SLCO1B1
protein-codingsolute carrier organic anion transporter family member 1B1, 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 numerous endogenous compounds including bilirubin, 17-beta-glucuronosyl estradiol and leukotriene C4. This protein is also involved in the removal of drug compounds such as statins, bromosulfophthalein and rifampin from the blood into the hepatocytes. Polymorphisms in the gene encoding this protein are associated with impaired transporter function. [provided by RefSeq, Mar 2009]
- SLC21A6
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~108.6 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: Pharmacogenomic
Rationale: For Statin-induced myopathy, the presence of variants may indicate an increased risk of adverse events (eg, with statins), or may additionally be associated with indications for dosing/medication selection (eg, with rifampin)
Comments: For Hyperbilirubinemia, Rotor type, digenic, inheritance involves SLCO1B1 and SLCO1B3
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLCO1B1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006446.5. 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 | 4 | 13 | 4 | 21 | ||
| missense | 90 | 7 | 2 | 99 | ||
| nonsense | 1 | 2 | 1 | 4 | ||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 4 | 5 | |||
| splice donor/acceptor (+/-2bp) | 4 | 6 | 10 | |||
| Total | 1 | 7 | 106 | 20 | 6 | 140 |
Highest pathogenic variant AF is 0.0016211185
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006437.3 | 14 | MANE Select | |
| Ensembl | ENSP00000256958.2 | 14 | MANE Select | |
| Ensembl | ENSP00000540237.1 | 14 | Standard | |
| Ensembl | ENSP00000540237.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Methotrexate Pathway, Pharmacokinetics
- Rosiglitazone Pharmacokinetic Pathway
- Bile secretion - Homo sapiens (human)
- Statin Pathway - Generalized, Pharmacokinetics
- Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics
Biological Process
- organic anion transport
- bile acid and bile salt transport
- sodium-independent organic anion transport
- transmembrane transport
- thyroid hormone transport
Molecular Function
- bile acid transmembrane transporter activity
- sodium-independent organic anion transmembrane transporter activity
- thyroid hormone transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- membrane
- basolateral plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000256958
- Coding exons
- 14
- Length
- 108045
- Individuals with no LoFs
- 124942
- Homozygous LoFs
- 8
- Heterozygous LoFs
- 783
- Defined
- 125733
- p
- 0.00315
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.897 | 404 | 356 | 1.13 | 0.0000169 | 4482 |
| Missense (PolyPhen) | 141 | 124.16 | 1.1357 | 1516 | ||
| Synonymous | 0.319 | 119 | 124 | 0.963 | 0.00000586 | 1313 |
| Loss of Function | -0.0422 | 32 | 31.7 | 1.01 | 0.00000150 | 428 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.032 | 0.032 | notable |
| Latino/Admixed American | 0.0024 | 0.0024 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0051 | 0.0045 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00032 | 0.00032 | rare |
| South Asian | 0.0026 | 0.0026 | notable |
| Other | 0.0012 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver. {ECO:0000269|PubMed:10358072, ECO:0000269|PubMed:10601278, ECO:0000269|PubMed:12196548, ECO:0000269|PubMed:22232210}.;
Recessive Scores
- pRec
- 0.198
Intolerance Scores
- LoFtool
- 0.994
- RVIS EVS
- 1.03
- RVIS percentile EVS
- 91.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0264
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |