SLC51A

Chr 3AR

solute carrier family 51 member A

ENSG00000163959 UniProt: Q86UW1 OMIM: 612084

The SLC51A protein is an essential component of the Ost-alpha/Ost-beta transporter complex that exports bile acids from intestinal cells into portal blood circulation. Mutations cause progressive familial intrahepatic cholestasis type 6, a liver disease with autosomal recessive inheritance. The gene shows moderate constraint to loss-of-function variants (LOEUF 0.631), reflecting its important role in bile acid transport and enterohepatic circulation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Essential component of the OST-alpha/OST-beta complex, a heterotetramer that acts as the intestinal basolateral transporter responsible for bile acid export from enterocytes into portal blood (PubMed:16317684, PubMed:41606314, PubMed:41606328). The OST-alpha/OST-beta complex efficiently transports the major species of bile acids (taurocholate) (PubMed:16317684, PubMed:41606314, PubMed:41606328). Taurine conjugates are transported more efficiently across the basolateral membrane than glycine-conjugated bile acids (By similarity). In the complex, SLC51A/OST-alpha adopts a G protein-coupled receptor fold and constitutes a bile acid recognition site (PubMed:41606314, PubMed:41606328). Can also transport steroids such as estrone 3-sulfate and dehydroepiandrosterone 3-sulfate, therefore playing a role in the enterohepatic circulation of sterols (PubMed:16317684). Able to transport eicosanoids such as prostaglandin E2 (By similarity)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Cholestasis, progressive familial intrahepatic, 6MIM #619484

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.63

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.070

Z-score 2.65

OE 0.30 (0.16–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.22Z-score

OE missense 0.95 (0.85–1.08)

184 obs / 192.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.16–0.63)

0≤0.351.4

Missense OE?0.95 (0.85–1.08)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 5 / 16.7Missense obs/exp: 184 / 192.8Syn Z: 1.32

Background carrier burden — how many people carry a rare variant somewhere in SLC51A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

510 rare PASS variants

Rare truncating (LoF)

1 in 930

92 rare PASS variants

Rare synonymous (reference)

1 in 170

239 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC51A. 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 150	1 in 1,000
South Asian	~43k	1 in 100	1 in 1,800
Remaining (unassigned)	~30k	1 in 79	1 in 750
European (Finnish)	~27k	1 in 330	≈ 1 in 13,000
Admixed American	~22k	1 in 86	1 in 920
African / African American	~21k	1 in 91	1 in 1,400
East Asian	~20k	1 in 140	1 in 1,700
Ashkenazi Jewish	~13k	1 in 350	≈ 1 in 5,900
Middle Eastern	~2,884	1 in 75	≈ 1 in 670

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): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓