The SIX1 gene helps guide early development of the ears, kidneys, and parts of the face and neck. If it does not work properly, a person may be born with hearing loss, differences in ear shape, small pits or lumps on the side of the neck, or kidney changes. The protein made by this gene helps your cells switch other genes on at the right time before birth. Pathogenic variants in the SIX1 gene are linked to some cases of branchio-otic syndrome and branchio-oto-renal syndrome.
What is a gene?
Genes are stretches of DNA that carry instructions cells use to make molecules or regulate activity in the body. Some provide the information needed to produce proteins, which are the parts of cells that do much of the work. Others mainly direct when certain processes take place, where they occur, and how active they are. Taken together, genes affect how the body develops and works, 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
SIX1Gene function
What if the gene works
The SIX1 gene helps control other genes during early development. It supports the formation of the ears, kidneys, muscles, and parts of the head and neck.
Risk
What if the gene does not work
Variants in the SIX1 gene are linked to conditions that can affect hearing, outer ear shape, neck pits or cysts, and sometimes kidney development. Effects range from mild to more severe, depending on the variant.
Treatment
What does that mean for your treatment
No treatment or management approach is currently established specifically for pathogenic or loss of function variants in the SIX1 gene. The SIX1 gene is being studied as a biomarker and possible drug target in several cancers.
Conditions associated with SIX1
Gene function
What if the gene works
Before birth, the SIX1 gene helps guide how key body structures take shape. It is especially active during early development, when cells need clear instructions about when to grow, move, and mature. Knowing what the SIX1 gene does helps explain how tissues form in an organized way.
The SIX1 gene helps switch other genes on or off in early developing cells. This gives cells the right instructions at the right time.
SIX1 helps young cells keep dividing until enough cells are available to build a tissue. It also helps them mature at the right stage.
During development, SIX1 supports the formation of parts of the ears, face, neck, kidneys, and muscles. It helps these tissues grow in a coordinated pattern.
SIX1 works with partner proteins in the cell nucleus, the control center that manages gene activity. Together, they fine tune developmental signals so tissues form smoothly.
What is a variant?
A genetic variant is a slight change in a gene’s DNA sequence. Variants are common and are one reason people differ naturally in traits such as appearance, metabolism, and the body’s response to environmental influences. Many variants do not lead to any noticeable effect and only reflect normal genetic variation. Sometimes, however, a variant changes how a gene functions more markedly and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the SIX1 gene can alter the protein’s shape or activity, weakening how it binds DNA or works with partner proteins such as EYA1. Some missense variants partly reduce this control, while more disruptive variants can sharply lower the amount of working protein or keep it from reaching the cell nucleus. This SIX1 gene variant effect can range from mild to near-complete loss of activity. That spectrum may help explain why hearing loss and branchio-oto-renal features vary from person to person.
How variants are linked to conditions
Pathogenic variants in the SIX1 gene can cause branchio-oto-renal spectrum conditions, including branchio-otic syndrome and branchio-oto-renal syndrome, which often involve hearing loss, ear differences, neck pits or cysts, and sometimes kidney changes. Some variants in the SIX1 gene are also linked to inherited hearing loss without kidney findings. For families reading about SIX1 gene hearing loss and kidney problems, these conditions usually run in families because a parent carrying the variant can pass it on.
A variant is not necessarily a diagnosis
Genetic variants are a usual feature of human biology and are common across the general population. Most do not directly affect health and instead represent natural 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 are involved. In some situations, though, one well-characterized variant in a specific 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 factors that increase or reduce health risks related to the SIX1 gene. For many living with a SIX1 change, the main factor is the gene variant itself, while the type and severity of symptoms can still vary within the same family.
Inheritance of SIX1 variants
The inheritance of the SIX1 gene variants is usually autosomal dominant. That means a parent carrying a disease-causing SIX1 variant can pass it to a child with a 50% chance in each pregnancy. Sons and daughters are affected at similar rates, and either parent can pass the variant on. In families with SIX1-related conditions, the variant often appears across generations rather than only among siblings.
What does my SIX1 result mean for my family?
A harmful change in the SIX1 gene is usually passed down in families in a dominant pattern, so close relatives like parents, brothers, sisters, and children may also carry the same change. This can matter because SIX1 is linked to hearing loss and, in some families, differences in the ears, neck area, or kidneys. Some cases happen for the first time in one family member, so a parent does not always have the same gene change.
Genetic information
Genetic testing
How you find out about variants
SIX1 genetic testing for hearing loss looks for variants in the SIX1 gene, usually from a blood or saliva sample. A lab reads the gene's DNA code to see whether a variant may help explain hearing loss or features of branchio-oto-renal syndrome, with results interpreted alongside your medical and family history.
When should I consider getting a genetic test?
Genetic testing for the SIX1 gene may be worth considering if you or your child has hearing loss along with small ear pits, neck lumps or cysts, or kidney problems, especially when these run in the family. It can also help clarify a suspected inherited condition that affects the ears, neck, and kidneys.
A genetic result is only one part of your health story
A genetic finding can provide meaningful insight, but how much it explains varies based on the condition and the specific type of variant. Many other factors, including age, environment, lifestyle, and medical history, also shape how the body works over time. In some conditions, especially those influenced by many genes, genetic information gives context rather than certainty and is best understood alongside other parts of care. In other situations, a genetic result can give a clear answer. In areas such as 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 responds to medicines. Some people break down a drug more slowly or more quickly than others, so the same treatment can feel stronger, weaker, or last for a different amount of time. These inherited differences are common and can influence both how well a medicine works and how likely side effects are.
What is Pharmacogenetics?
Pharmacogenetics examines how differences in genes can shape the way a person responds to medications. By looking at links between genes and drugs, it helps explain why the same treatment may work differently from one person to another. For many medicines, genes can affect both how strongly a drug works and how the body processes it. This information can support more informed, individualized treatment decisions. More detail on this topic is available in the LearnHub.
Drugs influenced by the SIX1 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in predicting how someone will respond to medicines, so concerns about side effects, new symptoms, or medication changes are best discussed with your doctor.
History
Inheritance patterns were noticed long before the gene was identified. The SIX1 gene entered modern genetics through work on a fruit fly gene called sine oculis, which helped researchers understand how organs develop. In the 1990s, scientists identified human SIX family genes, including SIX1, and linked them to early development in the ear, muscles, and other tissues. Building on this early work, researchers found that variants in the SIX1 gene can be involved in branchio otic syndrome and branchio oto renal syndrome, helping explain why certain features run in families. Over time, descriptions became more precise as genetic testing improved and clinicians could connect specific SIX1 variants with a person’s symptoms. These historical steps shaped today’s understanding of SIX1 in human development and inherited conditions.