SLCO1B1
Chr 12Digenic recessivesolute carrier organic anion transporter family member 1B1
Also known as: HBLRR, LST-1, OATP-C, OATP1B1, OATP2, OATPC, SLC21A6
The protein functions as a liver-specific organic anion transporter that mediates sodium-independent uptake of endogenous compounds including bilirubin, bile acids, and hormones, as well as drugs like statins. Mutations cause Rotor type hyperbilirubinemia through digenic recessive inheritance, requiring variants in both this gene and another gene for disease manifestation. This gene is not constrained against loss-of-function variants, consistent with its recessive inheritance pattern.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
266 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 42 | 0 | 42 |
Likely Pathogenic | 4 | 0 | 4 | 0 | 8 |
VUS | 9 | 84 | 30 | 4 | 127 |
Likely Benign | 0 | 6 | 11 | 10 | 27 |
Benign | 0 | 5 | 40 | 7 | 52 |
Conflicting | — | 4 | |||
| Total | 13 | 95 | 127 | 21 | 260 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLCO1B1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Polygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention
ENROLLING BY INVITATIONPharmacogenomics-Supported Psychotropic Prescribing Trial
RECRUITINGLiver Adiposity Effects on Pediatric Statin
RECRUITINGPersonalised Hyperlipidaemia Therapies Guided by Pharmacogenomics
NOT YET RECRUITINGPharmacogenomics Applied to Chronic Pain Treatment in Primary Care
ACTIVE NOT RECRUITINGProspective Observational Association Between SLCO1B1 Gene Polymorphism and the Anti-factor Xa Activity of Edoxaban in Patients With Moderate to Severe Renal Insufficiency
RECRUITINGPharmacogenetic Supported Prescribing in Kids
RECRUITINGExternal Resources
Links to major genomics databases and tools