The FOLH1 gene helps your body absorb folate from food and also makes the PSMA protein found on some cells, especially in the prostate. If this gene does not work well, folate handling can be affected, and rare inherited variants may be linked to problems with brain development and nerve function. Some people first hear about the FOLH1 gene through PSMA PET scans and targeted prostate cancer treatment, because this gene gives rise to the PSMA marker used in those tests and therapies.
What is a gene?
Genes are stretches of DNA that carry instructions your cells use to make molecules or regulate processes in the body. Some genes provide the information needed to make proteins, the parts of cells that do much of the work. Other genes mainly control when certain processes happen, where they occur, and how active they are. Taken together, genes affect how the body develops and works, and they can influence how you respond to food, stress, or medications. For a deeper look at this topic, you can learn more in the LearnHub.
Overview
FOLH1Gene function
What if the gene works
The FOLH1 gene helps your body absorb folate from food by breaking it into a form the intestine can take up. It also helps regulate signaling between nerve cells in the brain.
Risk
What if the gene does not work
Milder to more severe variants in the FOLH1 gene can reduce how well cells break down dietary folate into an absorbable form and process certain nerve cell signaling molecules. This may weaken folate handling and cell signaling to different degrees.
Treatment
What does that mean for your treatment
For pathogenic or loss-of-function variants in the FOLH1 gene, no gene-specific treatment or drug selection approach is currently established. Separately, the FOLH1 gene product is widely used as a prostate cancer imaging and radioligand therapy target, which reflects tumor expression rather than inherited loss-of-function status.
Gene function
What if the gene works
If you carry the FOLH1 gene, it helps your body with two steady jobs: preparing folate from food for absorption and adjusting certain nerve signals. Its protein sits on the cell surface and cuts specific molecules into usable parts. This is part of how the FOLH1 gene helps absorb folate from food and supports communication between nerve cells.
In the small intestine, the FOLH1 gene helps trim folate from food into a form that can be absorbed more easily. This supports the body’s supply of folate, a B vitamin your cells use to make and maintain DNA.
The protein made from the FOLH1 gene sits on the outer surface of certain cells. There, it cuts small linked pieces from selected molecules so they can be absorbed, recycled, or used in the next step.
In the nervous system, the FOLH1 gene helps break down NAAG (a chemical messenger used by nerve cells). This releases glutamate, another messenger, and helps fine tune communication between nerve cells.
What is a variant?
A genetic variant is a minor change in a gene’s DNA sequence. These changes are common and help shape 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. In some situations, however, a variant can change how a gene functions more significantly and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the FOLH1 gene can affect protein structure and activity by changing key building blocks, shortening the protein, or disrupting how cells read the gene. Some variants make the protein fold poorly, reach the cell surface less efficiently, or work with reduced enzyme activity. Milder changes may leave some function, while more severe variants can lead to very little or no working protein. This range helps explain why the functional impact of FOLH1 gene variants can differ from person to person.
How variants are linked to conditions
Research on FOLH1 gene variants and health conditions is still developing. The FOLH1 gene does not yet have a broadly confirmed link to one specific inherited condition, although studies have explored possible associations in different settings. If you have a reported variant in the FOLH1 gene, your doctor or genetic counselor can explain what that result means in the context of your personal and family history.
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 indicates a possible link rather than a definite diagnosis, especially when multiple genes and environmental factors are involved. In some situations, however, 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 clearly increase or reduce health risk related to the FOLH1 gene. Anyone with concerns about personal or family risk can talk with a doctor or genetic counselor for guidance based on their own history.
Inheritance of FOLH1 variants
When people look into how FOLH1 variants are inherited, the main recognized pattern for FOLH1-related disease is autosomal recessive. This means a person usually inherits one changed copy of the FOLH1 gene from each parent. Parents who each carry one changed copy are often unaffected, and with each pregnancy there is a 25% chance the child inherits both changed copies, a 50% chance the child is a carrier, and a 25% chance the child inherits neither changed copy. Because the FOLH1 gene is on a nonsex chromosome, this pattern is the same for boys and girls.
What does my FOLH1 result mean for my family?
For the rare health conditions linked to FOLH1, the family pattern is usually recessive. This means parents are often healthy carriers, brothers and sisters may also be affected or may carry the gene change without symptoms, and other relatives could be carriers too. This can matter most for family planning, because two carriers can have a child with the condition.
Genetic information
Genetic testing
How you find out about variants
Genetic testing for FOLH1 variants uses a blood, saliva, or cheek swab sample to read the DNA sequence of the FOLH1 gene and look for changes. Results can show whether a variant is present and whether it is currently understood as benign, uncertain, or linked to a health condition.
When should I consider getting a genetic test?
There isn't yet a broadly established reason to get genetic testing just for the FOLH1 gene. Testing decisions are usually based on your personal health history, family history, and the reason testing is being considered, ideally with a doctor or genetic counselor.
A genetic result is only one part of your health story
A genetic finding can provide useful insight, but the amount it reveals depends on the condition and on the kind of variant involved. How the body functions over time is also shaped by many factors, including lifestyle, environment, age, and medical history. For some conditions, particularly those affected by many genes, genetic information offers context rather than certainty and is most helpful when considered with other parts of care. In other situations, a genetic result can give a clear answer. In areas like medication response, genetic results can also help put individual experiences in context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how your body responds to medicines. This helps explain why the same treatment works well for one person, feels too strong for another, or does not help as much as expected. Small differences in genes can change how the body breaks down a drug, moves it through the body, or responds to it at its target, which can influence benefit and side effects.
What is Pharmacogenetics?
Pharmacogenetics is the area of study that looks at how genetic differences affect responses to medications. By examining connections between genes and drugs, it helps explain why the same treatment may work differently from one person to another. With many medicines, genes influence 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. More detail on this topic is available in the LearnHub.
Drugs influenced by the FOLH1 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding medication response, so questions about medicines, side effects, or supplement use are best discussed with your doctor.
History
Researchers first drew major attention to the FOLH1 gene in the late 1980s while studying prostate cancer, when its protein became known as prostate specific membrane antigen, or PSMA. Over time, scientists’ understanding of the gene’s function has changed. It was later linked to earlier work on an enzyme in the small intestine and brain, showing that names from different fields were pointing to the same gene. Scientific classifications changed as researchers learned more about the gene. In the 2000s and 2010s, interest grew sharply because PSMA became central to new prostate cancer scans and targeted treatments. That shift moved the FOLH1 gene from a research finding into everyday clinical use.