The HGD gene helps your body break down part of the amino acids tyrosine and phenylalanine. If both copies do not work well, a substance called homogentisic acid builds up and can cause alkaptonuria. This can make urine turn dark after standing and, over time, may lead to pigment buildup in cartilage and other tissues, with joint or spine pain, kidney stones, or heart valve problems. Knowing what this gene does can make it easier to understand why these changes happen.
What is a gene?
Genes are sections of DNA that carry instructions your cells use to make molecules or regulate activities in the body. Some provide the code for proteins, which do the day to day work inside cells. Others are used mainly to guide when a process happens, where it happens, and how active it is. Taken together, genes affect how your body develops and functions, and they can also influence how you respond to food, stress, and medications. For a more detailed explanation of this topic, you can find more in the LearnHub.
Overview
HGDGene function
What if the gene works
The HGD gene helps your body break down parts of the amino acids tyrosine and phenylalanine. Its protein clears homogentisic acid so it does not build up.
Risk
What if the gene does not work
Variants in the HGD gene can cause alkaptonuria, where homogentisic acid builds up. This may darken urine and later lead to joint pain and tissue pigment changes. Milder or more severe variants can affect onset and severity.
Treatment
What does that mean for your treatment
For people with pathogenic or loss-of-function variants in the HGD gene, nitisinone is an established treatment that can shape long-term care. It lowers the chemical that builds up in the body and can slow later complications. Because nitisinone can raise tyrosine levels, treatment usually includes monitoring and sometimes diet changes to reduce eye or skin side effects.
Conditions associated with HGD
Gene function
What if the gene works
Your body constantly breaks down parts of protein from food and old body proteins. The HGD gene supports one middle step in that process. Its protein helps turn a natural breakdown product into the next substance so the pathway can continue. This helps explain what the HGD gene does in the body each day.
Your cells use the HGD gene to help process parts of the amino acids tyrosine and phenylalanine, which come from protein in food and your own tissues. This keeps the breakdown pathway moving in an orderly way.
The HGD gene makes an enzyme, a protein that carries out a chemical step, which changes a substance called homogentisic acid into the next substance in the pathway. That step lets your cells keep handling these natural byproducts normally.
By helping complete this protein processing pathway, the HGD gene supports normal chemical balance during everyday cell activity. It helps your body turn amino acid leftovers into forms that can be used in later steps or cleared.
What is a variant?
A genetic variant is a minor difference in the DNA sequence within a gene. These differences are common and help shape normal human diversity, including differences in appearance, metabolism, and the way the body responds to environmental influences. Many variants do not have any noticeable effect and are simply part of natural genetic variation. Sometimes, however, a variant changes how a gene works more substantially and can contribute to or lead to a genetic condition.
Genetic variants
What if the gene does not work
In discussions of how HGD gene variants affect enzyme activity, most changes make the enzyme less stable, less active, or unable to fold into its usual shape. More disruptive variants can leave little or no working enzyme, while milder variants may allow some activity to remain. This loss of activity lets homogentisic acid build up in the body and, in alkaptonuria, can contribute to earlier onset or more marked features in some people.
How variants are linked to conditions
Pathogenic variants in the HGD gene cause alkaptonuria, a rare inherited condition in which urine may darken and, over time, pigment can build up in joints and other tissues. In most people, alkaptonuria appears when a person inherits two disease-causing HGD variants, one from each parent. Genetic testing can confirm the diagnosis when HGD gene variants are linked to alkaptonuria in a family.
A variant is not necessarily a diagnosis
Genetic variants are a routine part of human biology and are widely found in the general population. Most do not have a direct effect on health and simply reflect natural human diversity. In many genes, carrying a variant associated with a condition indicates a possible link rather than a confirmed diagnosis, especially when several genes and environmental factors are involved. In some situations, though, a single well characterized variant in a particular gene can be enough to confirm the diagnosis.
Are there things that can increase or change my risk?
For HGD, the main factor that changes risk is inheritance: alkaptonuria usually happens only when someone inherits two changed copies of the HGD gene, one from each parent. Risk is higher when both parents are carriers, and it can also be higher in families or communities where the same HGD change is more common.
Inheritance of HGD variants
Variants in the HGD gene are inherited in an autosomal recessive pattern, which is the inheritance pattern for HGD-related alkaptonuria. This means a person usually inherits one changed copy of the HGD gene from each parent. Parents who each carry one variant often do not have symptoms, but with each pregnancy they have a 25% chance of having a child with alkaptonuria, a 50% chance of having a child who is a carrier, and a 25% chance of having a child with two typical copies. In families asking how HGD variants are inherited, sons and daughters are affected equally.
What does my HGD result mean for my family?
For HGD, family members can also carry the same gene change even if they feel completely well. Brothers and sisters may have the condition or be carriers, so relatives may want to discuss whether family testing would be useful. Children of someone with alkaptonuria usually inherit one changed HGD copy and are carriers, and the chance of an affected child depends on whether the other parent also carries an HGD change.
Genetic information
Genetic testing
How you find out about variants
Genetic testing for HGD variants usually uses a blood or saliva sample to read the HGD gene and look for changes linked to alkaptonuria. This can confirm whether a person carries two disease-causing variants or is a carrier with one. Results are interpreted alongside symptoms and family history.
When should I consider getting a genetic test?
Consider HGD testing if you or your child has signs of alkaptonuria, such as urine that turns dark after standing, early joint problems, or a known family history of this condition. Testing can help confirm the cause and clarify whether close relatives may also carry the gene change.
A genetic result is only one part of your health story
A genetic result may provide valuable information, but how much it reveals varies by the condition and the specific type of variant. Over time, many factors, including lifestyle, environment, age, and medical history, influence how the body functions. In some conditions, especially those affected by many genes, genetic information provides context rather than certainty and is most useful when viewed together with other parts of care. In other situations, a genetic result can offer a clear answer. In areas like medication response, genetic results can help put individual experiences in perspective.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. Some people break down or move a drug through the body differently, so the same treatment may work better for one person, seem weaker for another, or cause more side effects in someone else. These differences are common and can influence how strongly a medicine works, how long it lasts, and how sensitive a person is to it.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences can shape a person’s response to medicines. It looks at 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 affect both how strongly a drug works and how the body handles it. This information can support more informed and more individualized treatment decisions. You can read more about this topic in the LearnHub.
Drugs influenced by the HGD 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 adjusted. If you have concerns about side effects, a medicine not working as expected, or possible interactions, it is best to discuss them with your doctor or pharmacist.
History
HGD has an important place in medical history because changes in this gene are linked to alkaptonuria, one of the first conditions used to show that inherited traits can affect the body’s chemistry. In 1902, physician Archibald Garrod described alkaptonuria as an “inborn error of metabolism,” a landmark idea in early genetics and medicine. At that time, doctors recognized the striking darkening of urine long before the gene itself was known. From these first observations, research expanded steadily. Later studies mapped the condition to the HGD gene and confirmed the inherited pattern Garrod had proposed. This work helped shape modern thinking about how single gene variants can lead to specific health conditions.