What you carry at this position in your DNA and what research says about it.
Bilirubin and Drug Clearance: 5/10 evidence, 6 publications.
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Sample genotype (not yours): T/T
Typical Bilirubin Levels and Standard Drug Clearance
Normal UGT1A1 enzyme activity characterizes this genetic profile. Bilirubin levels are typically in the normal range, and there is a standard clearance rate for drugs like irinotecan.
What this genotype means: Standard bilirubin clearance; Typical risk of chemotherapy side effects.
Sample genotype (not yours): G/G
Elevated Bilirubin Levels and High Drug Sensitivity
Double copies of the G allele significantly reduce UGT1A1 enzyme activity. Slower clearance increases the likelihood of elevated bilirubin levels and raises the risk of severe toxicity from specific chemotherapy drugs.
What this genotype means: Higher baseline bilirubin levels; High risk of severe chemotherapy-induced neutropenia.
Sample genotype (not yours): T/G
Moderately Elevated Bilirubin and Increased Drug Sensitivity
A single copy of the G allele reduces UGT1A1 enzyme production. Slower processing can lead to slightly higher bilirubin levels and an increased risk of side effects from certain medications.
What this genotype means: Moderately higher bilirubin levels; Increased risk of irinotecan-induced neutropenia.
Gene function and biological role
Gene Function: The UGT1A10 gene belongs to the UDP-glucuronosyltransferase family, which plays a critical role in the body's detoxification processes. This family of enzymes is responsible for glucuronidation, a process that renders toxins, hormones, and drugs water-soluble for excretion [1]. Specifically, these enzymes are essential for clearing bilirubin, a byproduct of red blood cell breakdown [1]. They also metabolize various therapeutic drugs, including certain chemotherapies [2]. Variations in this gene family can significantly alter enzyme activity, leading to differences in drug tolerance and bilirubin levels [1] [2].
Variant Impact: The variant rs4124874, also known as UGT1A1*60, is a single nucleotide polymorphism located in the promoter region of the UGT1A gene cluster [3]. This genetic change from a thymine (T) to a guanine (G) reduces the transcriptional activity of the UGT1A1 promoter by approximately 60% [3]. As a result, individuals carrying the G allele produce fewer functional UGT1A1 enzymes [2]. This reduction in enzyme levels impairs the liver's ability to process bilirubin and clear specific medications [3] [2].
Key Insight: This variant reduces the promoter activity of the UGT1A1 gene by about 60 percent, directly impacting how the liver processes both natural waste products and chemotherapy drugs.
Location: UGT1A1. Chromosome 2 · 2q37.1 · 233.8 Mb
Estimated prevalence by population
Global 22.6%; European 31.6%; African 3.2%; East Asian 45.3%; South Asian 16.9%; Americas 26.5%; Ashkenazi 21.4%; Finnish 25.8%; Middle Eastern 25.0%; Amish 26.8%.
Estimated TT genotype frequency.
Global 43.7%; European 49.2%; African 29.5%; East Asian 44.0%; South Asian 48.4%; Americas 50.0%; Ashkenazi 49.7%; Finnish 50.0%; Middle Eastern 50.0%; Amish 49.9%.
Estimated TG genotype frequency.
Global 33.7%; European 19.2%; African 67.3%; East Asian 10.7%; South Asian 34.6%; Americas 23.6%; Ashkenazi 28.9%; Finnish 24.2%; Middle Eastern 25.0%; Amish 23.3%.
Estimated GG genotype frequency.
Showing effects for T/T genotype
Organ Systems
Liver Function & Disease
Bilirubin Levels. Evidence: 3/10. Source: PMID 24865931. Typical.
Pharmacogenomics
Chemotherapy Response
Irinotecan Toxicity. Evidence: 5/10. Source: PMID 15007088. Typical Risk.
Showing effects for G/G genotype
Bilirubin Levels. Evidence: 3/10. Source: PMID 24865931. Significantly Higher.
Irinotecan Toxicity. Evidence: 5/10. Source: PMID 15007088. High Risk.
Showing effects for T/G genotype
Bilirubin Levels. Evidence: 3/10. Source: PMID 24865931. Increased.
Irinotecan Toxicity. Evidence: 5/10. Source: PMID 15007088. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Standard levels of the UGT1A1 enzyme are produced by those with the T/T genotype [1]. This enzyme is crucial for conjugating bilirubin, allowing it to be safely excreted from the body [1]. Consequently, there is a lower risk of developing unconjugated hyperbilirubinemia or neonatal jaundice [1]. Additionally, when undergoing chemotherapy treatments such as irinotecan or FOLFIRI, this genotype is associated with a standard rate of drug clearance [2]. This normal metabolism helps minimize the risk of severe side effects like neutropenia or bone marrow suppression [2].
Standard bilirubin clearance; Typical risk of chemotherapy side effects.
Sample genotype: GG (Homozygous)
Two copies of the UGT1A1*60 promoter variant significantly reduce the expression of the UGT1A1 enzyme [1]. This reduction impairs the liver's ability to conjugate bilirubin, often leading to elevated unconjugated bilirubin levels in the blood, a hallmark of Gilbert's syndrome [1]. Furthermore, this genotype is strongly linked to an increased risk of severe toxicities when treated with irinotecan or FOLFIRI chemotherapy regimens [2]. Slower drug clearance can lead to severe bone marrow suppression and neutropenia [2].
Higher baseline bilirubin levels; High risk of severe chemotherapy-induced neutropenia.
Sample genotype: TG (Heterozygous)
Carrying one copy of the G allele (also known as UGT1A1*60) moderately decreases the transcriptional activity of the UGT1A1 promoter [1]. With reduced enzyme levels, the liver processes bilirubin less efficiently, which can elevate serum bilirubin levels [1]. In medical scenarios, this reduced capacity becomes particularly important during chemotherapy with irinotecan [2]. The slower clearance of the drug's active metabolite increases the risk of developing severe neutropenia, a condition marked by low white blood cell counts [2]. Discussing these genetic tendencies with a healthcare provider can help tailor treatment plans if these medications are ever prescribed.
Moderately higher bilirubin levels; Increased risk of irinotecan-induced neutropenia.
Variants with shared genetic architecture
rs6742078 · UGT1A1 Gene · Chr 2 · Gallstone Risk
rs887829 · UGT1A1 Gene · Chr 2 · Bilirubin and Heart Health
rs10929302 · UGT1A1 Gene · Chr 2 · Drug and Bilirubin Clearance
Content updated August 2026.
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