SLCO1B3
Chr 12Digenic recessivesolute carrier organic anion transporter family member 1B3
Also known as: HBLRR, LST-2, LST-3TM13, LST3, OATP-8, OATP1B3, OATP8, SLC21A8
This protein is a liver-specific organic anion transporter that mediates sodium-independent uptake of bile acids, bilirubin, and other organic compounds from blood into hepatocytes. Mutations cause Rotor syndrome, a benign form of conjugated hyperbilirubinemia that typically presents in infancy or childhood with jaundice but normal liver function. The condition follows digenic recessive inheritance, requiring mutations in both SLCO1B1 and SLCO1B3 genes.
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
383 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 | 3 | 0 | 42 | 0 | 45 |
Likely Pathogenic | 3 | 0 | 3 | 0 | 6 |
VUS | 4 | 144 | 44 | 4 | 196 |
Likely Benign | 0 | 11 | 18 | 26 | 55 |
Benign | 0 | 3 | 49 | 4 | 56 |
Conflicting | — | 12 | |||
| Total | 10 | 158 | 156 | 34 | 370 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLCO1B3 · 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
External Resources
Links to major genomics databases and tools