The SIX3 gene helps guide early development of the brain, eyes, and middle of the face before birth. If it does not work properly, the front part of the brain may not divide in the usual way, which can lead to holoprosencephaly, a condition that affects brain and facial development. Some people with variants in the SIX3 gene have severe findings, while others have milder changes.
What is a gene?
A gene is a stretch of DNA that holds instructions your cells use to make molecules or regulate activities in the body. Some genes provide the directions for producing proteins, which are the parts of cells that do much of the work. Others mainly help manage when certain processes happen, where they take place, and how active they are. Taken together, genes affect how the body grows and works, and they can influence how you react to food, stress, or medicines. For a more detailed look at this topic, you can find additional information in the LearnHub.
Overview
SIX3Gene function
What if the gene works
The SIX3 gene helps guide early development of the front part of the brain and the eyes. It helps control when other genes turn on during these steps.
Risk
What if the gene does not work
Variants in the SIX3 gene can disrupt early brain and face development, most often causing holoprosencephaly. Effects range from severe brain malformations to milder midline facial changes, and more disruptive variants often cause earlier, broader features.
Treatment
What does that mean for your treatment
No SIX3-specific treatment or management approach is currently established. A pathogenic variant in the SIX3 gene does not currently point to a unique drug choice, so care is guided by a person’s symptoms and clinical findings rather than the gene variant itself.
Conditions associated with SIX3
Gene function
What if the gene works
Early in pregnancy, the developing brain and eyes rely on the SIX3 gene to follow a clear body plan. It helps direct other genes, so cells in the front of the embryo know what to become. Understanding how the SIX3 gene works helps you see how early brain and eye development stays organized.
The SIX3 gene gives cells instructions for a protein that turns many other genes on or off during early development. This helps young cells follow the right plan as major body structures begin to form.
The SIX3 gene helps set up the front part of the developing brain, called the forebrain. It guides nearby cells so early brain regions form in the right place and with the right identity.
During early development, the SIX3 gene supports the first steps of eye formation. It helps tissues that will become the eyes and nearby structures grow in coordination with the developing brain.
Inside early embryonic tissues, the SIX3 gene helps balance growth signals that shape the head. This steady signaling is a key part of how the SIX3 gene helps the forebrain and eyes form.
What is a variant?
A genetic variant is a minor change in a gene’s DNA sequence. These changes are common and are part of normal human diversity, including differences in appearance, metabolism, and the way the body responds to environmental influences. Many variants do not have any noticeable effect and are simply part of natural genetic variation. Sometimes, though, a variant changes how a gene works more significantly and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the SIX3 gene can change the shape, stability, or DNA binding ability of its protein, so it cannot control other developmental genes as effectively during very early embryo growth. In SIX3 gene variants linked to holoprosencephaly, some changes leave part of the protein working, while more disruptive variants can sharply reduce or eliminate its activity. This range in functional impact may influence how early differences in brain and facial development appear and how marked they are.
How variants are linked to conditions
Pathogenic variants in the SIX3 gene are a well-established cause of holoprosencephaly type 2, a condition in which the front of the brain and face develop differently before birth. Signs linked to SIX3 gene variants can range from mild facial differences or learning and hormone issues to major brain changes, so the effect can vary widely even within families. In rare cases, related findings such as eye or pituitary abnormalities are also reported.
A variant is not necessarily a diagnosis
Variants in genes are a usual part of human biology and are widely found in the general population. Most do not directly affect health and instead reflect normal human diversity. For many genes, having a variant associated with a condition suggests a possible link rather than a definite diagnosis, especially when several genes and environmental factors play a role. In some situations, though, one well-characterized variant in a particular gene is enough to confirm a diagnosis.
Are there things that can increase or change my risk?
For SIX3, risk is mainly shaped by whether a disease-causing gene change is present, and the effects can vary even within the same family. Changes in other genes and pregnancy-related factors such as poorly controlled diabetes or alcohol exposure may influence how strongly this condition shows up. There is not enough evidence to say that lifestyle changes can reliably lower risk once a SIX3 variant is present.
Inheritance of SIX3 variants
For families asking how SIX3 gene variants are inherited, the main recognized pattern is autosomal dominant. That means a person with a disease-causing variant in one copy of the SIX3 gene can pass it to a son or daughter, and each child has a 1 in 2, or 50%, chance of inheriting that variant. Some people with a SIX3 gene variant are the first in their family to have it because the variant arose new in them rather than being inherited from either parent.
What does my SIX3 result mean for my family?
A disease-causing change in the SIX3 gene is usually passed down in a dominant way, so close relatives such as parents, brothers, sisters, and children may also carry the same change and may want to discuss family testing. In some families, the same gene change can affect people very differently, from no obvious symptoms to significant brain and facial differences. Some SIX3 changes happen new in a child, so a parent does not always carry the result.
Genetic information
Genetic testing
How you find out about variants
SIX3 genetic testing uses a blood or saliva sample to look for variants in the SIX3 gene. To understand how SIX3 genetic testing works, a lab reads the gene's DNA, often through a multigene panel or exome test, and classifies any finding as pathogenic, benign, or uncertain.
When should I consider getting a genetic test?
Consider SIX3 testing if a baby or pregnancy has shown major differences in early brain development, especially holoprosencephaly, or if this condition runs in your family. Testing can help clarify the cause and whether close relatives may also carry the gene change.
A genetic result is only one part of your health story
A genetic result can be informative, but how much it reveals 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. For some conditions, especially those shaped by many genes, genetic information offers context rather than certainty and is best considered alongside other parts of care. In other situations, a genetic result may give a clear answer. In areas such as medication response, genetic results can help put individual 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 breaks down a drug, moves it through the bloodstream, or responds to it at its target. This is common and helps explain why the same treatment works well for one person, has less effect in another, or causes more side effects in someone else. Along with age, liver and kidney function, and other medicines, genetic differences are one of the reasons medication response can vary from person to person.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences affect the way people respond to medicines. By studying the relationship between genes and drugs, it helps explain 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 processes it. This information can support treatment decisions that are more informed and more individualized. More detailed information on this topic is available in the LearnHub.
Drugs influenced by the SIX3 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in how medicines work, so questions about symptoms, treatment, or medication side effects are best discussed with your doctor.
History
SIX3 came into medical genetics through research on how the early brain and eyes form in embryos, building on work from animal studies in the 1990s. Initially understood only through visible traits, later recognized as tied to a specific gene, SIX3 became an important clue in explaining some cases of holoprosencephaly, a condition in which the front of the brain does not separate in the usual way before birth. From these first observations, research expanded steadily. Scientists then identified pathogenic variants in the SIX3 gene in affected families, which helped confirm its place in developmental genetics. Over time, this work shaped genetic testing panels used to investigate certain differences in early brain development.