Donate HERE and directly support v-ATPase medical research Click here!

Hi 👋⁠
  • Home
  • About Us
  • Get Involved
  • Research
    • OUR BOARD
    • DCP RESULTS
    • MD TALKS
    • LITERATURE
  • Family Resources
    • PATIENT REGISTRY
    • STUDIES
    • WHAT IS V-ATPASE
    • HUMAN DISEASES
    • GENETIC TESTING
    • OUR WARRIORS
    • TELL YOUR STORY
    • NEWSLETTER
    • FACEBOOK GROUP
  • Contact
  • More
    • Home
    • About Us
    • Get Involved
    • Research
      • OUR BOARD
      • DCP RESULTS
      • MD TALKS
      • LITERATURE
    • Family Resources
      • PATIENT REGISTRY
      • STUDIES
      • WHAT IS V-ATPASE
      • HUMAN DISEASES
      • GENETIC TESTING
      • OUR WARRIORS
      • TELL YOUR STORY
      • NEWSLETTER
      • FACEBOOK GROUP
    • Contact
Hi 👋⁠
  • Home
  • About Us
  • Get Involved
  • Research
    • OUR BOARD
    • DCP RESULTS
    • MD TALKS
    • LITERATURE
  • Family Resources
    • PATIENT REGISTRY
    • STUDIES
    • WHAT IS V-ATPASE
    • HUMAN DISEASES
    • GENETIC TESTING
    • OUR WARRIORS
    • TELL YOUR STORY
    • NEWSLETTER
    • FACEBOOK GROUP
  • Contact

v-ATPase and Human Diseases

The v-ATPase has been implicated in several human diseases, primarily due to its crucial role in maintaining cellular pH homeostasis and its involvement in various cellular processes. 


The list of human diseases due to failure of v-ATPase is extensive due to its critical function in cells, and it depends on what subunits are affected and the tissues and cell types where their expression and function are more relevant. Some are Autosomal Dominant (AD), meaning variants in a single gene copy are sufficient to cause disease, while others are Autosomal Recessive (AR), meaning disease is only caused if the two gene copies are altered. 

ATP6V1C1

 The number of v-ATPase genes associated with human diseases has increased from 12 to 13.

As we prepare more information to share, please refer to this paper, which shows that ATP6V1C1 mutations cause a DOORS-like syndrome by increasing V-ATPase activity, disrupting lysosomes and autophagy, and affecting cilia: 

https://pubmed.ncbi.nlm.nih.gov/39210597/

    Examples of the relation between v-ATPase and human diseases

    Subunit - V0a

    Subunit - V0a

    Subunit - V0a

    Illustration of  v-ATPase complex highlighting the subunit ATP6V0A1

    ATP6V0A1 - AD/AR Developmental and epileptic encephalopathy

    Neurological disorder characterized by developmental delays and recurrent seizures. It typically manifests early in infancy and is often accompanied by cognitive and motor impairments. The condition involves a complex interplay of genetic and environmental factors, leading to a range of neurological symptoms and significant disability.

    Subunit - V0a

    Subunit - V0a

    Illustration of  v-ATPase complex highlighting the subunit ATP6V0A2

    ATP6V0A2 - AR Cutis Laxa (Type IIA)

    Rare genetic disorder characterized by loose, sagging skin with reduced elasticity. It affects the structure and function of elastic fibers in the skin and other connective tissues. Individuals with Cutis laxa (Type IIA) may experience respiratory, cardiovascular, and skeletal abnormalities, along with variable degrees of intellectual disability.

    Subunit - V0a

    Illustration of  v-ATPase complex highlighting the subunit ATP6V0A3

    TCIRG1/ATP6V0A3 - AR Osteopetrosis

    Rare genetic disorder that affects bone development and leads to increased bone density. It is characterized by defective osteoclast function, the cells responsible for breaking down and remodeling bone tissue. This results in brittle and abnormally dense bones, which can cause skeletal deformities, bone pain, and an increased risk of fractures.

    Subunit - V0c

    Illustration of  v-ATPase complex highlighting the subunit ATP6V0A4

    ATP6V0A4 - AR Distal Renal Tubular Acidosis

    Kidney disorder characterized by impaired acid secretion in the distal tubules of the kidneys. It leads to an inability to properly excrete acid from the body, resulting in an accumulation of acid and a decrease in blood pH. Common symptoms include metabolic acidosis, electrolyte imbalances, such as low potassium levels, and impaired growth in children.

    Subunit - V0c

    Subunit - V0c

    Subunit - V0c

    Illustration of  v-ATPase complex highlighting the subunit ATP6V0C

    ATP6V0C - AD Developmental and epileptic encephalopathy

    Neurodevelopmental disorder characterized by a combination of developmental delays and frequent seizures. Symptoms often emerge in early infancy or childhood and are associated with significant cognitive and neurological impairments.

    Subunit - V0d

    Subunit - V0c

    Subunit - V0c

    Illustration of  v-ATPase complex highlighting the subunit ATP6V0D2

    ATP6V0D2 - AR Skin and Joint Laxity

    Skin and joint laxity refers to a condition characterized by looseness or excessive elasticity of the skin and joints. Individuals with skin and joint laxity may experience hypermobile joints, increased joint flexibility, and fragile or stretchy skin that is prone to bruising and tearing.

    Subunit - V1A

    Subunit - V1A

    Subunit - V1A

    Illustration of  v-ATPase complex highlighting the subunit ATP6V1A

    ATP6V1A - AD/AR Developmental and epileptic encephalopathy and AR Cutis Laxa (Type IID)

    Potential combination of neurodevelopment delays, cognitive impairments and epilepsy with loose and sagging skin with reduced elasticity.

    Subunit - V1B

    Subunit - V1A

    Subunit - V1A

    Illustration of  v-ATPase complex highlighting the subunit ATP6V1B1

    ATP6V1B1 - AR Renal Tubular Acidosis with Deafness

    Rare kidney disorder that prevents the body from getting rid of excess acid. This can lead to a buildup of acid in the blood, which can cause a variety of health problems, including bone disease, kidney stones, and muscle weakness. Often individuals with this autosomal recessive condition experience severe hearing loss in childhood or young adulthood.

    Subunit - V1A

    Subunit - V1C

    Illustration of  v-ATPase complex highlighting the subunit ATP6V1B2

    ATP6V1B2 - Several conditions described:

    AD Dominant Deafness-Onychodystrophy Syndrome (DDOD): Disorder characterized by a combination of hearing loss and small or absent nails on the hands and feet.

    AD Zimmerman- Laband Syndrome: Disorder characterized by a combination of facial, dental, and skeletal abnormalities. It is typically present at birth or becomes apparent in early childhood. The syndrome is characterized by features such as coarse facial appearance, gingival enlargement (enlarged gums), intellectual disability, and abnormalities in the fingers and toes.

    AD DOORS Syndrome: Also known as Deafness, Onychodystrophy, Osteodystrophy, Mental Retardation, and Seizures syndrome, it is characterized by a combination of hearing loss, nail abnormalities, skeletal abnormalities, intellectual disability, and seizures. DOORS syndrome is distinct from Zimmerman-Laband Syndrome as it includes additional features like osteodystrophy (abnormal bone development) and seizures, which are not typically present in Zimmerman-Laband Syndrome.

    Subunit - V1C

    Subunit - V1C

    Illustration of  v-ATPase complex highlighting the subunit ATP6V1C2

    ATP6V1C2 - AR Distal Renal Tubular Acidosis

    Kidney disorder characterized by impaired acid secretion in the distal tubules of the kidneys, leading to an accumulation of acid and a decrease in blood pH. It often presents with symptoms such as metabolic acidosis, electrolyte imbalances, and impaired growth in children. dRTA is different from other forms of renal tubular acidosis as it specifically affects the distal tubules of the kidneys, resulting in a distinct pattern of acid-base imbalances.

    Subunit - V1E

    ATP6V1E1 - AR Cutis Laxa (Type IIC)

    Genetic disorder characterized by loose and sagging skin with reduced elasticity and marked facial features.

    Subunit - V1H

    ATP6V1H - AD Short Stature and Osteoporosis

    Condition characterized by both reduced height and decreased bone density. Individuals with short stature and osteoporosis may be at a higher risk of fractures and may require specific interventions to address their bone health.

    Alterations in Subunits V0c'' (ATP6V0B), V0d (ATP6V0D1), V0e (ATP6V0E1 & ATP6V0E2), V1D (ATP6V1D), V1E (ATP6V1E2), V1F (ATP6V1F), and V1G (ATP6V1G1, ATP6V1G2 and ATP6V1G3) have not been reported as associated with human disease.

    (as of June 2023)

    v-ATPase structure, Function and Regulation
    Donate

    We need to go faster

    Consider support our efforts!

     We'll continue working tirelessly to serve our community and advance v-ATPase research.


    Your support is vital to keep us going. Thank you

    Consider support our efforts!

    Consider support our efforts!

    Donate to v-ATPase Alliance to fund research, treatments, and community support. 

    Donate

    Copyright © 2025 v-ATPase Alliance - All rights reserved.


    We are a REGISTERED 501(C)(3) NONPROFIT organization.

    • Home
    • Privacy Policy

    Powered by

    This website uses cookies.

    We use cookies to analyze website traffic and optimize your website experience. By accepting our use of cookies, your data will be aggregated with all other user data.

    DeclineAccept