ABCB11

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

Basic information

Region (hg38): 2:168915497-169031324

Previous symbols: [ "BSEP", "PFIC2" ]

Links

ENSG00000073734 ∙ NCBI:8647 ∙ OMIM:603201 ∙ HGNC:42 ∙ Uniprot:O95342 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• progressive familial intrahepatic cholestasis type 2 (Definitive), mode of inheritance: AR
• progressive familial intrahepatic cholestasis type 2 (Supportive), mode of inheritance: AR
• progressive familial intrahepatic cholestasis type 2 (Strong), mode of inheritance: AR
• benign recurrent intrahepatic cholestasis type 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cholestasis, progressive familial intrahepatic 2	AR	Gastrointestinal; Oncologic	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	Gastrointestinal; Oncologic	9806540; 10579978; 15300568; 16039748; 16871584; 20301474; 19797282; 21055686; 21766090; 21219577; 22675952
The condition may involve multiple interacting variants

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCB11 gene.

• not provided (1096 variants)
• Progressive familial intrahepatic cholestasis type 2 (219 variants)
• Benign recurrent intrahepatic cholestasis type 2 (121 variants)
• not specified (83 variants)
• Inborn genetic diseases (22 variants)
• Progressive familial intrahepatic cholestasis (19 variants)
• ABCB11-related condition (19 variants)
• Progressive familial intrahepatic cholestasis type 2;Benign recurrent intrahepatic cholestasis type 2 (15 variants)
• Cholestasis, intrahepatic, of pregnancy, 3 (9 variants)
• Benign recurrent intrahepatic cholestasis type 2;Progressive familial intrahepatic cholestasis type 2 (8 variants)
• Familial intrahepatic cholestasis type 2 (5 variants)
• Intrahepatic cholestasis;Pruritus;Abnormal liver function tests during pregnancy (1 variants)
• Progressive familial intrahepatic cholestasis type 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCB11 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	2	8	370	10	391
missense	20	40	186	25	4	275
nonsense	37	12				49
start loss	1					1
frameshift	47	16	1			64
inframe indel			2			2
splice donor/acceptor (+/-2bp)	15	27	1			43
splice region		3	18	64	4	89
non coding			15	101	109	225
Total	121	97	213	496	123

Highest pathogenic variant AF is 0.000125

Variants in ABCB11

This is a list of pathogenic ClinVar variants found in the ABCB11 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-168922952-C-G		Progressive familial intrahepatic cholestasis type 2	Uncertain significance (Jan 13, 2018)
2-168922982-C-G		Progressive familial intrahepatic cholestasis type 2	Uncertain significance (Jan 12, 2018)
2-168923089-G-T		Progressive familial intrahepatic cholestasis type 2	Uncertain significance (Jan 13, 2018)
2-168923113-G-A		Progressive familial intrahepatic cholestasis type 2	Uncertain significance (Jan 13, 2018)
2-168923182-C-T		Progressive familial intrahepatic cholestasis type 2	Likely benign (Jan 13, 2018)
2-168923202-T-C		Progressive familial intrahepatic cholestasis type 2	Benign (Jan 13, 2018)
2-168923216-T-C		Progressive familial intrahepatic cholestasis type 2	Uncertain significance (Jan 13, 2018)
2-168923254-C-T		Progressive familial intrahepatic cholestasis type 2	Benign (Jan 13, 2018)
2-168923306-C-T		Progressive familial intrahepatic cholestasis type 2	Uncertain significance (Jan 12, 2018)
2-168923341-A-C		Progressive familial intrahepatic cholestasis type 2	Uncertain significance (Jan 13, 2018)
2-168923370-A-T		Progressive familial intrahepatic cholestasis type 2	Uncertain significance (Jan 12, 2018)
2-168923385-A-G		Progressive familial intrahepatic cholestasis type 2	Likely benign (Jan 12, 2018)
2-168923386-T-C		Progressive familial intrahepatic cholestasis type 2	Benign (Jun 29, 2018)
2-168923429-C-G		Progressive familial intrahepatic cholestasis	Uncertain significance (Jun 14, 2016)
2-168923596-T-C		Progressive familial intrahepatic cholestasis type 2	Uncertain significance (Jan 13, 2018)
2-168923616-A-T		not specified	Likely benign (Feb 10, 2016)
2-168923626-C-G			Uncertain significance (Mar 09, 2022)
2-168923626-C-T		Progressive familial intrahepatic cholestasis type 2 • ABCB11-related disorder	Conflicting classifications of pathogenicity (Jan 09, 2024)
2-168923631-G-C			Likely benign (Aug 14, 2023)
2-168923634-G-A			Likely benign (Apr 28, 2023)
2-168923637-T-A			Likely benign (Sep 27, 2023)
2-168923642-T-C		Progressive familial intrahepatic cholestasis type 2	Uncertain significance (Aug 13, 2020)
2-168923642-TG-T		Benign recurrent intrahepatic cholestasis type 2	Conflicting classifications of pathogenicity (Jan 11, 2022)
2-168923651-G-A			Likely benign (May 08, 2023)
2-168923661-G-T			Likely benign (Aug 29, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCB11	protein_coding	protein_coding	ENST00000263817	27	108385

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.56e-12	1.00	124592	0	76	124668	0.000305

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.11	631	714	0.883	0.0000370	8645
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00104	0.00103
Ashkenazi Jewish	0.00	0.00
East Asian	0.000232	0.000222
Finnish	0.000186	0.000186
European (Non-Finnish)	0.000182	0.000177
Middle Eastern	0.000232	0.000222
South Asian	0.000573	0.000556
Other	0.000662	0.000660

dbNSFP

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.
• Pathway: Bile secretion - Homo sapiens (human);ABC transporters - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);Statin Pathway - Generalized, Pharmacokinetics;Pravastatin Pathway, Pharmacokinetics;Rosuvastatin Pathway, Pharmacokinetics;Drug Induction of Bile Acid Pathway;Farnesoid X Receptor Pathway;Nuclear Receptors Meta-Pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;multi-drug resistance factors;Metabolism of lipids;Metabolism;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Synthesis of bile acids and bile salts;Recycling of bile acids and salts;Bile acid and bile salt metabolism;Metabolism of steroids;Bile acid biosynthesis (Consensus)

Recessive Scores

• pRec: 0.393

Intolerance Scores

• rvis_EVS: -1.14
• rvis_percentile_EVS: 6.39

Haploinsufficiency Scores

• pHI: 0.109
• hipred: Y
• hipred_score: 0.540
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.176

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Abcb11
• Phenotype: vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: abcb11b
• Affected structure: hepatocyte
• Phenotype tag: abnormal
• Phenotype quality: swollen

Gene ontology

• 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
• Cellular component: plasma membrane;integral component of plasma membrane;membrane;extracellular exosome
• Molecular function: transporter activity;ATP binding;sodium-exporting ATPase activity, phosphorylative mechanism;canalicular bile acid transmembrane transporter activity;bile acid-exporting ATPase activity