Your cells depend on the FH gene to help turn food into usable energy and keep a natural chemical called fumarate from building up. If this gene does not work properly, cells can become stressed, which may cause a rare condition with severe brain and developmental problems or, in other people, increase the chance of noncancerous skin and uterine growths and a form of kidney cancer. In medicine, the FH gene is important because certain variants are linked to hereditary leiomyomatosis and renal cell cancer.
What is a gene?
A gene is a stretch of DNA that carries instructions your cells use to make molecules or regulate activities in the body. Some genes provide the directions for producing proteins, which are the functional parts of cells. Others mainly guide when, where, and how strongly certain processes take place. Taken together, genes affect how the body develops and functions, and they can influence how you respond to food, stress, or medications. For a deeper look at this subject, you can find more information in the LearnHub.
Overview
FHGene function
What if the gene works
The FH gene helps cells make energy through a key step in the cell’s energy cycle. This supports normal cell growth and day to day function.
Risk
What if the gene does not work
Different variants in the FH gene can cause fumarate hydratase deficiency, with neurologic symptoms ranging from milder to severe, or hereditary leiomyomatosis and renal cell cancer, involving skin bumps, uterine fibroids, and kidney cancer risk.
Treatment
What does that mean for your treatment
Pathogenic variants in the FH gene can change treatment for FH associated kidney tumors: doctors usually favor prompt surgery instead of watchful monitoring for a small mass, because these tumors may spread early. For advanced FH associated kidney cancer, bevacizumab plus erlotinib is a guideline recognized treatment option.
Conditions associated with FH
Gene function
What if the gene works
Your cells need a steady way to turn food into usable energy all day long. The FH gene supports this basic process by helping one step of the cell’s main energy pathway run smoothly. Understanding what the FH gene does helps explain how cells keep their energy system balanced.
Inside your cells, the FH gene helps change fumarate into malate during the citric acid cycle, a key energy-making pathway. This step helps your body draw usable energy from carbohydrates, fats, and proteins.
By moving this reaction forward, the FH gene helps the cell’s energy cycle keep turning smoothly. That steady flow supports routine work in cells that need reliable energy throughout the day.
The FH gene also helps keep fumarate levels in a healthy range inside cells. This supports a balanced chemical environment and helps cells handle nutrients in an orderly way.
What is a variant?
A genetic variant is a small change in the DNA sequence within a gene. These changes are common and are part of normal human diversity, including differences in appearance, metabolism, and how the body responds to environmental influences. Many variants do not cause any noticeable effect and simply reflect natural genetic variation. In some situations, though, a variant can more substantially change how a gene functions and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Changes in the FH gene often alter the protein's shape, stability, or ability to join with matching copies, which helps explain how FH gene variants affect enzyme activity. Some variants only partly reduce its work, while more severe variants can leave little or no working enzyme. In FH-related conditions, larger drops in activity are often linked to earlier onset or more pronounced features.
How variants are linked to conditions
Pathogenic variants in the FH gene are best known for causing hereditary leiomyomatosis and renal cell cancer, a condition linked to skin leiomyomas, early or multiple uterine fibroids, and an increased risk of kidney cancer. A more disruptive variant in both copies of the FH gene can cause fumarate hydratase deficiency, a rare inherited condition that affects brain development and movement. These are the main FH gene conditions supported by broad medical consensus.
A variant is not necessarily a diagnosis
Genetic variants are a usual part of human biology and are widespread in the general population. Most do not have a direct effect on health and simply represent natural variation among people. For many genes, carrying a variant associated with a condition indicates a possible link rather than a confirmed diagnosis, especially when more than one gene and environmental factors are involved. In some situations, though, a single well understood variant in a specific gene can be enough to confirm a diagnosis.
Are there things that can increase or change my risk?
For people with an inherited change in the FH gene, the gene change itself is the main driver of risk, especially for related kidney cancer and smooth muscle growths. There is not enough evidence to say that diet, exercise, or other lifestyle changes lower this inherited risk, so regular monitoring and early attention to new symptoms are most important.
Inheritance of FH variants
The inheritance of the FH gene variants depends on the condition involved. For hereditary leiomyomatosis and renal cell cancer, variants in the FH gene are inherited in an autosomal dominant pattern, so a parent with the variant can pass it to each child with a 50% chance. A different FH related condition, fumarase deficiency, follows an autosomal recessive pattern, which means a child must inherit one altered copy from each parent. Because of this, who can inherit FH related conditions and the chance of passing them on are not the same in every family.
What does my FH result mean for my family?
FH results can have different meanings for relatives because this gene is linked to two well-known inherited conditions. For the adult cancer-risk condition tied to FH, close family members may also carry the same gene change and may want to discuss testing. For the rarer childhood condition caused by FH, relatives may be healthy carriers, especially brothers, sisters, or future parents in the family. The family impact depends on which FH result or condition is present.
Genetic information
Genetic testing
How you find out about variants
FH gene genetic testing usually uses a blood or saliva sample to look for variants in the FH gene. A lab reads the DNA code and checks whether any changes match known pathogenic, likely benign, or uncertain variants. Results can show whether you carry an FH variant and may help guide family testing.
When should I consider getting a genetic test?
Consider FH genetic testing if you or close relatives have had kidney cancer at a young age, many uterine fibroids, or firm, sometimes painful skin bumps. Testing can also matter when these features run in a family, because some FH changes can greatly raise the risk of kidney cancer.
A genetic result is only one part of your health story
A genetic finding can provide useful insight, but how much it explains depends on the condition and on the kind of variant involved. Factors such as lifestyle, environment, age, and medical history also shape how the body works over time. For some conditions, especially those influenced by many genes, genetic information offers context rather than certainty and is most helpful when considered alongside other parts of care. In other situations, a genetic result can give a clear answer. In areas like medication response, genetic results may help place personal experiences in context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how your body handles certain medicines, so the same treatment may work well for one person and less well for another. Some people break down a drug more quickly, while others process it more slowly or are more sensitive to its effects. These differences are common and can influence how much benefit a medicine gives or the chance of side effects.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences can shape a person’s response to medicines. It focuses on patterns between genes and drugs to help explain why the same treatment may work differently from one person to another. For many medications, genes influence either how the body handles a drug or how strong its effects are. This information can support more informed, individualized treatment decisions. To explore this subject in greater detail, you can learn more in the LearnHub.
Drugs influenced by the FH gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding everyday medication choices, so general health concerns or questions about medicines are best discussed with your doctor. FH has been studied in certain FH-related kidney cancers to understand response to some cancer treatments, but this remains specialist cancer care rather than routine gene-guided prescribing.
History
The FH gene entered medical history through studies of fumarase, an enzyme identified in the early 20th century during work that mapped the body’s core energy pathways. Scientists later connected the human FH gene to inherited illness, marking an important step in linking metabolism with genetics. From these first observations, research expanded steadily. In 2002, pathogenic variants in the FH gene were tied to hereditary leiomyomatosis and renal cell cancer, a finding that helped explain why some families developed both skin or uterine leiomyomas and kidney cancer. That discovery also helped launch broader interest in “oncometabolites,” small molecules that can drive cancer growth. Since then, FH has remained an important gene in cancer genetics and inherited kidney cancer research.