What you carry at this position in your DNA and what research says about it.
Liver and Gut Health: 6/10 evidence, 19 publications.
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Sample genotype (not yours): C/C
Typical Gut Risk but Higher Liver Injury Risk
Processing of certain medications is typical, but there is a higher risk of liver injury from specific antibiotics and tuberculosis therapies. Susceptibility to extensive ulcerative colitis remains at the baseline level.
What this genotype means: Higher risk of liver injury from flucloxacillin; Higher risk of liver injury from anti-tuberculosis drugs; Typical risk of extensive ulcerative colitis.
Sample genotype (not yours): C/T
Mixed Risk for Gut and Liver Health
Slower metabolism of several medications is expected, alongside a higher risk of extensive ulcerative colitis. However, there is a lower risk of liver injury from certain antibiotics and tuberculosis drugs.
What this genotype means: Slower metabolism of tacrolimus and carbamazepine; Increased risk of extensive ulcerative colitis; Lower risk of liver injury from flucloxacillin.
Sample genotype (not yours): T/T
Gene function and biological role
Gene Function: The NR1I2 gene encodes the pregnane X receptor, a nuclear receptor that serves as a master regulator of xenobiotic clearance in the body [1]. It detects foreign chemicals, including a wide range of prescription medications, and coordinates their breakdown and removal [1]. By sensing these compounds, the receptor triggers the expression of key drug-metabolizing enzymes and transport proteins [2]. Beyond drug clearance, this receptor plays a crucial role in maintaining the intestinal barrier and modulating inflammatory responses in the gut [3].
Variant Impact: The rs3814055 variant is located in the promoter region of the NR1I2 gene, where it directly influences how much receptor protein is produced [4]. The C allele is associated with lower baseline promoter activity, resulting in reduced levels of the receptor and decreased induction of downstream enzymes [4] [2]. Conversely, the T allele enhances transcriptional activity, leading to higher receptor levels and altered drug metabolism [4]. This regulatory shift alters how the body processes several common medications and modulates susceptibility to inflammatory conditions in the digestive tract [1].
Key Insight: This variant acts as a genetic volume dial for a master detox receptor, balancing the risk of medication-induced liver damage against the risk of inflammatory bowel conditions.
Location: NR1I2. Chromosome 3 · 3q13.33 · 119.8 Mb
Estimated prevalence by population
Global 42.2%; European 37.7%; African 50.8%; East Asian 60.5%; South Asian 39.6%; Americas 40.0%; Ashkenazi 25.1%; Finnish 40.3%; Middle Eastern 31.5%; Amish 29.6%.
Estimated CC genotype frequency.
Global 45.1%; European 47.4%; African 40.9%; East Asian 34.6%; South Asian 46.7%; Americas 46.5%; Ashkenazi 50.0%; Finnish 46.4%; Middle Eastern 49.3%; Amish 49.6%.
Estimated CT genotype frequency.
Global 12.7%; European 14.9%; African 8.2%; East Asian 4.9%; South Asian 13.8%; Americas 13.5%; Ashkenazi 24.9%; Finnish 13.3%; Middle Eastern 19.3%; Amish 20.8%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Immunity & Inflammation
Chronic Inflammatory Diseases
Ulcerative Colitis. Evidence: 3/10. Source: PMID 17828778. Typical Risk.
Pharmacogenomics
Antimicrobial & Antiviral Response
Flucloxacillin Toxicity. Evidence: 5/10. Source: PMID 20222094. Increased Risk.
Tuberculosis Drug Liver Injury. Evidence: 3/10. Source: PMID 31490979. Increased Risk.
Immunosuppressant & Biologic Response
Tacrolimus Metabolism. Evidence: 6/10. Source: PMID 26882121. Typical.
Showing effects for C/T genotype
Ulcerative Colitis. Evidence: 3/10. Source: PMID 17828778. Increased Risk.
Flucloxacillin Toxicity. Evidence: 5/10. Source: PMID 20222094. Decreased Risk.
Tuberculosis Drug Liver Injury. Evidence: 3/10. Source: PMID 31490979. Decreased Risk.
Tacrolimus Metabolism. Evidence: 6/10. Source: PMID 26882121. Slower.
Showing effects for T/T genotype
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Carrying two copies of the C allele results in lower baseline expression of the pregnane X receptor [1]. This reduced receptor level leads to lower activity of key drug-metabolizing enzymes, particularly CYP3A4 [2]. Consequently, when exposed to certain medications like the antibiotic flucloxacillin, there is a significantly higher risk of drug-induced liver injury [2]. Similarly, clearance of anti-tuberculosis therapies is less efficient, elevating the risk of hepatotoxicity during treatment [3]. On the other hand, this lower receptor activity appears to be protective against certain inflammatory pathways in the gut, keeping the risk of extensive ulcerative colitis at typical levels [4].
Higher risk of liver injury from flucloxacillin; Higher risk of liver injury from anti-tuberculosis drugs; Typical risk of extensive ulcerative colitis.
Sample genotype: CT (Heterozygous)
Carrying one copy of the T allele increases the expression of the pregnane X receptor compared to the typical baseline [1]. This elevated receptor activity enhances the clearance of certain compounds, which lowers the risk of liver injury when taking medications like flucloxacillin [2] or anti-tuberculosis drugs [3]. However, the altered receptor expression also influences the gut's immune response, leading to an increased susceptibility to extensive ulcerative colitis [4].
Slower metabolism of tacrolimus and carbamazepine; Increased risk of extensive ulcerative colitis; Lower risk of liver injury from flucloxacillin.
Sample genotype: TT (Homozygous)
Carrying two copies of the T allele significantly increases the expression of the pregnane X receptor [1]. This elevated receptor activity enhances the clearance of certain compounds, which lowers the risk of liver injury when taking medications like flucloxacillin [2] or anti-tuberculosis drugs [3]. However, the altered receptor expression also influences the gut's immune response, leading to an increased susceptibility to extensive ulcerative colitis [4].
Variants with shared genetic architecture
rs3732356 · NR1I2 Gene · Chr 3 · Cholesterol and Lipids
rs3732359 · NR1I2 Gene · Chr 3 · Cholesterol and Drug Clearance
rs6785049 · NR1I2 Gene · Chr 3 · Drug Metabolism and Gut Health
Role of the PXR gene locus in inflammatory bowel diseases.
A role for the pregnane X receptor in flucloxacillin-induced liver injury.
Influence of a critical single nucleotide polymorphism on nuclear receptor PXR-promoter function.
Content updated August 2026.
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