ABCB11 rs121917938: Understanding This Genetic Variant
The rs121917938 variant is a pathogenic missense mutation located in the ABCB11 gene. It is primarily associated with hereditary liver disorders known as progressive familial intrahepatic cholestasis type 2 (PFIC2) and benign recurrent intrahepatic cholestasis type 2 (BRIC2).
What each genotype means
Typical bile export function
You carry two reference copies of the ABCB11 gene encoding the standard bile salt export pump (BSEP) protein. You do not carry the pathogenic p.Glu297Gly variant associated with progressive familial intrahepatic cholestasis type 2 (PFIC2) or benign recurrent intrahepatic cholestasis (BRIC2). Your baseline risk for these specific genetic bile transport disorders is typical of the general population.
Carried by over 99.9% of individuals across all major global ancestry groups.
PFIC2/BRIC2 carrier
You carry one copy of the pathogenic p.Glu297Gly missense change in the ABCB11 gene alongside one normal allele. Because conditions such as PFIC2 and BRIC2 follow an autosomal recessive pattern of inheritance, single-copy carriers typically do not develop severe progressive childhood cholestasis, though carriers may have an altered susceptibility to transient liver stress such as intrahepatic cholestasis of pregnancy. Reproductive genetic counseling may be considered to assess the carrier status of a reproductive partner.
Extremely rare, observed in fewer than 1 in 10,000 individuals globally in large reference populations like gnomAD.
Elevated risk of intrahepatic cholestasis
You carry two copies of the p.Glu297Gly alteration in the ABCB11 gene, which encodes the bile salt export pump. In published medical genetics literature, carrying two pathogenic ABCB11 alleles in homozygosity or compound heterozygosity is strongly associated with severe autosomal recessive cholestatic disorders, including benign recurrent intrahepatic cholestasis type 2 (BRIC2) and progressive familial intrahepatic cholestasis type 2 (PFIC2). If this finding was not previously identified in a clinical diagnostic setting, consultation with a medical geneticist or hepatologist is recommended for clinical correlation and liver health monitoring.
Extremely rare globally, estimated at far less than 1 in 1,000,000 individuals.
What is the rs121917938 Variant?
The rs121917938 variant is a specific genetic change, or single nucleotide polymorphism (SNP), found within the ABCB11 gene. This gene is located on chromosome 2 and provides the blueprint for a critical protein in the liver. In the context of clinical genetics, this variant is classified as a pathogenic missense mutation. A missense mutation occurs when a single change in the DNA sequence results in the substitution of one amino acid for another in the final protein product. Because the ABCB11 gene is essential for normal liver function, alterations in its sequence can disrupt the production or efficiency of the protein it encodes. Researchers track this specific variant to better understand how inherited changes contribute to the development of cholestatic liver diseases, which are conditions characterized by the impaired flow of bile from the liver.
The Role of the ABCB11 Gene
The ABCB11 gene is responsible for producing the bile salt export pump (BSEP) protein. This protein acts as a molecular pump, moving bile salts out of liver cells (hepatocytes) and into the bile ducts. Bile is a digestive fluid that helps the body break down fats, and the efficient transport of bile salts is vital for maintaining liver health. When the ABCB11 gene contains pathogenic variants, the resulting BSEP protein may be absent, unstable, or unable to function correctly. This failure leads to a buildup of bile salts within the liver cells, which can cause significant cellular stress and damage. The severity of the resulting condition often depends on how much residual function the BSEP protein retains; some mutations cause severe, progressive disease, while others result in milder, intermittent symptoms.
Clinical Associations and Evidence
Scientific research strongly associates pathogenic variants in the ABCB11 gene with a spectrum of liver disorders, specifically PFIC2 and BRIC2. PFIC2 is a severe, progressive form of liver disease that often presents in infancy and can lead to liver failure or the need for a transplant. In contrast, BRIC2 is considered a milder, recurrent form of the condition, where patients experience episodes of jaundice and itching (cholestasis) that may resolve on their own. The evidence linking ABCB11 mutations to these conditions is robust, supported by clinical findings and functional studies showing reduced bile salt transport activity. Because these conditions exist on a spectrum, the clinical presentation can vary significantly between individuals, even those with the same genetic variant, depending on other genetic and environmental factors.
Population Frequency and Prevalence
The rs121917938 variant is considered rare in the general population. Genetic databases like gnomAD track the frequency of such variants across diverse ancestral groups, and pathogenic mutations in ABCB11 are typically found at very low frequencies. Because these conditions are inherited in an autosomal recessive pattern, an individual usually needs to inherit two copies of a pathogenic variant—one from each parent—to manifest the clinical symptoms of PFIC2 or BRIC2. In many cases, individuals who carry only one copy of a pathogenic variant (heterozygotes) do not show symptoms of the disease. Due to the rarity of this specific variant, it is not commonly screened for in general population health panels and is usually identified through targeted clinical testing when a patient presents with unexplained liver symptoms.
Managing Genetic Information
Understanding your genetic status regarding the ABCB11 gene is a matter for clinical consultation. If you or a family member have been identified as a carrier or have received a diagnosis related to this variant, it is essential to work with a medical geneticist or a hepatologist. This information cannot be used to self-diagnose or predict the exact course of a liver condition, as clinical outcomes are influenced by many factors beyond a single SNP. If you are concerned about liver health or family history, discuss these findings with your healthcare provider. They can provide appropriate context, recommend necessary diagnostic tests, and help you understand the implications for your health or family planning. Never make changes to medical treatments or health management strategies based on genetic data without professional clinical guidance.
How common is this variant?
The rs121917938 variant is rare across all major ancestral populations, with a very low allele frequency observed in global genetic databases.
Frequently asked questions
What is the difference between PFIC2 and BRIC2?
PFIC2 is a severe, progressive liver disease that often leads to liver failure in childhood. BRIC2 is a milder, recurrent form characterized by intermittent episodes of cholestasis that do not typically lead to permanent liver damage.
Can I have this variant and not have liver disease?
Yes, because these conditions are autosomal recessive, you generally need two copies of a pathogenic variant to develop the disease. If you have only one copy, you are a carrier and typically do not show symptoms.
How is this variant diagnosed?
Diagnosis is typically confirmed through clinical evaluation by a liver specialist (hepatologist) combined with genetic testing. Genetic testing identifies the specific mutations in the ABCB11 gene.
Is there a cure for ABCB11-related conditions?
Management focuses on treating symptoms and preventing complications. In severe cases of PFIC2, a liver transplant may be necessary, while BRIC2 is often managed with medications to improve bile flow and reduce itching.
Sources & further reading
Educational information only, last refreshed 10/6/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs121917938?
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 — $29