The SLC25A13 gene helps liver cells move key amino acid building blocks across the mitochondria, which supports energy use, sugar handling, and removal of ammonia. When this gene does not work properly, people can develop citrin deficiency, a genetic condition that may cause jaundice and poor growth in infancy or episodes of confusion and high ammonia later in life. Symptoms vary widely, and some people are not diagnosed until adulthood. Many variants in this gene are harmless, while a few may change how the gene works.
What is a gene?
A gene is a stretch of DNA that carries instructions your cells can use to make molecules or regulate processes in the body. Some genes contain the directions for making proteins, which are the parts of cells that do much of the work. Other genes mainly help control when certain processes happen, where they happen, and how strongly they are carried out. Together, genes affect how the body develops and functions, and they can influence how you respond to food, stress, or medications. To explore this topic in more detail, you can learn more in the LearnHub.
Overview
SLC25A13Gene function
What if the gene works
The SLC25A13 gene makes citrin, a protein that moves certain molecules between parts of cells. This helps the liver use nutrients for energy and clear ammonia through the urea cycle.
Risk
What if the gene does not work
Variants in the SLC25A13 gene can cause citrin deficiency, with infant liver problems or later episodes of confusion from high ammonia. Milder and more severe variants can influence when symptoms begin and how strongly a person is affected.
Treatment
What does that mean for your treatment
Pathogenic variants in the SLC25A13 gene can change treatment by making carbohydrate heavy feeding less suitable, so care often centers on a higher protein, higher fat, lower carbohydrate diet. Intravenous glycerol and large sugar loads are usually avoided because they can worsen metabolic stress, while arginine may help some people. Liver transplantation is an established option when medical and dietary treatment does not provide enough control.
Conditions associated with SLC25A13
Gene function
What if the gene works
Inside your cells, the SLC25A13 gene helps move important molecules in and out of mitochondria, the cell's energy centers. In simple terms, the SLC25A13 gene function supports energy flow and the handling of nitrogen waste. When this system is working normally, cells can make energy and manage routine chemical tasks more smoothly.
The protein made from the SLC25A13 gene sits in the inner membrane of mitochondria, the parts of cells that make energy. It swaps aspartate and glutamate, two amino acids that help cells carry out everyday chemical work.
This carrier is part of the malate-aspartate shuttle, a system that moves energy from the cell fluid into mitochondria. That process helps cells turn nutrients into ATP, the main form of energy cells use.
The aspartate moved by this carrier helps supply the urea cycle, the pathway that clears ammonia from the body. It also supports making glucose and other building blocks that cells need for daily function.
What is a variant?
A genetic variant is a small difference in the DNA sequence of a gene. These differences are common and help shape normal human diversity, including differences in appearance, metabolism, or how the body responds to environmental influences. Many variants do not cause any noticeable effect and simply represent natural genetic variation. Sometimes, 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
Variants in the SLC25A13 gene can make the citrin protein unstable, misshapen, or absent, so it cannot properly move key small molecules across the inner membrane of mitochondria, the cell’s energy centers. Some SLC25A13 gene variants leave a little activity, while more severe variants stop protein production or sharply disrupt its shape. This range of effect helps explain why citrin deficiency may appear earlier or later and with varying features.
How variants are linked to conditions
Pathogenic variants in the SLC25A13 gene cause citrin deficiency, so SLC25A13 gene variants linked to conditions are mainly tied to this inherited group of liver and nutrition-related conditions. In babies, this can appear as neonatal intrahepatic cholestasis caused by citrin deficiency. Later in life, some people develop failure to thrive and dyslipidemia caused by citrin deficiency or adult-onset type II citrullinemia.
A variant is not necessarily a diagnosis
In human biology, genetic variants are common and form a normal part of the differences seen across the general population. Most do not directly affect health and simply reflect natural human diversity. For many genes, having a variant associated with a condition points to a possible link rather than a certain diagnosis, particularly when more than one gene and environmental influences play a role. There are situations, though, where 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 SLC25A13, risk is mainly shaped by whether someone inherits disease-causing changes in both copies of the gene. In people living with citrin deficiency, illness, alcohol, and a high-carbohydrate intake can sometimes trigger or worsen symptoms, especially later in life. There is not enough evidence to say lifestyle changes prevent the condition itself.
Inheritance of SLC25A13 variants
Variants in the SLC25A13 gene are inherited in an autosomal recessive pattern. This means a child usually needs to inherit one altered copy from each parent to have an SLC25A13-related condition. Parents who each carry one variant are often unaffected, and with each pregnancy there is a 25% chance the child will inherit both variants, a 50% chance the child will be a carrier, and a 25% chance the child will inherit neither variant. In practical terms, how SLC25A13 variants are inherited often becomes clear when an unaffected couple has a child with the condition.
What does my SLC25A13 result mean for my family?
For families, an SLC25A13 result usually matters most for brothers, sisters, and future children. Because this gene is linked to a recessive condition, close relatives may also be carriers, and in some families a brother or sister may also have the condition or a milder form. If both parents carry an SLC25A13 change, each pregnancy has a 1 in 4 chance of a child being affected.
Genetic information
Genetic testing
How you find out about variants
To find SLC25A13 variants, genetic testing for SLC25A13 variants usually uses a blood, saliva, or cheek swab sample to read the SLC25A13 gene for changes linked to citrin deficiency. Results may show no variant, one variant, or two variants, which can clarify carrier status or confirm a genetic diagnosis when symptoms fit.
When should I consider getting a genetic test?
Consider SLC25A13 testing if a baby has unexplained jaundice or liver problems, if a child has poor growth and unusual food preferences, or if a teen or adult has episodes of confusion linked to high ammonia. Testing can also help when citrin deficiency runs in the family or a relative is known to carry an SLC25A13 variant.
A genetic result is only one part of your health story
A genetic result can give useful insight, but how much it reveals varies with the condition and the kind of variant involved. Many factors, including lifestyle, environment, age, and medical history, influence how the body functions over time. For some conditions, especially those shaped 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 can offer a clear answer. In areas such as medication response, genetic results can help put individual experiences into perspective.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. Some people break down or move a drug through the body differently, which can change how much of the medicine reaches its target. This kind of variation is common and can influence how well a treatment works or how sensitive someone is to side effects.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences can affect the way a person responds to medication. By looking at connections between genes and drugs, it helps explain why the same treatment may work differently from one person to another. For many medicines, genes influence either how strongly a drug works or how the body processes it. This information can support treatment decisions that are more informed and more individualized. You can read more about this topic in the LearnHub.
Drugs influenced by the SLC25A13 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in predicting how medicines will work or which side effects may happen. If you have concerns about symptoms, supplements, or any medicine you take, talk with your doctor or pharmacist so they can review your overall health and treatment plan.
History
SLC25A13 entered medical genetics through studies of families with citrin deficiency, especially in Japan and other parts of East Asia where inherited patterns had been carefully documented. In the late 1990s, researchers identified the SLC25A13 gene as the cause of adult-onset citrullinemia type II, helping connect a puzzling liver and metabolism condition to a specific inherited change. Soon after, the same gene was linked to a distinct infant condition, neonatal intrahepatic cholestasis caused by citrin deficiency, showing that one gene could be tied to different stages of life. From these first observations, research expanded steadily. Over time, descriptions became more precise, and doctors recognized that the condition was more common than first thought in some populations. These historical steps shaped today’s understanding of SLC25A13-related disease.