The CLPP gene helps mitochondria, the parts of cells that make energy, clear away damaged proteins. If the CLPP gene does not work properly, these proteins can build up and cells may struggle to make and manage energy, especially in the inner ear, ovaries, and nervous system. Pathogenic variants in the CLPP gene can cause a rare inherited condition called Perrault syndrome, which often involves hearing loss and, in many females, reduced or absent ovarian function. Some people also develop problems with balance, movement, or nerve function.
What is a gene?
Genes are stretches of DNA that carry instructions your cells use to make molecules or regulate activities in the body. Some genes provide the directions for making proteins, which do much of the cell’s work. Other genes mainly guide when certain processes happen, where they happen, and how active they are. Together, genes affect how the body develops and works, and they can influence how you respond to food, stress, or medications. More detailed information on this topic is available in the LearnHub.
Overview
CLPPGene function
What if the gene works
The CLPP gene helps mitochondria, the parts of cells that make energy, break down damaged or extra proteins. This cleanup supports healthy energy production and helps cells keep their internal balance.
Risk
What if the gene does not work
Variants in the CLPP gene can cause Perrault syndrome, often with hearing loss and, in females, reduced ovarian function. Some also have movement problems, and milder or more severe variants can affect when symptoms appear and how marked they are.
Treatment
What does that mean for your treatment
No CLPP-specific treatment or drug choice is currently established for people with a pathogenic loss-of-function variant in the CLPP gene. The CLPP gene is being studied as a drug target in cancer research, including medicines that activate the CLPP protein, but this is not an approved treatment approach for inherited CLPP-related conditions.
Conditions associated with CLPP
Gene function
What if the gene works
Inside each cell, the CLPP gene helps keep mitochondria running smoothly. Mitochondria are the parts of cells that turn food into usable energy. Understanding how the CLPP gene helps mitochondria work can make it easier to see how cells stay balanced during everyday activity.
Inside mitochondria, CLPP helps break down worn out or misfolded proteins. It works as part of a protein disposal system, so old pieces can be cleared away and their building blocks reused.
The CLPP gene works with helper proteins that recognize which mitochondrial proteins need to be unfolded and removed. This quality control helps mitochondria keep a more orderly set of proteins for daily cell activity.
By keeping mitochondrial proteins in good working order, the CLPP gene supports steady energy production. This is a key part of what the CLPP gene does in your cells, especially in tissues that use a lot of energy.
What is a variant?
A genetic variant is a small difference in the DNA sequence of a gene. These differences are common and form part of normal human diversity, such as variation in appearance, metabolism, or the way the body responds to environmental influences. Many variants do not have any noticeable effect and simply represent natural genetic variation. In some situations, however, a variant can affect how a gene works more substantially and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the CLPP gene can change the shape, stability, or assembly of its protein, so cells make less of it or a version that cannot cut damaged proteins inside mitochondria (the parts of cells that make energy). This is how CLPP gene variants affect protein function at a cellular level. Milder variants may leave some activity, while more severe variants can remove it almost completely and are more often linked with earlier or broader features of CLPP-related disease.
How variants are linked to conditions
Pathogenic variants in the CLPP gene are best known for causing Perrault syndrome type 3, a rare inherited condition. The link between CLPP gene variants and Perrault syndrome is well established: affected people usually have sensorineural hearing loss, and people with ovaries may also develop primary ovarian insufficiency. Some also have neurologic features such as balance problems or nerve symptoms.
A variant is not necessarily a diagnosis
Gene variants are a usual part of human biology and are common across the general population. Most do not have a direct effect on health and simply contribute to natural human diversity. For many genes, carrying a variant associated with a condition suggests a possible link rather than a definitive diagnosis, especially when several genes and environmental factors are involved. In some situations, though, a single well-characterized variant in a specific gene can be enough to confirm a diagnosis.
Are there things that can increase or change my risk?
For CLPP, risk is mainly tied to inheritance: people are affected when they inherit two nonworking copies of the gene, one from each parent. A family history of a CLPP-related condition, or parents who are related by blood, can raise the chance of this happening.
Inheritance of CLPP variants
For families learning how CLPP gene variants are inherited, the established pattern for CLPP-related conditions is autosomal recessive. This means a person usually inherits one altered copy of the CLPP gene from each parent. Parents who each carry one CLPP variant are often unaffected themselves, but with each pregnancy there is a 25% chance the child inherits both altered copies, a 50% chance the child is a carrier, and a 25% chance the child inherits neither altered copy. Sons and daughters are affected at the same rate.
What does my CLPP result mean for my family?
For CLPP, family implications are usually discussed in a recessive pattern. This often means parents are healthy carriers, and brothers or sisters may also be affected or be carriers. Other close relatives, such as siblings of the parents, may be carriers too, so the result can matter beyond just one person in the family.
Genetic information
Genetic testing
How you find out about variants
CLPP genetic testing looks for changes in the CLPP gene using a blood sample, saliva, or sometimes cheek cells. A lab reads the gene’s DNA sequence to check for variants, and results may show a disease-causing variant, a benign finding, or a variant of uncertain significance.
When should I consider getting a genetic test?
Testing for changes in the CLPP gene may be worth considering when hearing loss runs in the family, especially if it occurs with delayed or absent puberty, early loss of periods, infertility, balance problems, or nerve symptoms. A confirmed CLPP variant can help explain Perrault syndrome and support family planning decisions.
A genetic result is only one part of your health story
A genetic result can provide useful insight, but how much it can tell you depends on the condition and the specific variant involved. How the body works over time is also shaped by many factors, including lifestyle, environment, age, and medical history. In some conditions, especially those influenced by many genes, genetic information offers context rather than certainty and is best considered alongside other parts of care. In other situations, a genetic result may give a clear answer. In areas like medication response, genetic results can also help put individual experiences into context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. This helps explain why the same treatment works well for one person, has less effect in another, or causes more side effects in someone else. Part of the difference comes from how the body breaks down, moves, or responds to a drug, and inherited gene changes can influence each of these steps. These differences are common and can shape both how well a medicine works and how sensitive a person may be to it.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences affect the way people respond to medications. It focuses on links between genes and drugs to help explain why the same treatment may work differently from one person to another. For many medicines, genes can influence both how strongly a drug works and how the body processes it. This information can help support more informed, personalized treatment decisions. More information on this topic is available in the LearnHub.
Drugs influenced by the CLPP gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding medication choice or dose, so questions about side effects, treatment response, or new symptoms are best discussed with your doctor.
History
CLPP first came to scientists’ attention through studies of bacteria, where related Clp proteins were identified as part of a system that breaks down unwanted proteins. Later, researchers found a human version, the CLPP gene, and recognized that it works in mitochondria, the parts of cells that make energy. Building on this early work, scientists connected pathogenic variants in the CLPP gene to Perrault syndrome in 2013, linking the gene to hearing loss and ovarian insufficiency in some affected women. That discovery gave the gene a clearer place in human genetics. Since then, CLPP has remained mainly of scientific and clinical interest rather than broad public attention. Its history is a good example of how basic laboratory research can lead to answers for families with rare inherited conditions.