SLCO1B3 (OATP1B3) Gene: Function, Expression, and Clinical Significance
A comprehensive overview of the SLCO1B3 gene, encoding the organic anion transporting polypeptide 1B3 (OATP1B3), including its genomic context, tissue expression, role in drug disposition, associated diseases, and notable genetic variants.
Gene Information Card
| Symbol | SLCO1B3 |
|---|---|
| Full Name | Solute Carrier Organic Anion Transporter Family Member 1B3 |
| Gene Type | Protein coding |
| Chromosomal Location | 12p12.2 |
| NCBI Gene ID | 28234 ncbi.nlm.nih.gov/gene/28234 |
| Ensembl ID | ENSG00000111700 |
| UniProt ID | Q9NPD5 |
| OMIM ID | 605495 |
| HGNC ID | 10960 |
| Aliases | OATP1B3, OATP8, SLC21A8, LST-2 |
Description
The SLCO1B3 gene encodes the organic anion transporting polypeptide 1B3 (OATP1B3), a transmembrane protein primarily expressed on the basolateral (sinusoidal) membrane of human hepatocytes. This transporter mediates the sodium-independent uptake of a wide range of endogenous and exogenous compounds from the portal blood into the liver. Substrates include bile salts, bilirubin, steroid hormones, thyroid hormones, and numerous clinically important drugs such as statins, antibiotics, and anticancer agents. SLCO1B3 plays a critical role in hepatic drug clearance and disposition, influencing drug efficacy and toxicity. Its expression is also detected in various cancer tissues, where it may affect tumor progression and response to chemotherapy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rotor Syndrome | SLCO1B1 and SLCO1B3 are co-deleted or mutated, leading to a complete deficiency of both OATP1B1 and OATP1B3 transporters in the liver. This impairs hepatic uptake of bilirubin and other organic anions, causing mild conjugated hyperbilirubinemia. | ClinVar, OMIM |
| Hepatocellular Carcinoma (HCC) | Expression of SLCO1B3 is often downregulated in HCC tissues compared to normal liver. This altered expression may affect the uptake of endogenous substrates and chemotherapeutic drugs, potentially contributing to tumor progression and multidrug resistance. | NCBI Gene, PubMed |
| Drug-Induced Liver Injury (DILI) | Genetic variants in SLCO1B3 can alter the hepatic uptake of drugs, potentially increasing the risk of drug-induced liver injury. For example, reduced function variants may lead to higher systemic drug concentrations and altered hepatic exposure. | ClinVar, PubMed |
| Hyperbilirubinemia | Reduced function of OATP1B3, particularly in combination with OATP1B1 variants, can impair bilirubin transport, contributing to elevated bilirubin levels and jaundice in certain conditions. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | High expression is observed in hepatocytes. |
| Kidney | Low | Low expression is detected in renal tubular cells. |
| Small Intestine | Low | Low expression is found in enterocytes. |
| Pancreas | Low | Low expression is present in pancreatic acinar cells. |
| Colon | Low | Low expression is detected in colonic epithelium. |
| Lung | Not detected | Expression is generally not detected in normal lung tissue. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | High | Hepatocellular carcinoma cell line with high endogenous expression. |
| Caco-2 | Low | Colorectal adenocarcinoma cell line with low expression. |
| HEK293 | Not detected | Human embryonic kidney cells typically do not express SLCO1B3. |
| A549 | Not detected | Lung carcinoma cell line with no detectable expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.174C>G (p.Ser58Arg) | Missense | Rare | This variant has been associated with reduced transport activity for certain substrates, potentially affecting drug disposition. |
| c.334T>C (p.Phe112Leu) | Missense | Rare | A non-synonymous variant that may alter the protein's function, though its clinical significance is still under investigation. |
| c.699G>A (p.Met233Ile) | Missense | Rare | This variant has been studied for its impact on the transport of methotrexate and other anticancer drugs, with some studies suggesting altered activity. |
| c.1559A>C (p.His520Pro) | Missense | Rare | A variant that has been shown to affect the cell surface expression and transport function of OATP1B3 in vitro. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SLCO1B3, often in conjunction with SLCO1B1, are a primary cause of Rotor syndrome. These mutations lead to a complete absence or non-functional OATP1B3 protein, impairing hepatic bilirubin and organic anion uptake.
Gain of Function (GOF)
No clear gain-of-function mutations have been definitively characterized for SLCO1B3. Some variants may show altered substrate specificity or increased transport of certain compounds, but these are not typically classified as classic gain-of-function.
Dominant Negative (DN)
There is no strong evidence for dominant-negative effects of SLCO1B3 mutations. The transporter functions as a monomer, and the main disease mechanism is associated with biallelic loss of function.
View complete mutation data：
Gene Ontology (GO)
| • Organic anion transmembrane transporter activity | • Bile acid:sodium symporter activity |
| • Transmembrane transport | • Integral component of plasma membrane |
| • Response to xenobiotic stimulus | • Cellular response to organic cyclic compound |
Pathways
• Hepatic drug clearance
• Bile acid and bilirubin transport
• Organic anion transport
• Statins pharmacokinetics pathway
• Methotrexate transport
Protein Summary
The OATP1B3 protein is a 702-amino acid, 12-transmembrane domain glycoprotein belonging to the SLC21A/SLCO superfamily of organic anion transporters. It is localized to the basolateral membrane of hepatocytes, where it functions as an electrogenic, sodium-independent transporter. The protein mediates the cellular uptake of a broad spectrum of amphipathic organic compounds, including bile salts, bilirubin glucuronides, steroid conjugates, thyroid hormones, and numerous drugs. OATP1B3 shares high sequence homology with OATP1B1 (SLCO1B1), but they have distinct, yet overlapping, substrate specificities. The protein's expression is regulated by various nuclear receptors, including HNF1α and HNF4α, and can be downregulated in certain disease states like hepatocellular carcinoma.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLCO1B3 Knockout HEK293 Cell Line | EDJ-KQ51220 | Human | 28234 | Details Get a Quote |
| SLCO1B3 Knockout HeLa Cell Line | EDJ-KQ56071 | Human | 28234 | Details Get a Quote |
| SLCO1B3 Knockout A-549 Cell Line | EDJ-KQ64555 | Human | 28234 | Details Get a Quote |
| SLCO1B3 Knockout HCT 116 Cell Line | EDJ-KQ73013 | Human | 28234 | Details Get a Quote |
