SLCO1B3
protein-codingsolute carrier organic anion transporter family member 1B3, the group of Solute carrier organic anion transporter family
Gene summary
This gene encodes a liver-specific member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of endogenous and xenobiotic compounds and plays a critical role in bile acid and bilirubin transport. Mutations in this gene are a cause of Rotor type hyperbilirubinemia. Alternative splicing of this gene and the use of alternative promoters results in transcript variants encoding different isoforms that differ in their tissue specificity. [provided by RefSeq, Mar 2017]
- SLC21A8
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~106.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009379
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Gastrointestinal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Inheritance involves SLCO1B1 and SLCO1B3
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLCO1B3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_019844.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 44 | 1 | 50 | ||
| missense | 172 | 17 | 189 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 9 | 3 | 12 | |||
| splice donor/acceptor (+/-2bp) | 1 | 7 | 8 | |||
| Total | 1 | 16 | 180 | 61 | 1 | 259 |
Highest pathogenic variant AF is 0.00013390598
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_062818.1 | 14 | MANE Select | |
| Ensembl | ENSP00000370956.4 | 14 | MANE Select | |
| RefSeq | NP_001336849.1 | 13 | Standard | |
| Ensembl | ENSP00000261196.2 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Methotrexate Pathway, Pharmacokinetics
- Bile secretion - Homo sapiens (human)
- Statin Pathway - Generalized, Pharmacokinetics
- Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics
- Pravastatin Pathway, Pharmacokinetics
Biological Process
- organic anion transport
- bile acid and bile salt transport
- sodium-independent organic anion transport
- transmembrane transport
Molecular Function
- organic anion transmembrane transporter activity
- bile acid transmembrane transporter activity
- sodium-independent organic anion transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- basolateral plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381545
- Coding exons
- 14
- Length
- 279405
- Individuals with no LoFs
- 124516
- Homozygous LoFs
- 10
- Heterozygous LoFs
- 1211
- Defined
- 125737
- p
- 0.00487
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.16 | 412 | 351 | 1.17 | 0.0000164 | 4544 |
| Missense (PolyPhen) | 139 | 118.54 | 1.1726 | 1522 | ||
| Synonymous | -0.606 | 132 | 123 | 1.07 | 0.00000618 | 1315 |
| Loss of Function | -0.774 | 33 | 28.5 | 1.16 | 0.00000120 | 422 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0013 | 0.0013 | notable |
| Latino/Admixed American | 0.0016 | 0.0014 | notable |
| Ashkenazi Jewish | 0.0017 | 0.0017 | notable |
| East Asian | 0.0011 | 0.0010 | notable |
| Finnish | 0.019 | 0.019 | notable |
| European (Non-Finnish) | 0.0057 | 0.0055 | notable |
| South Asian | 0.0011 | 0.0010 | notable |
| Other | 0.0078 | 0.0074 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver. {ECO:0000269|PubMed:22232210}.;
- Disease
- DISEASE: Hyperbilirubinemia, Rotor type (HBLRR) [MIM:237450]: An autosomal recessive form of primary conjugated hyperbilirubinemia. Affected individuals develop mild jaundice not associated with hemolysis shortly after birth or in childhood. They have delayed plasma clearance of the unconjugated anionic dye bromsulphthalein and prominent urinary excretion of coproporphyrin I. Hepatic pigmentation is normal. {ECO:0000269|PubMed:22232210}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- LoFtool
- 0.793
- RVIS EVS
- 0.67
- RVIS percentile EVS
- 84.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0808