The HARS2 gene helps mitochondria, the parts of cells that make energy, build proteins needed for normal cell function. If this gene does not work properly in both copies, some cells may struggle to make enough energy, especially in the inner ear and ovaries. This is linked to Perrault syndrome, which often causes hearing loss in both males and females and reduced or absent ovarian function in females. Some people may also have balance problems, nerve symptoms, or movement changes.
What is a gene?
Genes are sections of DNA that give your cells instructions for making molecules or regulating processes in the body. Some genes carry the information needed to produce proteins, the parts of cells that do the work. Others mainly control when certain processes happen, where they happen, and how active they are. Together, genes affect how the body develops and works, and they can also influence how you respond to food, stress, or medications. To explore this topic in more detail, you can learn more in the LearnHub.
Overview
HARS2Gene function
What if the gene works
The HARS2 gene helps mitochondria, the cell’s energy makers, build proteins by attaching histidine to a carrier molecule used in protein assembly. This supports normal energy production, especially in tissues with high energy needs.
Risk
What if the gene does not work
Variants in the HARS2 gene can cause Perrault syndrome, usually with hearing loss and, in many females, ovarian insufficiency. Effects range from milder to more severe, which can influence when symptoms begin and whether neurologic features also appear.
Treatment
What does that mean for your treatment
No treatment or drug choice approach specific to the HARS2 gene is currently established in clinical guidelines. Care is guided by a person's symptoms, such as hearing support or treatment for ovarian insufficiency, rather than by the HARS2 variant itself.
Conditions associated with HARS2
Gene function
What if the gene works
Your cells need a steady energy supply. The HARS2 gene helps make that possible inside mitochondria, the parts of cells that produce energy. Understanding what the HARS2 gene does helps explain how mitochondria build the proteins they need for daily cell work. When this gene is working properly, it supports accurate protein making in mitochondria.
Inside mitochondria, the HARS2 gene helps attach the amino acid histidine to a transfer RNA, a small molecule that brings building blocks to the protein making machinery. This matching step helps the right amino acid get placed in growing mitochondrial proteins.
The HARS2 gene supports protein production inside mitochondria. These proteins are essential parts of the cell’s energy making system and help mitochondria carry out their routine work.
By helping mitochondria make key proteins, the HARS2 gene supports steady energy production. This allows cells to keep up with everyday tasks that depend on a reliable supply of energy.
What is a variant?
A genetic variant is a minor difference in a gene’s DNA sequence. Variants are common and are part of normal human diversity, including differences in appearance, metabolism, and how the body responds to environmental influences. Many have no noticeable effect and simply represent natural genetic variation. Sometimes, however, a variant can change 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 HARS2 gene can change the shape or stability of its mitochondrial protein, so it may not properly load histidine onto transfer RNA, a helper molecule used to build proteins. This explains how HARS2 gene variants affect cells at a basic level. Some variants leave part of the protein working, while more disruptive variants can sharply reduce activity. In Perrault syndrome, lower remaining activity may be linked to earlier or more marked hearing loss and, in some females, ovarian involvement.
How variants are linked to conditions
Pathogenic variants in the HARS2 gene cause Perrault syndrome type 2, an inherited condition that usually appears when both copies of the gene carry a pathogenic variant. It is linked to hearing loss and, in many females, reduced ovarian function that may affect puberty, menstrual periods, or fertility. Males with variants in the HARS2 gene usually have hearing loss without ovarian features. These HARS2 gene variants linked to hearing loss are most often found in people with Perrault syndrome.
A variant is not necessarily a diagnosis
Genetic variants are a common and normal feature of human biology. Most do not directly affect health and instead reflect natural variation among people. For many genes, having a variant associated with a condition points to a possible link rather than a certain diagnosis, particularly when several genes and environmental factors play a part. In some situations, though, one well-characterized variant in a particular gene is enough to confirm a diagnosis.
Are there things that can increase or change my risk?
For HARS2, risk is mainly linked to inheriting harmful changes in both copies of the gene, rather than to lifestyle or everyday exposures. There is not broadly confirmed evidence that specific habits or environmental factors clearly increase or lower HARS2-related risk, so anyone concerned about personal or family risk should speak with a doctor or genetic counselor.
Inheritance of HARS2 variants
HARS2-related conditions usually follow an autosomal recessive inheritance pattern. This means a person inherits one HARS2 variant from each parent, and the condition appears when both copies of the HARS2 gene are affected. Parents who each carry one variant are often unaffected carriers, and with each pregnancy they have a 25% chance of having an affected child, a 50% chance of having a child who is a carrier, and a 25% chance of having a child with no familial variant. Because the HARS2 gene is on an autosome, this pattern is the same for sons and daughters.
What does my HARS2 result mean for my family?
For families with a disease-causing change in the HARS2 gene, close relatives may also carry the same change, especially brothers and sisters. Parents are often healthy carriers, and other relatives may be carriers too. If both parents carry a HARS2 change, each child has a chance to be born with the condition, so the result can matter for future pregnancies as well.
Genetic information
Genetic testing
How you find out about variants
To find out about variants in the HARS2 gene, genetic testing reads DNA from a blood or saliva sample and looks for changes in the HARS2 gene. Results may show a disease causing variant, a benign variant, or an unclear finding, and they can help clarify diagnosis but cannot predict exactly how features may vary.
When should I consider getting a genetic test?
Genetic testing for HARS2 may be worth discussing if there is early hearing loss, especially when it runs in the family or happens with delayed puberty, missing periods, or ovaries stopping work too early in girls or women. It can also help clarify the cause when Perrault syndrome is suspected.
A genetic result is only one part of your health story
Genetic test results can provide useful insight, but how much they reveal varies depending on the condition and the type of variant identified. Many factors also shape how the body works over time, including lifestyle, environment, age, and medical history. For some conditions, especially those influenced by many genes, genetic information provides context rather than certainty and is best understood as part of the broader picture of care. In other situations, a genetic result can offer a clear answer. In areas such as medication response, genetic findings 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. Some people break down a drug more slowly or more quickly, while others may be more or less sensitive to its effects. This helps explain why the same treatment can work well for one person, seem less effective for another, or cause more side effects in someone else.
What is Pharmacogenetics?
Pharmacogenetics examines how differences in genes shape the way a person responds to medications. It looks at the relationship between genes and drugs to help explain why the same treatment may work differently from one person to another. For many medicines, genes affect both how strongly a drug works and how the body handles it. This information can support treatment decisions that are more informed and more individualized. To explore this topic further, you can find more information in the LearnHub.
Drugs influenced by the HARS2 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding how medicines are chosen or used, so general medication questions, side effects, or other health concerns are best discussed with your doctor.