SLCO1B1

Chr 12Digenic recessive

solute carrier organic anion transporter family member 1B1

Also known as: HBLRR, LST-1, OATP-C, OATP1B1, OATP2, OATPC, SLC21A6

NCBI Gene: 10599 ENSG00000134538 UniProt: Q9Y6L6 OMIM: 604843

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hyperbilirubinemia, Rotor type, digenicMIM #237450

Digenic recessive

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Hyperbilirubinemia, Rotor type, digenic; no ClinGen or GenCC tier

Active trials

168

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.35

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — SLCO1B1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.35LOEUF

pLI 0.000

Z-score -0.04

OE 1.01 (0.76–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.90Z-score

OE missense 1.13 (1.04–1.23)

404 obs / 356.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.01 (0.76–1.35)

0≤0.351.4

Missense OE?1.13 (1.04–1.23)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 32 / 31.7Missense obs/exp: 404 / 356.3Syn Z: 0.32

Background carrier burden — how many people carry a rare variant somewhere in SLCO1B1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

976 rare PASS variants

Rare truncating (LoF)

1 in 270

191 rare PASS variants

Rare synonymous (reference)

1 in 270

300 rare PASS variants

Rare missense and truncating variants are carried at similar rates in SLCO1B1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 88	1 in 860
South Asian	~43k	1 in 58	1 in 190
Remaining (unassigned)	~30k	1 in 43	1 in 370
European (Finnish)	~27k	1 in 250	1 in 1,500
Admixed American	~22k	1 in 59	1 in 290
African / African American	~21k	1 in 57	1 in 230
East Asian	~20k	1 in 44	1 in 510
Ashkenazi Jewish	~13k	1 in 350	≈ 1 in 12,000
Middle Eastern	~2,882	1 in 40	1 in 310

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 14 coding exons well covered in gnomAD exomes; exon 13 poorly covered; exons 2, 5, 6, 7, 14, 15 marginal. Genomes: 13 of 14 (exon 13 below).? see exons ↓