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SLCO1B1
solute carrier organic anion transporter family member 1B1
The SLCO1B1 gene encodes the OATP1B1 protein, an important transporter in the liver that facilitates the removal of various compounds, including certain medications, from the body. The SLCO1B1 gene provides instructions for creating the OATP1B1 protein, which plays a critical role in the liver by transporting substances from the bloodstream into liver cells for processing and elimination.
SLCO1B1 is located on the short (p) arm of chromosome 12, at band 12p12.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The SLCO1B1 gene is responsible for producing organic anion transporting polypeptide 1B1 (OATP1B1), a protein predominantly found in liver cells. This protein acts as a key transporter, moving various compounds from the blood into the liver. Once inside the liver, these substances can be metabolised and subsequently cleared from the body.
Its function extends to critical physiological processes, including the removal of bilirubin, which is a yellowish byproduct of red blood cell breakdown. OATP1B1 also facilitates the clearance of certain hormones, toxins, and a range of pharmaceutical drugs, notably statins used for high cholesterol, some heart disease medications, specific antibiotics, and certain cancer treatments.
What the gene does
The OATP1B1 protein, encoded by the SLCO1B1 gene, is strategically located in liver cells, where its primary role is to mediate the uptake of organic anions from the circulating blood into the hepatocytes. This transport mechanism is crucial for detoxification pathways and drug metabolism. An example of its function is the transport of bilirubin, a metabolic waste product, into the liver. In the liver, bilirubin is conjugated and then secreted into bile for excretion.
Beyond endogenous substances like bilirubin and certain hormones, OATP1B1 is a major determinant of the pharmacokinetics of numerous clinically important drugs. These include HMG-CoA reductase inhibitors (statins), which are widely prescribed for cholesterol management, as well as some antiviral agents, antibiotics, and anticancer drugs. The efficiency of this protein's transport function can significantly influence drug concentrations in the blood, thereby affecting both the efficacy and potential toxicity of these medications. Variations in the SLCO1B1 gene can therefore impact how an individual processes and responds to certain drug therapies.
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Chromosome location
The SLCO1B1 gene is situated on chromosome 12, specifically at position 12p12.1. This precise genomic address helps geneticists and researchers pinpoint its location within the human genome. The gene contains instructions for assembling a protein comprising 691 amino acids.
Protein structure
The OATP1B1 protein consists of 691 amino acids. While a comprehensive domain architecture has not been fully elucidated for the entire protein, a specific domain known as the Kazal-like domain has been identified. This domain spans amino acid positions 453 to 508, suggesting it may play a role in the protein's overall structure or function, although its precise contribution in OATP1B1 is not fully understood.
Key variants
Genetic variants, or polymorphisms, within the SLCO1B1 gene can influence the activity and efficiency of the OATP1B1 protein. These changes can affect how effectively the protein transports substances into the liver. Some common variations have been identified that are associated with altered drug metabolism, particularly for statins. These variants typically result in a reduced ability of the OATP1B1 protein to transport specific drugs or endogenous compounds, potentially leading to higher drug levels in the bloodstream. The clinical impact of these variants is often assessed in the context of pharmacogenomics, evaluating how an individual's genetic makeup affects their response to medications.
Sample of pathogenic variants
2 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1738C>T | p.Arg580Ter | Pathogenic | ★★☆☆ | Rotor syndrome |
c.757C>T | p.Arg253Ter | Pathogenic | ★★☆☆ | Rotor syndrome |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variations within the SLCO1B1 gene are associated with certain health conditions and drug responses. For example, specific mutations in SLCO1B1, often in combination with mutations in a related gene, SLCO1B3, are implicated in Rotor syndrome. This condition is characterised by elevated levels of bilirubin in the blood, which can lead to jaundice. Additionally, common genetic variations in SLCO1B1 are known to influence how the body processes certain drugs, including statins, impacting their effectiveness and potential side effects.
No disease links recorded for this gene in our reference set.
UK clinical status
The SLCO1B1 gene is considered relevant in the UK clinical context, particularly within pharmacogenomics. While it may not be routinely included on every broad genetic screening panel, its role in drug metabolism, especially for statins, means it is of interest in personalised medicine approaches. The gene's actionable status indicates that genetic information related to SLCO1B1 can inform clinical decisions, such as drug dosing or choice, to optimise treatment outcomes and minimise adverse reactions for individuals.
Diet & lifestyle considerations
Research suggests that certain lifestyle choices can influence liver health, which is pertinent given the SLCO1B1 gene's role in liver transport. Maintaining a balanced diet and regular physical activity generally supports liver function. While there is no direct evidence that specific lifestyle interventions can alter SLCO1B1 gene expression or protein activity, supporting overall hepatic health can indirectly benefit the liver's capacity to metabolise and clear substances from the body. Individuals should discuss any lifestyle changes with a healthcare provider.
Supplement considerations
Currently, there is no conclusive scientific evidence to suggest that specific supplements can alter SLCO1B1 gene activity or the function of the OATP1B1 protein in a clinically beneficial way. Any claims that supplements can enhance drug metabolism or prevent conditions related to SLCO1B1 function should be viewed with scepticism. Individuals considering any supplements, particularly if on medication, should always consult their healthcare provider to avoid potential interactions or adverse effects.
Frequently asked questions
What is the primary role of the SLCO1B1 gene?
The SLCO1B1 gene provides instructions for making the OATP1B1 protein, which acts as a transporter in the liver. Its main function is to move various compounds, including bilirubin, hormones, toxins, and many medications, from the bloodstream into liver cells for clearance from the body.
How does SLCO1B1 relate to medications?
The OATP1B1 protein, produced from the SLCO1B1 gene, transports several types of drugs into the liver for metabolism. This is particularly relevant for statins, certain heart disease medications, antibiotics, and some cancer treatments. Variations in the gene can affect how an individual processes these drugs, influencing their effectiveness and potential side effects.
What is Rotor syndrome and its connection to SLCO1B1?
Rotor syndrome is a condition characterised by elevated levels of bilirubin in the blood, leading to jaundice. It is associated with mutations in the SLCO1B1 gene, typically in combination with mutations in a related gene called SLCO1B3.
Can diet or lifestyle affect SLCO1B1 function?
While there's no direct evidence that specific dietary or lifestyle interventions directly impact SLCO1B1 gene activity, maintaining general liver health through a balanced diet and regular exercise can support the liver's overall metabolic functions, including those involving OATP1B1.
What does 'pharmacogenomics' mean in relation to SLCO1B1?
Pharmacogenomics refers to how an individual's genes affect their response to drugs. For SLCO1B1, this means that genetic variations can influence how effectively the body processes certain medications, potentially guiding healthcare providers in selecting appropriate drug dosages or alternative treatments to optimise patient care.
References
- van de Steeg E, Stránecký V, Hartmannová H. Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. The Journal of clinical investigation. 2012. PMID: 22232210
- Niemi M, Pasanen MK, Neuvonen PJ. Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacological reviews. 2011. PMID: 21245207
- Voora D, Shah SH, Spasojevic I. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. Journal of the American College of Cardiology. 2009. PMID: 19833260
- SEARCH Collaborative Group, Link E, Parish S. SLCO1B1 variants and statin-induced myopathy--a genomewide study. The New England journal of medicine. 2008. PMID: 18650507
- Cui Y, König J, Leier I. Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. The Journal of biological chemistry. 2001. PMID: 11134001