Implications of ATP6V1B1 Mutations

Mutations in the ATP6V1B1 gene, which encodes the B1 subunit of the V-ATPase proton pump, are a primary cause of autosomal recessive distal renal tubular acidosis (dRTA). 

This condition is characterized by hyperchloremic metabolic acidosis, hypokalemia, nephrocalcinosis, polydipsia and polyuria, bone weakness, vomiting and dehydration, and failure to thrive, often presenting in infancy. Sensorineural hearing loss (SNHL) is commonly associated with ATP6V1B1 mutations, typically with early onset, though the severity of hearing loss can vary.

ATP6V1B1 mutations impair the V-ATPase function, disrupting proton secretion in both renal and cochlear cells, leading to characteristic renal and auditory symptoms. Additionally, mutations can result in enlarged vestibular aqueduct (EVA), a condition associated with hearing loss.

Genetic testing for ATP6V1B1 mutations is essential for diagnosing dRTA, particularly in high-risk populations. Identifying mutations early allows for timely intervention, including treatments for metabolic acidosis and hypokalemia, and potentially hearing aids or cochlear implants for SNHL. 

Regular monitoring of kidney function is also important, as chronic kidney disease (CKD) may develop over time, particularly in patients with long-standing disease.

Who Should Get ATP6V1B1 Tested?

ATP6V1B1 testing is typically indicated for patients with a family history of genetic disorders involving ATP6V1B1 mutations or for those who present with symptoms of metabolic acidosis or unexplained hearing loss. 

Testing especially benefits infants and children, particularly for early screening of genetic conditions such as dRTA.

For adults presenting with symptoms like chronic fatigue, muscle weakness, and metabolic acidosis, especially if hearing loss is present, ATP6V1B1 testing may help clarify the underlying cause and inform appropriate treatment strategies.

Test Procedure and Interpretation

The following section outlines the testing procedure and results interpretation: 

Testing Procedure and Preparation Requirements

ATP6V1B1 testing typically involves blood or urine samples. Genetic testing may also be performed to identify mutations in the ATP6V1B1 gene. No special preparation is usually required, though additional tests to evaluate kidney function or electrolytes may be helpful.

Normal Reference Ranges

Normal reference ranges for ATP6V1B1 genetic testing are considered to be without mutations that can alter the activity of the V-ATPase proton pump.

Clinical Implications of Positive ATP6V1B1 Mutations

The clinical implications of a positive ATP6V1B1 mutation test result may indicate underlying issues that warrant further investigation. 

Individuals inheriting two copies (autosomal recessive) of the mutated ATP6V1B1 gene are more likely to develop autosomal recessive distal renal tubular acidosis, and may present with associated symptoms such as hyperchloremic metabolic acidosis, hypokalemia, nephrocalcinosis, polydipsia and polyuria, bone weakness, vomiting and dehydration.

Diagnosis and Treatment of dRTA

Genetic testing for ATP6V1B1 is only part of the diagnostic process for dRTA.

Doctors rely on a combination of symptoms, lab tests, and genetic testing to diagnose dRTA. Mutations in genes such as ATP6V1B1, ATP6V0A4, and SLC4A1 are often involved. 

The main treatment for dRTA is alkali therapy, which helps correct the body's acid imbalance. This treatment can prevent complications like bone weakness and kidney damage and help children grow normally. 

Different types of alkali medications, like potassium citrate and sodium bicarbonate, are used depending on the patient's needs. Newer medications, like ADV7103, offer the advantage of needing fewer doses and can help improve metabolic control.

However, hearing loss caused by dRTA requires separate treatment, often including hearing aids or cochlear implants. Ongoing care focuses on making sure the patient sticks to their treatment plan to prevent further kidney damage, maintain normal growth, and manage hearing loss.

Order Genetic Testing

Click here to compare genetic test panels and order genetic testing for health-related SNPs.