ABCB11

Chr 2AR

ATP binding cassette subfamily B member 11

NCBI Gene: 8647ENSG00000073734UniProt: O95342

Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)

Primary Disease Associations & Inheritance

Cholestasis, benign recurrent intrahepatic, 2MIM #605479
AR
Cholestasis, progressive familial intrahepatic 2MIM #601847
AR
597
ClinVar variants
152
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— ABCB11
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
152 Pathogenic / Likely Pathogenic· 285 VUS of 597 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.64LOEUF
pLI 0.000
Z-score 3.95
OE 0.47 (0.35–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.11Z-score
OE missense 0.88 (0.83–0.94)
631 obs / 714.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.47 (0.35–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.83–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 31 / 65.6Missense obs/exp: 631 / 714.3Syn Z: -1.80

ClinVar Variant Classifications

597 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic102
VUS285
Likely Benign140
Benign1
Conflicting19
50
Pathogenic
102
Likely Pathogenic
285
VUS
140
Likely Benign
1
Benign
19
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
5
24
0
50
Likely Pathogenic
43
32
26
1
102
VUS
4
245
23
13
285
Likely Benign
0
6
78
56
140
Benign
0
0
1
0
1
Conflicting
—19
Total6828815270597

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ABCB11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ABCB11-related intrahepatic cholestasis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cholestasis, benign recurrent intrahepatic, 2

MIM #605479

Molecular basis of disorder known

Autosomal recessive

Cholestasis, progressive familial intrahepatic 2

MIM #601847

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ABCB11
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Molecular overview of progressive familial intrahepatic cholestasis.
Amirneni S et al.·World J Gastroenterol
2020Review
Systematic review of progressive familial intrahepatic cholestasis.
Baker A et al.·Clin Res Hepatol Gastroenterol
2019Review
Clinical phenotype of adult-onset liver disease in patients with variants in ABCB4, ABCB11, and ATP8B1.
Nayagam JS et al.·Hepatol Commun
2022Cohort
Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases.
Chen HL et al.·J Biomed Sci
2018Review
Genotype correlates with the natural history of severe bile salt export pump deficiency.
van Wessel DBE et al.·J Hepatol
2020Natural history
Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families.
Strautnieks SS et al.·Gastroenterology
2008
Cholestatic liver disease.
Jüngst C et al.·Dig Dis
2013Review
Clinical phenotype and molecular analysis of a homozygous ABCB11 mutation responsible for progressive infantile cholestasis.
Imagawa K et al.·J Hum Genet
2018Review
[Genetic cholestasis].
Ciocca M et al.·Arch Argent Pediatr
2009
Histological evaluation in biliary diseases.
Saffioti F et al.·Curr Opin Gastroenterol
2023Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Case Report: Sustained biochemical remission following early initiation of odevixibat in an infant with monoallelic ABCB11 mutation and histologically confirmed PFIC2.
Kehler T et al.·Front Pediatr
2025🔓 Open AccessCase report
Loss of Bile Salt Export Pump (Bsep/Abcb11) Ameliorates Toxin-induced Hepatic Fibrosis via Suppression of Hepatocellular Jun Amino-terminal Kinase Signaling and Hepatic Stellate Cell Activation.
Fuchs CD et al.·Cell Mol Gastroenterol Hepatol
2026🔓 Open Access
[Genetic analysis of a child with Progressive familial intrahepatic cholestasis type II due to a homozygous variant of ABCB11 gene].
Zhu W et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025
An ABCB11 variant registry and novel knockin mouse model of PFIC2 based on the clinically relevant ABCB11 E297G variant.
Bell EL et al.·J Lipid Res
2025🔓 Open AccessFunctional
Correction of a Traffic-Defective Missense ABCB11 Variant Responsible for Progressive Familial Intrahepatic Cholestasis Type 2.
Lapalus M et al.·Int J Mol Sci
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
PFIC - Progressive Familial Intrahepatic CholestasisAlagille Syndrome (ALGS)Cholestasis, Intrahepatic

Pediatric Evaluation and Registry for Liver Cholestasis in Canada

NOT YET RECRUITING
NCT07411716Children's Hospital of Eastern OntarioStarted 2026-03
PRS-based Primary Prevention of CVD

Polygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention

ENROLLING BY INVITATION
NCT06820086Phase PHASE4Mikk JÜRISSONStarted 2025-04
Rosuvastatin 20mg

External Resources

Links to major genomics databases and tools