The FGF23 gene plays an important role in balancing phosphate and vitamin D, which support healthy bones and teeth. If it does not work properly, phosphate levels can become too high or too low, which may lead to soft or weak bones, bone pain, fractures, kidney problems, or mineral deposits in soft tissues. Some variants in the FGF23 gene are linked to inherited conditions with low phosphate and poor bone hardening. Other variants raise phosphate levels instead, so effects depend on the specific variant.
What is a gene?
Genes are stretches of DNA that give your cells information they can use to make molecules or manage processes in the body. Some genes hold the directions for producing proteins, the parts of cells that do the work. Other genes mainly regulate when certain processes happen, where they happen, and how active they are. Together, genes affect how the body develops and functions, and they can shape how you respond to food, stress, or medications. For a more in depth look at this topic, you can find more in the LearnHub.
Overview
FGF23Gene function
What if the gene works
The FGF23 gene helps control phosphate levels in the blood by signaling the kidneys to release extra phosphate. It also lowers active vitamin D when needed, which supports balanced mineral levels for bones and teeth.
Risk
What if the gene does not work
Variants in the FGF23 gene can cause either low phosphate bone disease, including rickets or osteomalacia, or high phosphate with soft tissue calcium deposits. Milder or more severe variants may affect when symptoms start and which features appear.
Treatment
What does that mean for your treatment
For pathogenic loss-of-function variants in the FGF23 gene, treatment usually focuses on lowering high phosphate, often with a low-phosphate diet, phosphate binders, and sometimes acetazolamide. Drug choices are guided by phosphate levels and symptoms rather than by the exact variant. No approved therapy currently replaces FGF23.
Conditions associated with FGF23
Gene function
What if the gene works
Your body uses the FGF23 gene to keep key minerals in balance. It is especially important for phosphate control and for setting how much active vitamin D is available. When this system works well, the kidneys, bones, and gut stay coordinated so mineral levels remain in a healthy range.
The FGF23 gene helps control phosphate levels in the blood. It signals the kidneys to release extra phosphate into urine, which keeps everyday mineral balance steadier.
This gene also helps set how much active vitamin D your body makes. That shapes how much phosphate and calcium your gut absorbs from food.
Bone cells use the FGF23 gene to send mineral balance messages to the kidneys. This helps match kidney handling of phosphate to your body’s ongoing needs.
What is a variant?
A genetic variant is a small difference in the DNA sequence of a gene. These changes are common and are part of normal human diversity, including differences in appearance, metabolism, or how the body responds to environmental influences. Many variants do not have any noticeable effect and simply represent natural genetic variation. In some situations, though, a variant can change 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 FGF23 gene can change how much active FGF23 protein is made, how well it folds, and how easily it is broken down. Some make the protein unusually resistant to cutting, so active protein stays in the body longer, while others reduce stability, release, or activity. This range helps explain how FGF23 gene variants affect function: milder variants may partly alter activity, while more severe variants can shift phosphate control enough to bring earlier or stronger signs.
How variants are linked to conditions
When doctors discuss FGF23 gene variants and related conditions, the best established links are with two rare inherited conditions. Pathogenic variants in the FGF23 gene can cause autosomal dominant hypophosphatemic rickets, which may lead to soft or painful bones, bowed legs, and short stature. Other rare variants cause hyperphosphatemic familial tumoral calcinosis, marked by high phosphate levels and calcium deposits in soft tissues.
A variant is not necessarily a diagnosis
Genetic 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 instead reflect normal human diversity. For many genes, carrying a variant associated with a condition suggests a possible link rather than a confirmed diagnosis, especially when several genes and environmental factors play a role. In some situations, 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?
For FGF23, the main factor that changes risk is whether an altered copy of the gene runs in the family, since this can strongly raise the chance of developing low phosphate problems and soft, weak bones. There is not enough evidence to say that diet, exercise, or other lifestyle changes lower the inherited risk.
Inheritance of FGF23 variants
For families trying to understand how FGF23 gene variants are inherited, the pattern depends on the specific FGF23-related condition. Some FGF23 changes are passed down in an autosomal dominant way, which means one altered copy from either parent can be enough for a child to inherit the condition. Other FGF23 changes follow an autosomal recessive pattern, which means a child usually inherits one altered copy from each parent. In either pattern, mothers and fathers can pass FGF23 variants to sons or daughters.
What does my FGF23 result mean for my family?
A disease-causing change in the FGF23 gene is linked to a condition called autosomal dominant hypophosphatemic rickets, which means close relatives can also carry the same change. Parents, brothers, sisters, and children may want to learn whether the result is present in them too, especially if they have bone pain, frequent fractures, bowed legs, or dental problems. The exact family impact depends on whether the result is clearly disease-causing.
Genetic information
Genetic testing
How you find out about variants
Genetic testing for variants in the FGF23 gene looks for DNA changes linked to phosphate balance conditions. A lab reads the gene from a blood sample, saliva sample, or cheek swab and compares it with the usual sequence to see whether a variant is present. Results may show a pathogenic variant, a benign variant, or a variant of uncertain significance.
When should I consider getting a genetic test?
Genetic testing for the FGF23 gene may be considered if someone has ongoing low phosphate levels with weak or soft bones, bone pain, frequent fractures, or rickets, especially when these problems run in the family. It can also help explain rare inherited phosphate conditions and guide testing of relatives.
A genetic result is only one part of your health story
Genetic test results can provide useful insight, but how much they reveal depends on the condition and on the kind of variant involved. How the body works over time is also shaped by many other factors, 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 helpful when considered alongside other parts of care. In other situations, a genetic result can give a clear answer. In areas such as medication response, genetic findings may also help place personal experiences into context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. Small differences in DNA can change how the body absorbs, breaks down, transports, or responds to a drug. This is common and helps explain why the same treatment works well for one person but less well for another, or why some people are more likely to notice side effects. In some cases, these differences can influence both how effective a medicine is and how sensitive a person may be to it.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences affect the way people respond to medicines. It looks at gene and drug patterns to understand why the same treatment may work differently from one person to another. For many medications, genes can influence both how strongly a drug works and how the body handles it. This information can support more informed, individualized treatment choices. More on this topic is available in the LearnHub.
Drugs influenced by the FGF23 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in predicting medication response, so general concerns about medicines, side effects, or changes in your health are best discussed with your doctor.
History
In 2000, researchers identified the FGF23 gene while studying families with autosomal dominant hypophosphatemic rickets, a milestone that clarified a long-standing puzzle in phosphate-related bone disease. Soon after, the same gene was linked to tumor-induced osteomalacia, connecting rare inherited and acquired conditions through one genetic pathway. Building on this early work, scientists showed that FGF23 had a central role in modern understanding of phosphate balance and vitamin D regulation. These discoveries reshaped how clinicians classified several low-phosphate conditions. Over time, descriptions became more precise as blood testing for FGF23 entered research and specialist care. Today, the history of the FGF23 gene is closely tied to major advances in diagnosing and grouping phosphate-wasting conditions.