The TMEM138 gene helps cells build and maintain primary cilia, tiny antenna-like structures that guide growth and signaling during early development. If this gene does not work properly, those signals can be disrupted, which may lead to a form of Joubert syndrome. People with pathogenic variants in the TMEM138 gene may have low muscle tone, delayed development, balance or eye movement problems, and sometimes kidney or liver involvement. Effects can vary from person to person.
What is a gene?
A gene is a stretch of DNA that carries instructions your cells use to make molecules or direct activities in the body. Some genes hold the directions for producing proteins, the parts of cells that do the work. Other genes are mainly involved in controlling when certain processes happen, where they take place, and how strongly they operate. Together, genes affect how the body develops and works, and they can also influence how you respond to food, stress, or medications. To go into this topic in more detail, you can find more in the LearnHub.
Overview
TMEM138Gene function
What if the gene works
The TMEM138 gene helps cells build and maintain primary cilia, small structures that act like antennas. These cilia help cells receive signals needed for normal growth and organ development.
Risk
What if the gene does not work
Variants in the TMEM138 gene can cause Joubert syndrome, a condition that can affect balance, eye movements, development, and sometimes the kidneys. Milder and severe variants can change how early features appear and how strongly they affect a person.
Treatment
What does that mean for your treatment
For a pathogenic or loss-of-function variant in the TMEM138 gene, no TMEM138-specific treatment or drug-selection approach is currently established. Treatment is guided by the person’s symptoms and standard care for the affected organs, rather than by the TMEM138 variant itself.
Conditions associated with TMEM138
Gene function
What if the gene works
Your cells use the TMEM138 gene to build and organize primary cilia, tiny hair-like projections that act like antennas. These structures help cells sense signals from their surroundings. TMEM138 mainly works at the base of the cilium, where many parts are assembled and directed into place.
The TMEM138 gene helps cells assemble primary cilia, the tiny antenna-like structures on their surface. This is a core part of how cells build primary cilia for sensing signals and coordinating normal development.
Its protein supports the movement of membrane material and selected proteins toward the growing cilium. This steady delivery helps the cilium form in an organized way and keeps its surface supplied.
TMEM138 works near the base of the cilium in the transition zone (the gate area where materials pass in and out). There, it helps organize traffic so the right components reach the cilium at the right time.
What is a variant?
A genetic variant means there is a small difference in a gene’s DNA sequence. These differences are common and help explain normal variation among people, including appearance, metabolism, and the way the body reacts to environmental factors. Many variants do not have any noticeable effect and are part of usual genetic diversity. Sometimes, though, a variant changes how a gene works more strongly and can contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the TMEM138 gene can change the protein's shape, shorten it, or reduce how much of it the cell makes. Some TMEM138 gene variants have a milder effect, while more disruptive variants can keep the protein from reaching the cilium, a tiny cell projection important for cell signaling, or make it unstable so it breaks down early. In people with Joubert syndrome linked to the TMEM138 gene, more disruptive changes may go along with earlier or more marked features.
How variants are linked to conditions
Pathogenic variants in the TMEM138 gene cause Joubert syndrome, a rare inherited condition that affects brain development, balance, and coordination. TMEM138 gene variants linked to Joubert syndrome may also be associated with eye, kidney, liver, or retinal problems in some people. When a disease-causing TMEM138 variant is found alongside the expected clinical features, it can confirm the diagnosis.
A variant is not necessarily a diagnosis
Variants in genes are a routine part of human biology and are common throughout the general population. Most do not have a direct effect on health and simply reflect natural human variation. 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 influences are involved. In some situations, however, 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 TMEM138-related conditions, risk is mainly set by the genetic changes themselves, usually when both copies of the gene are altered. Family history, having a partner who also carries a TMEM138 change, or parents being related by blood can raise the chance in a child. There is not enough evidence to say lifestyle changes lower this risk.
Inheritance of TMEM138 variants
TMEM138-related conditions are inherited in an autosomal recessive pattern. This means a person usually inherits one changed copy of the TMEM138 gene from each parent, and both parents are typically healthy carriers. When both parents carry a TMEM138 variant, each pregnancy has a 25% chance of the child inheriting both changed copies, a 50% chance of being a carrier, and a 25% chance of inheriting neither changed copy. In practical terms, TMEM138 gene inheritance does not usually involve an affected parent passing the condition directly to every generation.
What does my TMEM138 result mean for my family?
For families with a disease-causing TMEM138 result linked to Joubert syndrome, parents are usually healthy carriers, and brothers or sisters may also be affected or be carriers. Other close relatives, such as siblings of the parents, may also carry the family variant. Because of this, family members may want to talk with their care team about whether genetic testing would be useful for them.
Genetic information
Genetic testing
How you find out about variants
TMEM138 genetic testing uses blood, saliva, or a cheek swab to look for changes in the TMEM138 gene. A lab reads the DNA sequence and compares it with the usual version to find variants. Results may identify a pathogenic variant, a benign variant, or a variant of uncertain significance.
When should I consider getting a genetic test?
Consider genetic testing for the TMEM138 gene if a child has signs of Joubert syndrome, such as low muscle tone, delayed development, unusual eye movements, or a brain scan that fits this condition. Testing can also help when a close family member has Joubert syndrome or a known TMEM138 change.
A genetic result is only one part of your health story
A genetic result can offer useful insight, but what it can tell you varies by the condition and the type of variant involved. Lifestyle, environment, age, and medical history all influence how the body works over time. In some conditions, especially those affected by many genes, genetic information gives context rather than certainty and is most helpful when viewed alongside other parts of care. In other situations, a genetic result may give a clear answer. In areas such as medication response, these results can help put individual experiences into perspective.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how your body handles medicines, so the same treatment may work differently from one person to another. Some people break down a drug more slowly or more quickly, which can change how much medicine stays in the body and for how long. This can influence how well a treatment works or how sensitive someone is to side effects. These differences are common and help explain why medication response is not the same for everyone.
What is Pharmacogenetics?
Pharmacogenetics examines the way genetic variation affects a person’s response to medicines. By looking at links between genes and medications, it helps explain why the same treatment can work differently in different people. For many drugs, genes influence both how much effect a medicine has 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 TMEM138 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding how medicines are chosen or used, so questions about side effects, how well a treatment is working, or medication changes are best discussed with your doctor.