SLC25A13 rs74715576: Understanding Citrin Deficiency Carrier Status
The rs74715576 variant is a genetic change located within the SLC25A13 gene, which provides instructions for making a protein called citrin. This variant is recognized as a pathogenic splice donor mutation associated with an increased risk of being a carrier for citrin deficiency, a condition that can lead to metabolic disorders like neonatal intrahepatic cholestasis and adult-onset citrullinemia type II.
What each genotype means
Typical SLC25A13 genotype
This genotype represents the most common genetic sequence at this location. It is not associated with the pathogenic variant linked to citrullinemia type II or neonatal intrahepatic cholestasis.
This is the most common genotype observed across all global populations.
Carrier of pathogenic variant
You carry one copy of the c.852_855del variant, which is a known pathogenic mutation in the SLC25A13 gene. As this condition is inherited in an autosomal recessive manner, carrying a single copy typically does not cause symptoms, but you should discuss the implications for family planning and potential carrier testing for partners with a healthcare provider or genetic counselor.
Carried by approximately 1 in 70 individuals of East Asian ancestry, where this variant is most frequently observed.
Potential risk for citrullinemia
This genotype indicates the presence of two copies of the pathogenic variant. Individuals with this profile may be at risk for developing citrullinemia type II or neonatal intrahepatic cholestasis, conditions that affect the body's ability to process certain amino acids. Please consult with a medical geneticist or metabolic specialist to discuss clinical significance and appropriate follow-up.
This genotype is extremely rare in the general population.
What is the rs74715576 Variant?
The rs74715576 variant is a specific alteration in the DNA sequence of the SLC25A13 gene, located on chromosome 7. In genetic literature, this variant is often identified by its effect on the splicing process, which is how the body edits genetic instructions before they are used to build proteins. Specifically, it is categorized as a pathogenic splice donor variant. This means the change can disrupt the normal production of the citrin protein. Because citrin deficiency is an autosomal recessive condition, an individual typically needs to inherit two copies of a pathogenic variant—one from each parent—to manifest the clinical symptoms of the disease. Being a carrier means an individual has one copy of the variant and one functional copy of the gene, which generally does not result in the disease itself but is important information for family planning and genetic counseling.
The Role of the SLC25A13 Gene
The SLC25A13 gene encodes a protein known as citrin, which functions as a mitochondrial aspartate/glutamate carrier. This protein is essential for the urea cycle, a metabolic process that removes excess nitrogen from the body in the form of urea. Citrin also plays a critical role in the malate-aspartate shuttle, which helps transport energy-related molecules across mitochondrial membranes. When the SLC25A13 gene is mutated, the resulting deficiency in citrin can lead to the accumulation of toxic substances, such as ammonia and citrulline, in the blood. This metabolic disruption is the underlying cause of citrin deficiency, which can manifest as neonatal intrahepatic cholestasis (NICCD) in infants or adult-onset citrullinemia type II (CTLN2). These conditions can cause a range of symptoms, including liver dysfunction and neurological issues, due to the brain's sensitivity to elevated ammonia levels.
Research and Clinical Significance
Research into rs74715576 and other SLC25A13 mutations is primarily focused on East Asian populations, where these variants are more frequently observed. Clinical studies have established that mutations in this gene are the causative factors for citrin deficiency. However, the evidence strength for any single variant's specific clinical impact can be complex, as the severity of the condition can vary even among individuals with similar genetic profiles. Molecular genetic testing is considered the gold standard for diagnosing citrin deficiency, as biochemical markers alone may not always provide a definitive answer. Because the condition is rare and the clinical presentation is highly variable, researchers emphasize that identifying a single pathogenic variant in a carrier does not confirm a diagnosis of the disease. Instead, it highlights the importance of comprehensive genetic screening and consultation with medical geneticists to understand the implications for health and family inheritance.
What You Can Do With This Information
If you have identified that you are a carrier for the rs74715576 variant, it is important to approach this information with perspective. Carrier status for an autosomal recessive condition does not mean you have the disease or will necessarily develop symptoms. The most practical application of this knowledge is for family planning. If you are considering having children, you may wish to discuss your carrier status with a genetic counselor or your healthcare provider. They can help explain the risks of passing the variant to offspring and discuss options for partner testing or prenatal screening. It is essential to remember that this information is for educational purposes and should not be used to diagnose yourself or others. Always consult with a qualified medical professional to interpret genetic results in the context of your personal and family health history.
How common is this variant?
The rs74715576 variant is most prevalent in East Asian populations, with a carrier frequency estimated at approximately 1 in 70 individuals.
Frequently asked questions
What is citrin deficiency?
Citrin deficiency is a rare, inherited metabolic disorder caused by mutations in the SLC25A13 gene. It affects the urea cycle and can lead to liver issues in infants or neurological symptoms in adults.
Does being a carrier mean I have the disease?
No, being a carrier typically means you have one copy of a pathogenic variant and one normal copy of the gene. You generally do not show symptoms of the disease, which is inherited in an autosomal recessive pattern.
Should I be worried if I have this variant?
Identifying this variant is primarily useful for family planning purposes. You should discuss your results with a genetic counselor or physician to understand what it means for your health and your family.
How is citrin deficiency diagnosed?
Diagnosis is typically confirmed through molecular genetic testing of the SLC25A13 gene. Biochemical tests measuring citrulline and ammonia levels in the blood are also used as part of the clinical evaluation.
Sources & further reading
Educational information only, last refreshed 9/27/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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