The ABHD5 gene helps cells break down stored fat so your body can use it for energy and keep tissues, including skin, working well. If it does not work properly, fat can build up inside cells and cause a rare inherited condition with dry, scaly skin, liver enlargement, muscle weakness, and other body-wide effects. The protein made by this gene helps your cells manage tiny fat stores inside them, which is especially important in the skin, liver, and muscles.
What is a gene?
A gene is a stretch of DNA that carries instructions your cells use to make molecules or to regulate activities in the body. Some genes provide the directions for producing proteins, which are the working parts of cells. Others mainly help determine when certain processes happen, where they take place, and how active they are. Taken together, genes affect how the body develops and works, and they can shape how you respond to food, stress, or medications. To explore this subject in greater depth, you can find more in the LearnHub.
Overview
ABHD5Gene function
What if the gene works
The ABHD5 gene helps cells break down stored fats for energy. It also supports the skin’s protective barrier by helping make key skin fats.
Risk
What if the gene does not work
When the ABHD5 gene does not work correctly, Chanarin-Dorfman syndrome can result, with scaly skin from birth and fat buildup in the liver, muscles, or other tissues. Milder and more severe variants may affect onset and which features appear.
Treatment
What does that mean for your treatment
No ABHD5-specific treatment or drug selection approach is currently established for people with a pathogenic variant in the ABHD5 gene. Care is based on the person’s symptoms rather than on a gene directed therapy. The ABHD5 gene is being studied in lipid metabolism and fatty liver research, but this has not yet changed routine treatment choices.
Conditions associated with ABHD5
Gene function
What if the gene works
Your cells need a steady way to store fat safely and use it when needed. The ABHD5 gene helps coordinate how cells break down stored fat and make certain protective skin fats. When it works normally, cells can manage fat droplets smoothly and support the skin's outer barrier.
The ABHD5 gene helps cells unlock triglycerides, the main form of stored fat. It switches on partner proteins that release fatty acids so cells can use them for energy and routine upkeep.
Inside many cells, the ABHD5 gene helps keep fat droplets organized and available when fuel is needed. This supports normal fat handling in tissues such as the liver, muscles, and fat tissue.
In skin, the ABHD5 gene also helps make special fats that strengthen the skin's outer barrier. This barrier helps keep moisture in and lowers the chance that everyday irritants can get through.
What is a variant?
A genetic variant is a small difference in the DNA sequence within a gene. These differences are common and help shape normal human diversity, including variation in appearance, metabolism, and how the body responds to environmental influences. Many have no noticeable effect and are simply part of natural genetic variation. In some cases, though, a variant can change how a gene functions more substantially and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
How variants in the ABHD5 gene influence function depends on the change: some make the protein unstable, stop it reaching lipid droplets, or weaken its links with PNPLA2 and PNPLA1. Some missense variants leave partial activity, while truncating or severe splice variants often leave little or no working protein. This difference in residual function can influence how early and how strongly features of Chanarin-Dorfman syndrome appear.
How variants are linked to conditions
Pathogenic variants in both copies of the ABHD5 gene cause Chanarin-Dorfman syndrome, also called neutral lipid storage disease with ichthyosis. This inherited condition is usually present from birth and commonly includes very dry, scaly skin, with some people also developing liver enlargement, muscle weakness, hearing loss, or eye findings. ABHD5 gene variants linked to Chanarin-Dorfman syndrome follow an autosomal recessive pattern, so a person typically inherits one variant from each parent.
A variant is not necessarily a diagnosis
Genetic variants are common across the general population and are a normal feature of human biology. Most do not directly affect health and simply contribute to natural human diversity. For many genes, carrying a variant associated with a condition points to a possible link rather than a certain diagnosis, especially when multiple genes and environmental factors also play a role. In some situations, though, 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 ABHD5, risk is mainly shaped by inheritance: people usually develop the related condition only if they inherit harmful changes in both copies of the gene. A family history of the condition or parents who are blood relatives can raise the chance, while there is not enough evidence to say lifestyle changes lower this inherited risk.
Inheritance of ABHD5 variants
ABHD5-related conditions are inherited in an autosomal recessive pattern. In practical terms, how variants of the ABHD5 gene are inherited usually means a child needs to receive one altered copy from each parent to have the condition. Parents who each carry one ABHD5 gene variant are usually unaffected carriers, and with each pregnancy there is a 25% chance of an affected child, a 50% chance of a carrier child, and a 25% chance of a child without the familial variant. This pattern applies to the well-established ABHD5-related condition known as Chanarin-Dorfman syndrome.
What does my ABHD5 result mean for my family?
For ABHD5, family meaning usually centers on a recessive condition. Parents, brothers, sisters, and adult children may want to know whether they also carry the gene change, especially if there is a family history of dry, scaly skin, liver problems, or muscle weakness linked to this condition. Brothers and sisters can sometimes also be affected, while other relatives may be healthy carriers.
Genetic information
Genetic testing
How you find out about variants
Genetic testing for ABHD5 variants uses a blood or saliva sample to read the DNA code in the ABHD5 gene and compare it with the usual sequence. ABHD5 genetic testing may confirm whether symptoms are linked to this gene and can also show whether a person carries a variant that could be passed on.
When should I consider getting a genetic test?
Consider ABHD5 genetic testing if you or your child has scaly skin from birth along with signs such as an enlarged fatty liver, muscle weakness, or hearing loss, or if this condition runs in the family. Testing can help confirm a rare inherited condition linked to ABHD5 and clarify carrier status for relatives.
A genetic result is only one part of your health story
A genetic result can be informative, but how much it explains varies by the condition and by the kind of variant involved. Over time, many factors, including lifestyle, environment, age, and medical history, also shape how the body works. In some conditions, especially those influenced by many genes, genetic information provides context rather than certainty and is most useful when considered alongside other parts of care. In other situations, a genetic result may offer a clear answer. In areas like medication response, genetic results can also help make sense of individual experiences.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how your body handles certain medicines, so the same treatment may work well for one person but less well for another. These inherited differences can change how quickly a drug is processed or how strongly the body responds to it. This helps explain why people can differ in how much benefit they get from a medication or how sensitive they are to side effects.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences affect response to medications. It focuses on the connection between genes and drugs to better explain why treatments work differently from one person to another. For many medicines, genes influence how strongly a drug works and how the body handles it. This understanding can help support treatment decisions that are more informed and more individualized. More information on this topic is available in the LearnHub.
Drugs influenced by the ABHD5 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in predicting how medicines work, so questions about symptoms, treatment, or side effects are best discussed with your doctor.
History
The ABHD5 gene entered medical genetics through studies of a rare inherited skin and fat storage condition now called Chanarin-Dorfman syndrome. In the late 1990s and early 2000s, researchers linked this condition to changes in the ABHD5 gene, which was first also known as CGI-58. Initially understood only through visible traits, later recognized as tied to a specific gene, the condition became easier to classify and confirm with genetic testing. From these first observations, research expanded steadily, connecting ABHD5 to a broader group of neutral fat storage conditions. Over time, this work helped clinicians move from describing symptoms alone to identifying the inherited cause in affected families.