UGT1A1 rs4148324: What Your Genotype Means
The rs4148324 variant, commonly known as UGT1A1*6, is a genetic change in the UGT1A1 gene that reduces the body's ability to process bilirubin and certain medications. It is primarily studied for its role in Gilbert syndrome and its impact on how patients metabolize the chemotherapy drug irinotecan.
What each genotype means
Normal enzyme function
You carry two copies of the standard G allele, which corresponds to the normal-function UGT1A1*1 allele at this locus. Research indicates normal baseline glucuronidation activity via this pathway, which is associated with typical clearance of bilirubin and medications metabolized by UGT1A1, such as irinotecan. Because other genetic variants or clinical factors can influence drug processing, discuss medication choices and standard dosing with your healthcare provider or pharmacist.
Carried by approximately 55% to 75% of individuals of East Asian ancestry and nearly 100% of individuals of European and African ancestries.
Intermediate enzyme function
You carry one copy of the decreased-function A allele, often designated in pharmacogenomics literature as UGT1A1*6 (p.Gly71Arg). This genotype is statistically associated with moderately reduced UGT1A1 enzyme activity and intermediate metabolism, which in East Asian cohorts has been linked to higher circulating levels of irinotecan's active metabolite and elevated risk of neutropenia. If you are prescribed irinotecan or other UGT1A1-processed drugs, review pharmacogenetic guidance and dosing considerations with your physician or pharmacist.
Carried by approximately 20% to 30% of East Asian populations, but found in fewer than 1% of individuals of European or African descent.
Poor enzyme function
You carry two copies of the decreased-function A allele (homozygous UGT1A1*6/*6), which substantially reduces UGT1A1 enzyme activity to roughly thirty percent of typical levels. In East Asian populations where this variant is prevalent, this genotype is strongly associated with an increased susceptibility to severe irinotecan toxicity, including severe neutropenia, as well as unconjugated hyperbilirubinemia. It is important to share these results with your doctor or pharmacist so they can evaluate dosage adjustments or tailored monitoring if you receive therapies cleared by this pathway.
Carried by approximately 2% to 6% of East Asian individuals, while remaining extremely rare or virtually absent in European and African populations.
Understanding the Variant and Its Location
The variant rs4148324 is a single nucleotide polymorphism (SNP) located within the UGT1A1 gene on chromosome 2. In this specific position, a guanine (G) is replaced by an adenine (A). This change results in a missense mutation where the amino acid glycine is replaced by arginine at position 71 of the UGT1A1 protein, often referred to as p.Gly71Arg. Because this change occurs in the coding region of the gene, it can alter the structure and function of the resulting enzyme. This variant is widely recognized in scientific literature as the UGT1A1*6 allele. It is distinct from other common UGT1A1 variants, such as the TA-repeat polymorphism known as UGT1A1*28, which affects the gene's promoter region rather than the protein-coding sequence itself.
The Role of the UGT1A1 Gene
The UGT1A1 gene provides instructions for making an enzyme called UDP-glucuronosyltransferase 1A1. This enzyme is essential for a process called glucuronidation, which makes substances more water-soluble so they can be easily excreted from the body. One of its primary jobs is to process bilirubin, a yellow pigment produced when red blood cells break down. When UGT1A1 activity is reduced, bilirubin can build up in the blood, potentially leading to jaundice or conditions like Gilbert syndrome. Beyond bilirubin, this enzyme is also responsible for detoxifying various drugs, including the chemotherapy agent irinotecan. By attaching a glucuronic acid molecule to the active metabolite of irinotecan (SN-38), the enzyme helps clear the drug from the system. If the enzyme is less efficient, the drug may remain in the body longer, increasing the risk of side effects.
Research and Clinical Associations
Research has established a strong link between the UGT1A1*6 variant and reduced enzyme function. Individuals who carry this variant, particularly those who are homozygous (having two copies), are at a higher risk for hyperbilirubinemia and Gilbert syndrome. In the context of pharmacogenomics, this variant is a significant predictor of toxicity for patients treated with irinotecan. Reduced glucuronidation capacity means that patients may experience higher levels of the drug's active metabolite, leading to an increased risk of severe adverse events such as neutropenia and diarrhea. While the evidence for these associations is robust in East Asian populations, it is considered limited in other groups where the variant is rare. Clinical guidelines often suggest that clinicians consider these genetic factors when determining appropriate dosing for patients undergoing irinotecan-based chemotherapy to minimize toxicity.
Population Frequency
The frequency of the rs4148324 (UGT1A1*6) variant varies significantly by ancestry. It is relatively common in East Asian populations, including Japanese, Korean, and Chinese individuals, where allele frequencies typically range from 15% to 30%. Conversely, this variant is extremely rare in European and African populations, where other variants like UGT1A1*28 are more prevalent. Because of this distribution, the clinical relevance of testing for rs4148324 is most pronounced in patients of East Asian descent.
What You Can Do With This Information
Genetic information regarding UGT1A1 is a tool for personalized medicine, not a diagnostic test for general health. If you are aware that you carry the rs4148324 variant, it is important to understand that this does not mean you have a disease, but rather that your body may process certain substances differently. If you are prescribed medications metabolized by UGT1A1, such as irinotecan, you should discuss your genetic status with your oncologist or pharmacist. They can use this information to adjust dosages or monitor you more closely for potential side effects. Never make changes to your medication regimen based on genetic test results without consulting a healthcare professional. Always ensure that any genetic testing is interpreted in the context of your overall health, medical history, and other clinical factors.
How common is this variant?
The rs4148324 variant is common in East Asian populations, with allele frequencies between 15% and 30%, but it is rare in European and African populations.
Frequently asked questions
Is rs4148324 the same as Gilbert syndrome?
The rs4148324 variant is one of several genetic factors associated with Gilbert syndrome. While it can contribute to the condition, having the variant does not guarantee a diagnosis, as other genetic and environmental factors also play a role.
Does this variant affect all medications?
No, this variant specifically affects the metabolism of drugs processed by the UGT1A1 enzyme, such as irinotecan. It does not impact the metabolism of most other common medications.
Should I get tested for UGT1A1 variants?
Genetic testing for UGT1A1 is typically recommended by clinicians before starting specific treatments like irinotecan. You should discuss the necessity of this test with your doctor based on your specific treatment plan.
Can I change my UGT1A1 genotype?
No, your genotype is determined at birth and cannot be changed. However, knowing your genotype allows your healthcare team to make informed decisions about your medical care.
Sources & further reading
Educational information only, last refreshed 10/18/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs4148324?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in UGT1A1
Missense variant corresponding to the functional UGT1A1*27 allele associated with reduced glucuronidation and elevated irinotecan toxicity risk.
Variant allele in UGT1A1 promoter region associated with altered glucuronidation and risk of irinotecan-induced toxicity.
Missense alteration associated with reduced glucuronidation capacity and increased susceptibility to irinotecan toxicity and hyperbilirubinemia.
This variant in the UGT1A gene cluster is associated with serum total bilirubin levels and susceptibility to Gilbert syndrome.
This variant is a key marker for defining UGT1A1 star alleles (*1, *28, *36, *37) which influence the metabolism of drugs like irinotecan and the risk of hyperbilirubinemia.
This variant is associated with hyperbilirubinaemia (Gilbert's syndrome) and is used to guide irinotecan dosage.