ABCB11

protein-coding

ATP binding cassette subfamily B member 11, the group of ATP binding cassette subfamily B

Gene summary

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]

Previous symbols:

BSEP
PFIC2

MANE transcript

NM_003742.4

Inheritance

ClinVar variants

P:452U:659B:589

Top phenotype

Cholestasis, progressive familial intrahepatic 2

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr2:168,915,498-169,031,324

External References & Databases

Ensembl (ENSG00000073734)

Transcript & Mutation Effects

hg38 • Region Span ~115.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

progressive familial intrahepatic cholestasis type 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011156

Submitter: Labcorp Genetics (formerly Invitae)

progressive familial intrahepatic cholestasis type 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011156

Submitter: G2P

progressive familial intrahepatic cholestasis type 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011156

Submitter: Natera

benign recurrent intrahepatic cholestasis type 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011559

Submitter: Labcorp Genetics (formerly Invitae)

progressive familial intrahepatic cholestasisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015762

Submitter: PanelApp Australia

progressive familial intrahepatic cholestasis type 2SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011156

Submitter: Orphanet

Clinical Genomic Database (CGD)

Cholestasis, progressive familial intrahepatic 2AR

Manifestation: Gastrointestinal; Oncologic

Intervention: Gastrointestinal; Oncologic

Rationale: In severe forms, specific nutritional care may be beneficial (eg, including specific vitamin E supplementation); Individuals are at high risk for hepatocellular carcinoma early in life, and surveillance and early treatment may be beneficial; Recurrence after liver transplant may benefit from immunosuppresive treatment; Liver transplant may be indicated

Comments: The condition may involve multiple interacting variants

Refs: 9806540; 10579978; 15300568; 16039748; 16871584; 20301474; 19797282; 21055686; 21766090; 21219577; 22675952

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABCB11 variants in ClinVar

17 Conditions Cataloged

not providedTotal: 1319

Familial intrahepatic cholestasisTotal: 670

Progressive familial intrahepatic cholestasis type 2Total: 540

ABCB11-related disorderTotal: 290

Benign recurrent intrahepatic cholestasis type 2Total: 179

not specifiedTotal: 144

Inborn genetic diseasesTotal: 108

Progressive familial intrahepatic cholestasisTotal: 32

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003742.4. 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		3 clinvar	25 clinvar	521 clinvar	7 clinvar	556
missense	11 clinvar	111 clinvar	628 clinvar	58 clinvar	3 clinvar	811
nonsense	60 clinvar	44 clinvar	2 clinvar			106
start loss	2 clinvar	2 clinvar				4
frameshift	81 clinvar	56 clinvar	1 clinvar			138
splice donor/acceptor (+/-2bp)	27 clinvar	55 clinvar	3 clinvar			85
Total	181	271	659	579	10	1700

Highest pathogenic variant AF is 0.0002653431

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003742.4	RefSeq	NP_003733.2	27	MANE Select
ENST00000650372.1	Ensembl	ENSP00000497931.1	27	MANE Select
ENST00000439188.1	Ensembl	ENSP00000416058.1	2	Standard
ENST00000647920.1	Ensembl	ENSP00000497947.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
abcb11b	Danio rerio	Structure: hepatocyte Quality: swollen abnormal

Gene / Model

Organism

Observed Phenotype

abcb11b

Danio rerio

Structure: hepatocyte

Quality: swollen

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Bile secretion - Homo sapiens (human)
ABC transporters - Homo sapiens (human)
Cholesterol metabolism - Homo sapiens (human)
Statin Pathway - Generalized, Pharmacokinetics
Pravastatin Pathway, Pharmacokinetics

Biological Process

bile acid biosynthetic process
bile acid and bile salt transport
canalicular bile acid transport
sodium ion transmembrane transport
ATP hydrolysis coupled cation transmembrane transport

Molecular Function

transporter activity
ATP binding
sodium-exporting ATPase activity, phosphorylative mechanism
canalicular bile acid transmembrane transporter activity
bile acid-exporting ATPase activity

Cellular Component

plasma membrane
integral component of plasma membrane
membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263817
Coding exons: 27
Length: 108385
Individuals with no LoFs: 124592
Homozygous LoFs: 0
Heterozygous LoFs: 76
Defined: 124668
p: 0.000305

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.11	631	714	0.883	0.0000370	8645
Missense (PolyPhen)		227	286.79	0.79152		3364
Synonymous	-1.80	284	248	1.15	0.0000129	2557
Loss of Function	3.95	31	65.6	0.473	0.00000340	779

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00046	0.00045	rare
Latino/Admixed American	0.00058	0.00058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00057	0.00056	rare
Other	0.00066	0.00066	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.;
Disease: DISEASE: Cholestasis, progressive familial intrahepatic, 2 (PFIC2) [MIM:601847]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. {ECO:0000269|PubMed:10579978, ECO:0000269|PubMed:11815775, ECO:0000269|PubMed:24969679, ECO:0000269|PubMed:9806540}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cholestasis, benign recurrent intrahepatic, 2 (BRIC2) [MIM:605479]: A disorder characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically. {ECO:0000269|PubMed:15300568, ECO:0000269|PubMed:16039748}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.393

Intolerance Scores

RVIS EVS: -1.14
RVIS percentile EVS: 6.39

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.176

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium