ABCB11

Chr 2AR

ATP binding cassette subfamily B member 11

Also known as: ABC16, BRIC2, BSEP, PFIC-2, PFIC2, PGY4, SPGP

NCBI Gene: 8647 ENSG00000073734 UniProt: O95342 OMIM: 603201

This gene encodes the bile salt export pump, which transports bile salts across the canalicular membrane of hepatocytes in an ATP-dependent manner and is essential for hepatic bile acid homeostasis. Mutations cause progressive familial intrahepatic cholestasis type 2 and benign recurrent intrahepatic cholestasis type 2, both presenting with severe cholestatic liver disease that can manifest from early infancy. The inheritance pattern is autosomal recessive.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is the major canalicular bile salt export pump in man. Mutations in this gene cause a form of progressive familial intrahepatic cholestases which are a group of inherited disorders with severe cholestatic liver disease from early infancy. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.642 OMIM phenotypes

Clinical Summary— ABCB11

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

208 unique Pathogenic / Likely Pathogenic· 513 VUS of 1022 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.95

OE 0.47 (0.35–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.11Z-score

OE missense 0.88 (0.83–0.94)

631 obs / 714.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.35–0.64)

0≤0.351.4

Missense OE?0.88 (0.83–0.94)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 31 / 65.6Missense obs/exp: 631 / 714.3Syn Z: -1.80

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveABCB11-related intrahepatic cholestasisLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.83top 10%

GOF

0.81top 10%

LOF

0.1993th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

1022 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic116

Likely Pathogenic92

VUS513

Likely Benign153

Benign31

Conflicting114

116

Pathogenic

Likely Pathogenic

513

VUS

153

Likely Benign

Benign

114

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	109	6	1	0	116
Likely Pathogenic	54	29	9	0	92
VUS	5	443	45	20	513
Likely Benign	0	10	79	64	153
Benign	0	1	20	10	31
Conflicting	—				114
Total	168	489	154	94	1,019

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap ABCB11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →