BRIC2
MCID: CHL118
MIFTS: 43

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 57 74 13
Benign Recurrent Intrahepatic Cholestasis 2 12 53 29 6 15
Bric2 57 12 53 59 74
Cholestasis, Benign Recurrent Intrahepatic 2 53 72
Bric Type 2 12 59
Cholestasis, Intrahepatic, Recurrent, Benign, Type 2 40
Benign Recurrent Intrahepatic Cholestasis Type 2 59
Recurrent Familial Intrahepatic Cholestasis 2 53
Mild Abcb11 Deficiency 53

Characteristics:

OMIM:

57
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:

32
cholestasis, benign recurrent intrahepatic, 2:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0070232
MeSH 44 D002780
MESH via Orphanet 45 C535931
ICD10 via Orphanet 34 K83.1
UMLS via Orphanet 73 C2608083 C3489789
Orphanet 59 ORPHA99961
MedGen 42 C2608083
UMLS 72 C2608083 C3489789

Summaries for Cholestasis, Benign Recurrent Intrahepatic, 2

UniProtKB/Swiss-Prot : 74 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 cholestasis, benign recurrent intrahepatic, 1 and cholestasis, progressive familial intrahepatic, 2. 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 PI3K-Akt signaling pathway and TNFR1 Pathway. 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 : 57 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

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

(show all 27)
# Related Disease Score Top Affiliating Genes
1 cholestasis, benign recurrent intrahepatic, 1 33.0 ATP8B1 ABCB11
2 cholestasis, progressive familial intrahepatic, 2 31.2 ATP8B1 ABCB11
3 atp8b1 deficiency 30.8 ATP8B1 ABCB11
4 progressive familial intrahepatic cholestasis 30.6 ATP8B1 ABCB11
5 cholestasis, progressive familial intrahepatic, 4 10.4 ATP8B1 ABCB11
6 cholestasis, progressive familial intrahepatic, 3 10.4 ATP8B1 ABCB11
7 cholestasis 10.3
8 alagille syndrome 1 10.3 ATP8B1 ABCB11
9 cholestasis, progressive familial intrahepatic, 1 10.3 ATP8B1 ABCB11
10 bile duct disease 10.2 ATP8B1 ABCB11
11 liver cirrhosis 10.2
12 growth hormone deficiency 10.2
13 familial intrahepatic cholestasis 10.2
14 autosomal recessive disease 10.1
15 cholelithiasis 10.1
16 steatorrhea 10.1
17 hepatitis a 10.1
18 biliary tract disease 10.1 ATP8B1 ABCB11
19 caspase 8 deficiency 10.1 CASP8 CASP10
20 juvenile amyotrophic lateral sclerosis 10.0 CASP8 CASP10
21 cowpox 10.0 CASP8 CASP1
22 chlamydia 9.7 MCL1 CASP1
23 dystrophinopathies 9.7 CASP9 CASP8
24 cardiomyopathy, familial hypertrophic, 1 9.7 CASP10 CASP1
25 chronic mountain sickness 9.7 CASP9 CASP8
26 lymphoma, non-hodgkin, familial 9.5 MCL1 CASP8 CASP10
27 myeloma, multiple 9.1 MCL1 CASP9 CASP8

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:

32 (show all 7)
# Description HPO Frequency HPO Source Accession
1 intrahepatic cholestasis 32 occasional (7.5%) HP:0001406
2 hepatomegaly 32 HP:0002240
3 pruritus 32 HP:0000989
4 cholelithiasis 32 HP:0001081
5 jaundice 32 HP:0000952
6 conjugated hyperbilirubinemia 32 HP:0002908
7 elevated alkaline phosphatase 32 HP:0003155

Symptoms via clinical synopsis from OMIM:

57
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

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.7 ATP8B1 CASP1 CASP8 CASP9 MCL1 TRADD
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.7 ATP8B1 CASP1 CASP8 CASP9 MCL1 TRADD

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 ABCB11

Anatomical Context for Cholestasis, Benign Recurrent Intrahepatic, 2

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

41
Liver, Pancreas

Publications for Cholestasis, Benign Recurrent Intrahepatic, 2

Articles related to Cholestasis, Benign Recurrent Intrahepatic, 2:

(show all 14)
# Title Authors PMID Year
1
Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis. 38 8 71
16039748 2005
2
Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11. 8 71
15300568 2004
3
ATP8B1 Deficiency 71
20301474 2001
4
Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. 71
10579978 1999
5
A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. 71
9806540 1998
6
Benign Recurrent Intrahepatic Cholestasis Type 2 in Siblings with Novel ABCB11 Mutations. 38
30899697 2019
7
Successful treatment with 4-phenylbutyrate in a patient with benign recurrent intrahepatic cholestasis type 2 refractory to biliary drainage and bilirubin absorption. 38
26223708 2016
8
Biosynthesis and trafficking of the bile salt export pump, BSEP: therapeutic implications of BSEP mutations. 38
23685087 2014
9
The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease. 38
20422495 2010
10
Characterization of apoptotic activities during chlamydia trachomatis infection in primary cervical epithelial cells. 38
20840054 2010
11
Phenotypic differences in PFIC2 and BRIC2 correlate with protein stability of mutant Bsep and impaired taurocholate secretion in MDCK II cells. 38
17947449 2008
12
Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases. 38
17855769 2007
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. 38
18049162 2007
14
A patient with novel ABCB11 gene mutations with phenotypic transition between BRIC2 and PFIC2. 38
16290310 2006

Variations for Cholestasis, Benign Recurrent Intrahepatic, 2

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

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

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

74
# 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 40)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.79 TRADD MCL1 CASP9 CASP8
2
Show member pathways
12.78 TRADD CASP9 CASP8 CASP10 CASP1
3
Show member pathways
12.76 TRADD CASP9 CASP8 CASP10
4
Show member pathways
12.73 TRADD CASP9 CASP8 CASP10 CASP1
5 12.61 TRADD CASP9 CASP8 CASP1
6
Show member pathways
12.6 TRADD CASP8 CASP10 CASP1
7
Show member pathways
12.53 CASP9 CASP8 CASP10 CASP1
8
Show member pathways
12.52 TRADD MCL1 CASP9 CASP8
9
Show member pathways
12.36 TRADD CASP9 CASP8 CASP10 CASP1
10
Show member pathways
12.33 TRADD MCL1 CASP9 CASP8 CASP10 CASP1
11
Show member pathways
12.32 TRADD CASP9 CASP8 CASP10 CASP1
12
Show member pathways
12.26 CASP9 CASP8 CASP10
13
Show member pathways
12.16 TRADD CASP8 CASP10
14
Show member pathways
12.14 TRADD CASP9 CASP8 CASP10
15
Show member pathways
12.06 TRADD CASP8 CASP1
16 12.05 TRADD CASP9 CASP8 CASP10
17
Show member pathways
12.03 CASP9 CASP8 CASP10 CASP1
18 12.01 TRADD CASP9 CASP8
19
Show member pathways
11.98 TRADD CASP9 CASP8
20 11.92 MCL1 CASP10 CASP1
21
Show member pathways
11.91 TRADD CASP9 CASP8 CASP10 CASP1
22
Show member pathways
11.85 CASP9 CASP8 CASP1
23 11.83 TRADD CASP8 CASP10
24 11.82 CASP9 CASP8 CASP10 CASP1
25
Show member pathways
11.77 CASP9 CASP8 CASP10 CASP1
26
Show member pathways
11.69 MCL1 CASP9 CASP8
27 11.69 CASP9 CASP8 CASP10 CASP1
28
Show member pathways
11.68 CASP9 CASP8 CASP10
29 11.62 TRADD MCL1 CASP9 CASP8 CASP1
30 11.5 CASP9 CASP8
31 11.48 CASP9 CASP8 CASP1
32 11.46 TRADD CASP8 CASP10
33
Show member pathways
11.37 CASP9 CASP8
34 11.34 CASP9 CASP8
35 11.32 TRADD CASP8
36 11.31 CASP9 CASP8 CASP1
37 11.3 CASP9 CASP8
38
Show member pathways
11.3 MCL1 CASP9 CASP8
39 11.26 CASP9 CASP8 CASP10
40
Show member pathways
11.11 TRADD CASP9 CASP8 CASP10 CASP1

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 death-inducing signaling complex GO:0031264 9.26 TRADD CASP8
2 ripoptosome GO:0097342 9.16 CASP8 CASP10
3 protein-containing complex GO:0032991 9.02 TRADD NAT9 CASP9 CASP8 CASP1
4 CD95 death-inducing signaling complex GO:0031265 8.96 CASP8 CASP10

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

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 proteolysis GO:0006508 9.87 CASP9 CASP8 CASP10 CASP1
2 apoptotic process GO:0006915 9.63 TRADD MCL1 CASP9 CASP8 CASP10 CASP1
3 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 9.62 TRADD CASP8 CASP10 CASP1
4 intrinsic apoptotic signaling pathway in response to DNA damage GO:0008630 9.58 MCL1 CASP9
5 extrinsic apoptotic signaling pathway GO:0097191 9.58 TRADD CASP8
6 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902042 9.56 TRADD CASP8
7 extrinsic apoptotic signaling pathway via death domain receptors GO:0008625 9.55 TRADD CASP8
8 extrinsic apoptotic signaling pathway in absence of ligand GO:0097192 9.54 MCL1 CASP9
9 apoptotic signaling pathway GO:0097190 9.54 CASP8 CASP10 CASP1
10 response to antibiotic GO:0046677 9.52 CASP9 CASP8
11 regulation of tumor necrosis factor-mediated signaling pathway GO:0010803 9.51 TRADD CASP8
12 bile acid and bile salt transport GO:0015721 9.49 ATP8B1 ABCB11
13 regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902041 9.48 TRADD CASP8
14 regulation of response to DNA damage stimulus GO:2001020 9.46 MCL1 CASP9
15 death-inducing signaling complex assembly GO:0071550 9.43 TRADD CASP8
16 execution phase of apoptosis GO:0097194 9.43 CASP8 CASP10 CASP1
17 response to cobalt ion GO:0032025 9.4 CASP9 CASP8
18 regulation of apoptotic process GO:0042981 9.35 MCL1 CASP9 CASP8 CASP10 CASP1
19 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006919 9.02 TRADD CASP9 CASP8 CASP10 CASP1

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

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.73 CASP9 CASP8 CASP10 CASP1
2 peptidase activity GO:0008233 9.67 CASP9 CASP8 CASP10 CASP1
3 cysteine-type peptidase activity GO:0008234 9.56 CASP9 CASP8 CASP10 CASP1
4 cysteine-type endopeptidase activity GO:0004197 9.46 CASP9 CASP8 CASP10 CASP1
5 tumor necrosis factor receptor binding GO:0005164 9.4 TRADD CASP8
6 death effector domain binding GO:0035877 9.32 CASP8 CASP10
7 cysteine-type endopeptidase activity involved in apoptotic process GO:0097153 9.26 CASP9 CASP8 CASP10 CASP1
8 cysteine-type endopeptidase activity involved in apoptotic signaling pathway GO:0097199 8.92 CASP9 CASP8 CASP10 CASP1

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 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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