BRIC2
MCID: CHL118
MIFTS: 45

Cholestasis, Benign Recurrent Intrahepatic, 2 (BRIC2)

Categories: Cancer diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Cholestasis, Benign Recurrent Intrahepatic, 2

MalaCards integrated aliases for Cholestasis, Benign Recurrent Intrahepatic, 2:

Name: Cholestasis, Benign Recurrent Intrahepatic, 2 56 73 13
Benign Recurrent Intrahepatic Cholestasis 2 12 52 29 6 15
Bric2 56 12 52 58 73
Cholestasis, Benign Recurrent Intrahepatic 2 52 71
Bric Type 2 12 58
Cholestasis, Intrahepatic, Recurrent, Benign, Type 2 39
Benign Recurrent Intrahepatic Cholestasis Type 2 58
Recurrent Familial Intrahepatic Cholestasis 2 52
Mild Abcb11 Deficiency 52

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
disease-free intervals can last weeks to years during which there is no clinical or biochemical evidence of cholestasis
onset in first 2 decades
precipitating factors include viral illness and pregnancy
allelic disorder to progressive familial intrahepatic cholestasis-2 (pfic2, )


HPO:

31
cholestasis, benign recurrent intrahepatic, 2:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare hepatic diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0070232
OMIM 56 605479
OMIM Phenotypic Series 56 PS243300
MeSH 43 D002780
MESH via Orphanet 44 C535931
ICD10 via Orphanet 33 K83.1
UMLS via Orphanet 72 C2608083 C3489789
Orphanet 58 ORPHA99961
MedGen 41 C2608083
UMLS 71 C2608083 C3489789

Summaries for Cholestasis, Benign Recurrent Intrahepatic, 2

UniProtKB/Swiss-Prot : 73 Cholestasis, benign recurrent intrahepatic, 2: 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.

MalaCards based summary : Cholestasis, Benign Recurrent Intrahepatic, 2, also known as benign recurrent intrahepatic cholestasis 2, is related to atp8b1 deficiency and cholelithiasis. An important gene associated with Cholestasis, Benign Recurrent Intrahepatic, 2 is ABCB11 (ATP Binding Cassette Subfamily B Member 11), and among its related pathways/superpathways are Metabolism and Synthesis of bile acids and bile salts. Affiliated tissues include liver and pancreas, and related phenotypes are intrahepatic cholestasis and hepatomegaly

Disease Ontology : 12 A benign recurrent intrahepatic cholestasis characterized by autosomal recessive inheritance that has material basis in mutation in the ABCB11 gene on chromosome 2q31.

OMIM : 56 Benign recurrent intrahepatic cholestasis is characterized by intermittent episodes of cholestasis without progression to liver failure. The cholestatic attacks vary in severity and duration and patients are asymptomatic between episodes, both clinically and biochemically (van Mil et al., 2004). (605479)

Related Diseases for Cholestasis, Benign Recurrent Intrahepatic, 2

Diseases in the Familial Intrahepatic Cholestasis family:

Cholestasis, Progressive Familial Intrahepatic, 1 Cholestasis, Benign Recurrent Intrahepatic, 1
Cholestasis, Progressive Familial Intrahepatic, 2 Cholestasis, Progressive Familial Intrahepatic, 3
Cholestasis, Benign Recurrent Intrahepatic, 2 Cholestasis, Progressive Familial Intrahepatic, 4
Cholestasis, Progressive Familial Intrahepatic, 5 Progressive Familial Intrahepatic Cholestasis
Myo5b-Related Progressive Familial Intrahepatic Cholestasis

Diseases related to Cholestasis, Benign Recurrent Intrahepatic, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 45)
# Related Disease Score Top Affiliating Genes
1 atp8b1 deficiency 30.4 NR1H4 ATP8B1 ABCB11
2 cholelithiasis 29.3 NR1H4 CYP7A1 ABCG5 ABCB4
3 familial intrahepatic cholestasis 28.6 TJP2 SLC10A2 NR1H4 ATP8B1 ABCC2 ABCB4
4 cholestasis, benign recurrent intrahepatic, 1 28.1 TJP2 SLC25A13 SLC10A2 SLC10A1 NR1H4 CYP7A1
5 progressive familial intrahepatic cholestasis 26.8 TJP2 SLC10A2 SLC10A1 NR1H4 CYP7A1 ATP8B1
6 cholestasis 26.7 TJP2 SLC25A13 SLC10A2 SLC10A1 NR1H4 CYP7A1
7 cholestasis, progressive familial intrahepatic, 2 26.7 TJP2 SLC10A2 SLC10A1 NR1H4 CYP7A1 ATP8B1
8 cholangitis 10.2 NR1H4 ABCB4 ABCB11
9 liver cirrhosis 10.2
10 growth hormone deficiency 10.2
11 autosomal dominant non-syndromic intellectual disability 3 10.2 ABCB4 ABCB11
12 autosomal recessive disease 10.1
13 hepatitis a 10.1
14 chronic cholangitis 10.1 ATP8B1 ABCB4
15 caroli disease 10.0 ATP8B1 ABCB4
16 urea cycle disorder 9.9 SLC25A13 ATP8B1 ABCB11
17 sclerosing cholangitis 9.8 NR1H4 ABCC2 ABCB4 ABCB11
18 pericholangitis 9.8 SLC10A2 SLC10A1 ABCB4 ABCB11
19 functional diarrhea 9.8 SLC10A2 NR1H4 CYP7A1
20 dubin-johnson syndrome 9.8 ATP8B1 ABCC3 ABCC2 ABCB11
21 bile duct cysts 9.8 SLC25A13 ATP8B1 ABCB4 ABCB11
22 alagille syndrome 1 9.7 SLC25A13 ATP8B1 ABCB4 ABCB11
23 ornithine transcarbamylase deficiency, hyperammonemia due to 9.7 SLC25A13 ABCB11
24 bile acid synthesis defect, congenital, 2 9.6 SLC10A1 NR1H4 CYP7A1 ABCB11
25 bile acid synthesis defect, congenital, 3 9.6 SLC25A13 NR1H4 CYP7A1
26 obstructive jaundice 9.6 SLC25A13 ABCC3 ABCC2
27 bilirubin metabolic disorder 9.6 ATP8B1 ABCC3 ABCC2 ABCB4 ABCB11
28 cholestasis, progressive familial intrahepatic, 5 9.5 TJP2 NR1H4 ATP8B1 ABCB11
29 hypercholesterolemia, familial, 1 9.5 NR1H4 CYP7A1 ABCG5
30 autoimmune disease of urogenital tract 9.5 SLC10A1 NR1H4 CYP7A1 ABCB4 ABCB11
31 biliary atresia 9.4 SLC10A2 SLC10A1 NR1H4 ATP8B1 ABCB4 ABCB11
32 intrahepatic cholestasis of pregnancy 9.4 NR1H4 ATP8B1 ABCC3 ABCC2 ABCB4 ABCB11
33 cholestasis, progressive familial intrahepatic, 4 9.3 TJP2 SLC10A2 ATP8B1 ABCB4 ABCB11
34 gallbladder disease 9.2 NR1H4 CYP7A1 ABCG5 ABCB4 ABCB11
35 cholestasis, intrahepatic, of pregnancy, 1 9.1 SLC25A13 SLC10A2 NR1H4 ATP8B1 ABCC2 ABCB4
36 sitosterolemia 9.1 CYP7A1 ATP8B1 ABCG5 ABCC2 ABCB4 ABCB11
37 extrahepatic cholestasis 9.0 SLC10A1 NR1H4 CYP7A1 ABCC3 ABCC2 ABCB4
38 primary biliary cirrhosis 8.9 SLC10A1 NR1H4 CYP7A1 ABCC3 ABCC2 ABCB4
39 cholangitis, primary sclerosing 8.8 SLC10A2 SLC10A1 NR1H4 CYP7A1 ATP8B1 ABCC2
40 liver disease 8.4 TJP2 SLC25A13 SLC10A1 NR1H4 ATP8B1 ABCC2
41 leber congenital amaurosis 8.2 SLC10A2 SLC10A1 NR1H4 CYP7A1 ABCG5 ABCC3
42 cholestasis, progressive familial intrahepatic, 3 8.1 TJP2 SLC10A2 SLC10A1 NR1H4 ATP8B1 ABCG5
43 biliary tract disease 8.1 SLC25A13 SLC10A2 SLC10A1 NR1H4 CYP7A1 ATP8B1
44 bile duct disease 8.1 SLC25A13 SLC10A2 SLC10A1 NR1H4 CYP7A1 ATP8B1
45 cholestasis, progressive familial intrahepatic, 1 7.7 TJP2 SLC10A2 SLC10A1 NR1H4 CYP7A1 ATP8B1

Graphical network of the top 20 diseases related to Cholestasis, Benign Recurrent Intrahepatic, 2:



Diseases related to Cholestasis, Benign Recurrent Intrahepatic, 2

Symptoms & Phenotypes for Cholestasis, Benign Recurrent Intrahepatic, 2

Human phenotypes related to Cholestasis, Benign Recurrent Intrahepatic, 2:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 intrahepatic cholestasis 31 occasional (7.5%) HP:0001406
2 hepatomegaly 31 HP:0002240
3 pruritus 31 HP:0000989
4 cholelithiasis 31 HP:0001081
5 jaundice 31 HP:0000952
6 conjugated hyperbilirubinemia 31 HP:0002908
7 elevated alkaline phosphatase 31 HP:0003155

Symptoms via clinical synopsis from OMIM:

56
Abdomen Liver:
hepatomegaly
cholelithiasis
jaundice, episodic
progression to end-stage liver disease does not occur
intrahepatic cholestasis, episodic, recurrent, may be permanent in some patients later in life
more
Skin Nails Hair Skin:
jaundice, episodic
pruritus, episodic

Laboratory Abnormalities:
conjugated hyperbilirubinemia
increased alkaline phosphatase
normal or mildly increased serum gamma-ggt
increased serum bile acids

Clinical features from OMIM:

605479

MGI Mouse Phenotypes related to Cholestasis, Benign Recurrent Intrahepatic, 2:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.85 ABCB11 ABCB4 ABCG5 ATP8B1 CYP7A1 NR1H4
2 digestive/alimentary MP:0005381 9.73 ABCB4 ABCG5 CYP7A1 NR1H4 NR5A2 SLC10A2
3 homeostasis/metabolism MP:0005376 9.7 ABCB11 ABCB4 ABCC2 ABCC3 ABCG5 ATP8B1
4 liver/biliary system MP:0005370 9.36 ABCB11 ABCB4 ABCC2 ABCC3 ABCG5 ATP8B1

Drugs & Therapeutics for Cholestasis, Benign Recurrent Intrahepatic, 2

Search Clinical Trials , NIH Clinical Center for Cholestasis, Benign Recurrent Intrahepatic, 2

Genetic Tests for Cholestasis, Benign Recurrent Intrahepatic, 2

Genetic tests related to Cholestasis, Benign Recurrent Intrahepatic, 2:

# Genetic test Affiliating Genes
1 Benign Recurrent Intrahepatic Cholestasis 2 29

Anatomical Context for Cholestasis, Benign Recurrent Intrahepatic, 2

MalaCards organs/tissues related to Cholestasis, Benign Recurrent Intrahepatic, 2:

40
Liver, Pancreas

Publications for Cholestasis, Benign Recurrent Intrahepatic, 2

Articles related to Cholestasis, Benign Recurrent Intrahepatic, 2:

(show all 15)
# Title Authors PMID Year
1
Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis. 61 56 6
16039748 2005
2
Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11. 56 6
15300568 2004
3
ATP8B1 Deficiency 6
20301474 2001
4
Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. 6
10579978 1999
5
A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. 6
9806540 1998
6
Benign Recurrent Intrahepatic Cholestasis Type 2 in Siblings with Novel ABCB11 Mutations. 61
30899697 2019
7
A Physiology-Based Model of Human Bile Acid Metabolism for Predicting Bile Acid Tissue Levels After Drug Administration in Healthy Subjects and BRIC Type 2 Patients. 61
31611804 2019
8
Successful treatment with 4-phenylbutyrate in a patient with benign recurrent intrahepatic cholestasis type 2 refractory to biliary drainage and bilirubin absorption. 61
26223708 2016
9
Biosynthesis and trafficking of the bile salt export pump, BSEP: therapeutic implications of BSEP mutations. 61
23685087 2014
10
The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease. 61
20422495 2010
11
Characterization of apoptotic activities during chlamydia trachomatis infection in primary cervical epithelial cells. 61
20840054 2010
12
Phenotypic differences in PFIC2 and BRIC2 correlate with protein stability of mutant Bsep and impaired taurocholate secretion in MDCK II cells. 61
17947449 2008
13
Gradual improvement of liver function after administration of ursodeoxycholic acid in an infant with a novel ABCB11 gene mutation with phenotypic continuum between BRIC2 and PFIC2. 61
18049162 2007
14
Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases. 61
17855769 2007
15
A patient with novel ABCB11 gene mutations with phenotypic transition between BRIC2 and PFIC2. 61
16290310 2006

Variations for Cholestasis, Benign Recurrent Intrahepatic, 2

ClinVar genetic disease variations for Cholestasis, Benign Recurrent Intrahepatic, 2:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ABCB11 NM_003742.4(ABCB11):c.890A>G (p.Glu297Gly)SNV Pathogenic 6590 rs11568372 2:169847329-169847329 2:168990819-168990819
2 ABCB11 NM_003742.4(ABCB11):c.1295G>C (p.Arg432Thr)SNV Pathogenic 6595 rs121908935 2:169833100-169833100 2:168976590-168976590
3 ABCB11 NM_003742.4(ABCB11):c.2380C>T (p.Gln794Ter)SNV Pathogenic 417884 rs1060499579 2:169801435-169801435 2:168944925-168944925
4 ABCB11 NM_003742.4(ABCB11):c.2012-8T>GSNV Pathogenic/Likely pathogenic 284637 rs769910565 2:169825008-169825008 2:168968498-168968498
5 ABCB11 NM_003742.4(ABCB11):c.1460G>A (p.Arg487His)SNV Conflicting interpretations of pathogenicity 290081 rs188824058 2:169828535-169828535 2:168972025-168972025
6 ABCB11 NM_003742.4(ABCB11):c.3326T>C (p.Leu1109Pro)SNV Uncertain significance 522890 rs1553545883 2:169787260-169787260 2:168930750-168930750
7 ABCB11 NM_003742.4(ABCB11):c.2125G>A (p.Glu709Lys)SNV Uncertain significance 286699 rs201800225 2:169820769-169820769 2:168964259-168964259

UniProtKB/Swiss-Prot genetic disease variations for Cholestasis, Benign Recurrent Intrahepatic, 2:

73
# Symbol AA change Variation ID SNP ID
1 ABCB11 p.Glu297Gly VAR_010271 rs11568372
2 ABCB11 p.Glu186Gly VAR_030386 rs72551307
3 ABCB11 p.Arg432Thr VAR_030391 rs121908935
4 ABCB11 p.Ala570Thr VAR_030392 rs886043807
5 ABCB11 p.Thr923Pro VAR_030394 rs777469571
6 ABCB11 p.Ala926Pro VAR_030395 rs72549400
7 ABCB11 p.Arg1050Cys VAR_030396 rs72549398
8 ABCB11 p.Arg1128His VAR_030397 rs756220860

Expression for Cholestasis, Benign Recurrent Intrahepatic, 2

Search GEO for disease gene expression data for Cholestasis, Benign Recurrent Intrahepatic, 2.

Pathways for Cholestasis, Benign Recurrent Intrahepatic, 2

Pathways related to Cholestasis, Benign Recurrent Intrahepatic, 2 according to GeneCards Suite gene sharing:

(show all 16)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.84 SLC25A13 SLC10A2 SLC10A1 NR1H4 CYP7A1 ABCG5
2
Show member pathways
12.04 SLC10A2 SLC10A1 NR1H4 CYP7A1 ABCC3 ABCB11
3
Show member pathways
11.76 SLC10A1 ABCC2 ABCB4 ABCB11
4
Show member pathways
11.73 CYP7A1 ABCG5 ABCB11
5
Show member pathways
11.67 ABCC3 ABCC2 ABCB11
6 11.13 SLC10A2 SLC10A1 NR1H4 CYP7A1 ABCG5 ABCC3
7 11.06 ABCC3 ABCC2
8 11.04 ABCC3 ABCC2
9 11.04 NR1H4 CYP7A1 ABCG5 ABCC3 ABCC2 ABCB4
10 10.93 SLC10A1 NR1H4 CYP7A1 ABCB4 ABCB11
11 10.89 ABCC3 ABCC2
12 10.86 SLC10A1 NR1H4 CYP7A1 ABCC3 ABCC2 ABCB11
13
Show member pathways
10.81 ABCC3 ABCC2
14 10.75 ABCC3 ABCC2
15 10.63 ABCC3 ABCC2
16 10.4 ABCC3 ABCC2

GO Terms for Cholestasis, Benign Recurrent Intrahepatic, 2

Cellular components related to Cholestasis, Benign Recurrent Intrahepatic, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 10.07 SLC25A13 SLC10A2 SLC10A1 CYP7A1 ATP8B1 ABCG5
2 membrane GO:0016020 10.03 TJP2 SLC25A13 SLC10A2 SLC10A1 FRMPD2 CYP7A1
3 plasma membrane GO:0005886 10.02 TJP2 SLC10A2 SLC10A1 FRMPD2 ATP8B1 ABCG5
4 integral component of plasma membrane GO:0005887 9.61 SLC25A13 SLC10A2 SLC10A1 ATP8B1 ABCG5 ABCC3
5 apical plasma membrane GO:0016324 9.55 SLC10A2 ATP8B1 ABCG5 ABCC2 ABCB4
6 intercellular canaliculus GO:0046581 8.8 ABCC2 ABCB4 ABCB11

Biological processes related to Cholestasis, Benign Recurrent Intrahepatic, 2 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 lipid transport GO:0006869 9.65 ATP8B1 ABCG5 ABCB4
2 cholesterol homeostasis GO:0042632 9.62 NR5A2 NR1H4 CYP7A1 ABCG5
3 transmembrane transport GO:0055085 9.56 SLC25A13 SLC10A2 SLC10A1 ABCG5 ABCC3 ABCC2
4 lipid homeostasis GO:0055088 9.54 NR1H4 ABCB4
5 intracellular receptor signaling pathway GO:0030522 9.52 NR5A2 NR1H4
6 bile acid biosynthetic process GO:0006699 9.51 CYP7A1 ABCB11
7 phospholipid translocation GO:0045332 9.49 ATP8B1 ABCB4
8 organic anion transport GO:0015711 9.46 ABCC3 ABCC2
9 xenobiotic transport GO:0042908 9.43 ABCC3 ABCC2
10 bile acid metabolic process GO:0008206 9.43 NR5A2 NR1H4 ATP8B1
11 drug transmembrane transport GO:0006855 9.4 ATP8B1 ABCC2
12 regulation of bile acid biosynthetic process GO:0070857 9.37 NR1H4 CYP7A1
13 canalicular bile acid transport GO:0015722 9.33 ABCC3 ABCC2 ABCB11
14 bile acid and bile salt transport GO:0015721 9.17 SLC10A2 SLC10A1 NR1H4 ATP8B1 ABCC3 ABCC2

Molecular functions related to Cholestasis, Benign Recurrent Intrahepatic, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.88 ATP8B1 ABCG5 ABCC3 ABCC2 ABCB4 ABCB11
2 transmembrane transporter activity GO:0022857 9.61 SLC25A13 ABCC3 ABCC2
3 xenobiotic transmembrane transporter activity GO:0042910 9.37 ABCC3 ABCC2
4 ATPase activity GO:0016887 9.35 ABCG5 ABCC3 ABCC2 ABCB4 ABCB11
5 organic anion transmembrane transporter activity GO:0008514 9.32 ABCC3 ABCC2
6 bile acid:sodium symporter activity GO:0008508 9.26 SLC10A2 SLC10A1
7 bile acid-exporting ATPase activity GO:0015432 9.16 ABCC3 ABCB11
8 ATPase activity, coupled to transmembrane movement of substances GO:0042626 9.02 ABCG5 ABCC3 ABCC2 ABCB4 ABCB11

Sources for Cholestasis, Benign Recurrent Intrahepatic, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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