The HSD17B3 gene helps the testes make testosterone, a hormone that supports typical male sex development before birth and during puberty. If this gene does not work well, a child with a 46,XY chromosome pattern may be born with genitals that look typically female or are not clearly male or female. Some later develop more masculine physical changes at puberty because the body can make testosterone in other ways. Understanding this gene can help make sense of some differences in sex development and why genetic testing may clarify the cause.
What is a gene?
Genes are stretches of DNA that hold instructions your cells use to make molecules or regulate activities in the body. Some genes provide the code for proteins, which do much of the cell’s work. Others mainly guide when, where, and how strongly certain activities take place. Together, genes affect how the body develops and functions, and they can influence how you respond to food, stress, or medications. For a closer look at this topic, you can find more in the LearnHub.
Overview
HSD17B3Gene function
What if the gene works
The HSD17B3 gene helps the testes make testosterone from a related hormone. This supports typical development of male sex traits before birth and during puberty.
Risk
What if the gene does not work
Changes in the HSD17B3 gene can reduce testosterone production from androstenedione. In people with 46,XY chromosomes, effects can range from female-appearing or ambiguous genitals at birth to more male-typical changes appearing around puberty.
Treatment
What does that mean for your treatment
No HSD17B3-specific treatment or drug selection strategy is currently established. Care is individualized and may include hormone treatment and other supportive management based on a person’s anatomy, puberty, and goals, rather than the HSD17B3 result alone.
Conditions associated with HSD17B3
Gene function
What if the gene works
This gene supports one of the last steps in testosterone production. It is most active in the testes, especially in the cells that make sex hormones. In normal body function, this helps explain how the HSD17B3 gene helps make testosterone and support typical male development before birth and at puberty.
In the testes, the HSD17B3 gene helps turn androstenedione into testosterone. This is a key final step in making the main sex hormone used for typical male development and puberty.
Its protein works mostly in Leydig cells, the hormone making cells of the testes. By changing a weaker hormone precursor into testosterone, it supports normal androgen production before birth and again during puberty.
What is a variant?
A genetic variant is a minor change in the DNA sequence of a gene. These changes are common and help make up normal human diversity, including differences in appearance, metabolism, and how the body responds to environmental influences. Many variants do not have any noticeable effect and simply reflect natural genetic variation. In some cases, though, a variant can change the function of a gene more substantially and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the HSD17B3 gene can reduce or block the enzyme’s activity, so cells make less testosterone from a related hormone precursor. This helps explain how HSD17B3 gene variants affect testosterone production. Milder variants may leave some activity, while more severe variants can leave little or none, which can influence how early and how strongly features of 46,XY sex development differences appear.
How variants are linked to conditions
Pathogenic variants in the HSD17B3 gene cause 17-beta-hydroxysteroid dehydrogenase 3 deficiency, a rare inherited condition affecting sex development in people with a 46,XY chromosome pattern. This condition is part of the group often called 46,XY differences in sex development. People may be identified at birth or later, including around puberty.
A variant is not necessarily a diagnosis
Gene variants are a routine part of human biology and are common across the population. Most do not have a direct effect on health and simply reflect normal 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 contribute. In some situations, though, a single well-characterized variant in a particular gene can be enough to confirm a diagnosis.
Are there things that can increase or change my risk?
For HSD17B3, risk is mostly set by inheritance rather than lifestyle. A child is affected when they inherit two changed copies of the HSD17B3 gene, so risk is higher when both parents are carriers or when close blood relatives have children together. There is not enough evidence to say diet, exercise, or other habits change this genetic risk.
Inheritance of HSD17B3 variants
Variants in the HSD17B3 gene are inherited in an autosomal recessive pattern. This means a child usually needs to inherit one changed copy from each parent to have HSD17B3-related 46,XY differences in sex development. Parents who each carry one 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. In families asking about the HSD17B3 inheritance pattern, this applies equally to each pregnancy, regardless of previous children.
What does my HSD17B3 result mean for my family?
For families with an HSD17B3-related condition, this usually means both parents are carriers even though they often do not have symptoms themselves. Brothers and sisters may also have the condition or be carriers, so close relatives may want to learn whether the same gene change runs in the family. The chance of health effects is mainly relevant for children with two changed copies, especially those with an XY chromosome pattern.
Genetic information
Genetic testing
How you find out about variants
HSD17B3 genetic testing usually uses a blood or saliva sample, which a lab analyzes to look for variants in the HSD17B3 gene. Results can help confirm whether inherited changes are present and may be compared with parents' samples to see whether both copies of the gene are affected.
When should I consider getting a genetic test?
Genetic testing for HSD17B3 may be considered when a child is born with genitals that look different than expected, when puberty brings unexpected male-type changes, or when there is a family history of this condition. It can help confirm the cause of hormone-related sex development differences and guide care.
A genetic result is only one part of your health story
Genetic results can provide helpful insight, but how much they explain varies by the condition and the type of variant involved. Many factors, including lifestyle, environment, age, and medical history, also influence how the body works over time. In some conditions, especially those shaped by many genes, genetic information provides context rather than certainty and is best understood together with other parts of care. In other situations, a genetic result can offer a clear answer. In areas such as medication response, these results may help put individual experiences into perspective.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. Small inherited differences can change how the body breaks down a drug, moves it through the body, or responds to it at the place where it works, so the same treatment may not feel the same for everyone. These differences are common and can influence how well a medicine works or how sensitive someone is to side effects.
What is Pharmacogenetics?
Pharmacogenetics looks at how genetic differences can affect the way a person responds to medications. It examines gene and drug patterns to help explain why the same treatment may work differently from one person to another. For many medicines, genes influence both how strong a drug’s effects are and how the body processes it. This information can support treatment decisions that are more informed and more personalized. For a closer look at this topic, you can learn more in the LearnHub.
Drugs influenced by the HSD17B3 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding medicine choice or treatment changes. If you have questions about symptoms, treatment, or possible side effects, it is best to talk with your doctor or pharmacist.
History
Doctors first recognized this inherited condition through families in which some children with a 46,XY chromosome pattern were born with sex development that did not follow the usual male pattern. Initially understood only through visible traits, later recognized as tied to a specific gene, it became clearer as hormone testing improved in the late 20th century. In the 1990s, researchers identified the HSD17B3 gene and linked harmful variants to this condition, helping explain cases that had long been difficult to classify. From these first observations, research expanded steadily. That work improved diagnosis, family counseling, and the medical understanding of inherited differences in sex development.