The DHODH gene gives cells instructions for making an enzyme that helps produce pyrimidines, the building blocks needed for DNA and RNA. In medicine, this gene is important because it supports growth and development, especially before birth. When both copies carry a harmful variant, cells may not make enough of these building blocks, which can disrupt normal development. People with this kind of DHODH change can have Miller syndrome, a rare condition that often affects the face, arms, and legs.
What is a gene?
Genes are pieces of DNA that hold instructions your cells use to make molecules or manage processes throughout the body. Some genes provide the code for proteins, the molecules that do much of the cell’s work. Others are mainly involved in controlling when certain processes happen, where they happen, and how active they are. Taken together, genes affect how your body grows and works, and they can also influence how you react to food, stress, or medications. For a deeper look at this topic, you can read more in the LearnHub.
Overview
DHODHGene function
What if the gene works
The DHODH gene helps cells make pyrimidines, key building blocks for DNA and RNA. This supports normal cell growth, repair, and development, especially in rapidly growing tissues.
Risk
What if the gene does not work
When the DHODH gene does not work properly, it most often causes Miller syndrome, affecting facial and limb development. Variants can be milder or more severe, which may change how early features appear and how marked they are.
Treatment
What does that mean for your treatment
No DHODH-specific treatment or management approach is currently established for people with a pathogenic variant in the DHODH gene. Separately, DHODH is a well-known drug target, and medicines that block this enzyme, such as leflunomide and teriflunomide, are used for other conditions and are also being studied in cancer and infectious disease research.
Conditions associated with DHODH
Gene function
What if the gene works
Your cells need a steady supply of certain building blocks to make genetic material and keep growing. The DHODH gene helps provide part of that supply by supporting a key step in making pyrimidines, which are used to build DNA and RNA. Its protein works in mitochondria, the parts of cells that help manage energy.
The DHODH gene helps cells make pyrimidines, small building blocks used in DNA and RNA. This is part of how the DHODH gene helps cells make DNA and RNA during normal growth and tissue renewal.
By supplying these building blocks, the DHODH gene supports DNA copying and RNA production. That gives cells the material they need to divide, replace worn out cells, and make proteins in a steady way.
Its protein works in mitochondria, the parts of cells that help manage energy. There, it links this building block pathway to the cell's energy system so the reaction can keep moving.
What is a variant?
A genetic variant is a minor change in the DNA sequence within a gene. These changes are common and help explain normal differences among people, such as appearance, metabolism, or the way the body responds to environmental influences. Many variants do not have any noticeable effect and are simply part of natural genetic variation. In some situations, though, a variant changes how a gene works to a greater degree and may contribute to, or directly cause, a genetic condition.
Genetic variants
What if the gene does not work
Variants in the DHODH gene often lower or disrupt the enzyme’s activity, reduce its stability, or change how it fits into the mitochondria, the cell’s energy centers. This helps explain how DHODH gene variants affect protein function and, in some cases, early development. Milder variants may leave some activity intact, while more severe variants can sharply limit pyrimidine production, the supply of DNA and RNA building blocks, and are linked to earlier or more pronounced features of Miller syndrome.
How variants are linked to conditions
Pathogenic variants in the DHODH gene are best known for causing Miller syndrome, a rare inherited condition that affects facial features and the growth of the arms and legs. In this setting, finding disease-causing variants in both copies of the DHODH gene can confirm the diagnosis. This DHODH gene and Miller syndrome link is well established in medical genetics.
A variant is not necessarily a diagnosis
Genetic variants are a usual part of human biology and are common throughout 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 definite diagnosis, especially when several genes and environmental factors also contribute. In some situations, though, a single well-characterized variant in a particular 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 outside factors that increase or reduce health risks related to the DHODH gene. For many living with a DHODH gene change, risk depends mainly on the exact genetic change inherited, so a doctor or genetic counselor can help explain what it may mean for you or your family.
Inheritance of DHODH variants
DHODH-related Miller syndrome follows an autosomal recessive inheritance pattern, which means a person inherits two disease-causing variants in the DHODH gene, one from each parent. In families learning how DHODH variants are inherited, this usually means the parents are healthy carriers who each have one changed copy. When both parents carry a variant in the DHODH gene, each pregnancy has a 25% chance of an affected child, a 50% chance of a child who is a carrier, and a 25% chance of a child with two non-working copies. Sons and daughters are affected equally.
What does my DHODH result mean for my family?
For families with a disease-causing change in the DHODH gene, the condition is usually inherited in a recessive pattern. This often means parents can be healthy carriers, and brothers, sisters, or future children could also be affected or be carriers. Close relatives may also carry the same gene change, so the result can matter beyond one person.
Genetic information
Genetic testing
How you find out about variants
To look for changes in the DHODH gene, genetic testing uses a blood sample, saliva, or a cheek swab to read the gene’s DNA and compare it with the usual sequence. DHODH genetic testing can identify a pathogenic variant, show whether it may run in a family, and help clarify a diagnosis when a related condition is suspected.
When should I consider getting a genetic test?
Genetic testing for the DHODH gene may be considered when a baby or child has a pattern of birth differences affecting the face, ears, and arms or legs that suggests Miller syndrome, or when this condition runs in the family. It can also help clarify carrier status for relatives when a family variant is already known.
A genetic result is only one part of your health story
Genetic results can be informative, but the amount of clarity they provide varies with the condition and the kind of variant involved. Over time, many factors, including lifestyle, environment, age, and medical history, also influence how the body functions. In some conditions, particularly those shaped by many genes, genetic information offers context instead of certainty and makes the most sense when viewed alongside the rest of a person’s care. In other situations, a genetic finding can give a clear answer. For topics like medication response, genetic results may also help make sense of personal experiences.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. This helps explain why the same treatment works well for one person, causes more side effects in another, or seems to have less effect for someone else. Small differences in genes can change how the body absorbs, breaks down, transports, or responds to a drug, and these differences are common.
What is Pharmacogenetics?
Pharmacogenetics examines how differences in genes affect the way people respond to medicines. It studies gene-drug relationships to help explain why the same treatment may not work the same way for everyone. With many drugs, genes can influence both how strongly a medicine works and how the body handles it. This information can support treatment choices that are more informed and tailored to the individual. More detail on this topic is available in the LearnHub.
Drugs influenced by the DHODH gene
When should I seek medical advice?
There isn't yet a broadly confirmed role for this gene in guiding how medicines are prescribed, so questions about treatment, side effects, or new symptoms are best discussed with your doctor.
History
DHODH entered medical genetics more clearly in the early 2010s, when researchers showed that pathogenic variants in the DHODH gene cause Miller syndrome, a rare condition affecting facial and limb development. Before that, the gene was already familiar in drug research because its protein had been studied as a target of medicines such as leflunomide. From these first observations, research expanded steadily. Scientists then connected DHODH to broader questions about cell growth, inherited conditions, and cancer treatment research. Over time, descriptions became more precise as genetic testing linked specific gene changes with recognizable clinical patterns. This history made DHODH important in both rare disease genetics and the long story of medicines designed around human biology.