The HPGD gene gives your body instructions for breaking down prostaglandins, which are hormone-like signals that help control inflammation, blood flow, and the opening of certain blood vessels. This gene helps your body keep those signals from staying too active for too long. If the HPGD gene does not work properly, prostaglandin levels can rise and may lead to finger clubbing, joint and bone changes, thickened skin, or in some babies a heart vessel that stays open after birth.
What is a gene?
Genes are sections of DNA that carry instructions your cells use to make molecules or regulate processes in the body. Some genes hold the instructions for making proteins, the parts of cells that do the work. Others mainly direct when certain processes happen, where they happen, and how active they are. Together, genes influence how the body develops and functions, and they can also affect how you respond to food, stress, or medications. If you want to go into this topic in more detail, you can find more in the LearnHub.
Overview
HPGDGene function
What if the gene works
The HPGD gene helps your body break down prostaglandins, which are short-lived chemical signals. This helps keep inflammation, blood flow, and tissue growth more balanced.
Risk
What if the gene does not work
Variants in the HPGD gene can raise prostaglandin levels, body chemicals that help control inflammation. More disruptive variants are linked to primary hypertrophic osteoarthropathy, with clubbing, joint swelling, and thickened skin that can range from mild to more marked.
Treatment
What does that mean for your treatment
No treatment or management approach specifically tied to pathogenic variants in the HPGD gene is currently established in clinical guidelines. The HPGD gene is also being studied as a biomarker and possible drug target in some cancers because reduced HPGD activity can increase prostaglandin signaling.
Conditions associated with HPGD
Gene function
What if the gene works
Your cells use the HPGD gene to help switch off certain short lived chemical messages called prostaglandins. These messages help coordinate everyday processes such as inflammation, blood flow, and tissue responses. Understanding how the HPGD gene helps control prostaglandin levels in the body makes its role easier to see.
The HPGD gene helps your cells turn active prostaglandins into weaker forms after they deliver a message. This keeps these signals from lasting longer than needed.
By breaking down used prostaglandins, the HPGD gene helps keep their levels in a healthy range. That supports more controlled signaling across many tissues.
This gene supports normal body responses that rely on short prostaglandin signals, including inflammation, blood flow, and tissue repair. It helps these responses stay timely and balanced.
What is a variant?
A genetic variant is a small difference in the DNA sequence of a gene. These differences are common and help shape normal human diversity, including variations in appearance, metabolism, and how the body responds to environmental influences. Many have no noticeable effect and simply represent natural genetic variation. In some situations, though, a variant changes how a gene functions more substantially and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the HPGD gene can change the shape or stability of its enzyme, so it breaks down prostaglandins less effectively. How HPGD gene variants affect protein function depends on the change: some variants leave partial activity, while more disruptive variants can shorten the enzyme or prevent it from working at all. This can lead to a larger rise in prostaglandin signaling, and variants with very little or no enzyme activity may be linked to earlier or more marked HPGD related features.
How variants are linked to conditions
Pathogenic variants in the HPGD gene can cause primary hypertrophic osteoarthropathy, a rare inherited condition that may lead to clubbing of the fingers or toes, joint pain, and extra bone growth. In some families, HPGD gene variants and primary hypertrophic osteoarthropathy also include thickened skin and delayed closure of the ductus arteriosus, a blood vessel that normally closes after birth. This link is well established, and having two disease-causing variants can confirm the diagnosis.
A variant is not necessarily a diagnosis
Genetic variants are a normal part of being human and are common across the general population. Most do not have a direct effect on health and simply reflect natural human diversity. For many genes, carrying a variant associated with a condition suggests a possible link rather than a definite diagnosis, especially when several genes and environmental factors are involved. In some cases, though, a single well-characterized variant in a specific gene is enough to confirm a diagnosis.
Are there things that can increase or change my risk?
There is not yet broadly confirmed evidence on specific factors that increase or reduce health risks related to the HPGD gene. For many living with an HPGD change, risk depends mainly on the exact gene change and whether it is inherited from one or both parents.
Inheritance of HPGD variants
HPGD-related conditions are usually inherited in an autosomal recessive pattern. In practical terms, HPGD gene inheritance means a person typically develops the condition only if they inherit one nonworking copy from each parent. Parents who each carry one HPGD variant are often unaffected, and with each pregnancy there is a 25% chance the child will inherit both variants, a 50% chance the child will be a carrier, and a 25% chance the child will inherit neither variant. This pattern applies to the well-established conditions linked to the HPGD gene.
What does my HPGD result mean for my family?
For families with an HPGD-related condition, close relatives may also carry the same gene change even if they do not have symptoms. Brothers and sisters can sometimes be affected, and parents are often healthy carriers. Other relatives may wish to learn whether they are carriers too, especially when planning a pregnancy.
Genetic information
Genetic testing
How you find out about variants
For people looking into HPGD genetic testing for inherited variants, a lab usually uses a blood or saliva sample to read the HPGD gene’s DNA sequence and sometimes look for missing or extra pieces. Results can show whether you carry a variant, have two variants, or did not inherit the family variant.
When should I consider getting a genetic test?
Consider HPGD genetic testing if someone has unexplained finger or toe clubbing, painful swollen joints, thickened skin, or unusual bone growth, especially when these signs start in childhood or run in the family. Testing can help confirm a rare inherited condition linked to this gene.
A genetic result is only one part of your health story
Genetic test results can be informative, but how much they explain varies by the condition and the specific type of variant. Many other factors also shape how the body functions over time, including lifestyle, environment, age, and medical history. For some conditions, especially those influenced by many genes, genetic information offers context rather than certainty and is most useful when considered alongside other parts of care. In other situations, a genetic result may give a clear answer. In areas such as medication response, genetic results can also help make personal experiences easier to understand.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. Small differences in genes can change how the body breaks down a drug, moves it through the bloodstream, or responds to it at its target. This helps explain why the same medication works well for one person, works less well for another, or causes more side effects in some people.
What is Pharmacogenetics?
Pharmacogenetics is the area of study focused on how genetic differences affect a person’s response to medications. By examining links between genes and drugs, it helps explain why the same treatment can work differently from one person to another. For many medicines, genes can influence how strongly a drug works or how the body processes it. This understanding can support treatment decisions that are more informed and more individualized. You can read more about this topic in the LearnHub.
Drugs influenced by the HPGD gene
When should I seek medical advice?
There isn't yet a broadly confirmed role for this gene in guiding medication choices, so general questions about medicines, side effects, or treatment changes are best discussed with your doctor.
History
Research on the HPGD gene grew out of decades of work on prostaglandins, a group of body signals first studied in the 1930s. In recent decades, awareness of this gene’s role has grown as scientists linked it to the main enzyme that breaks down these signals. Once considered rare, now recognized as an important part of human genetics, changes in the HPGD gene were later tied to inherited forms of digital clubbing and primary hypertrophic osteoarthropathy. Building on this early work, scientists uncovered more about the gene through families in whom several relatives shared the same pattern of bone and skin changes. These findings helped connect older bedside observations with modern genetic testing and clearer diagnosis.