MCID: CHL136
MIFTS: 43

Cholestasis, Progressive Familial Intrahepatic, 2

Categories: Genetic diseases, Rare diseases, Liver diseases, Metabolic diseases, Reproductive diseases, Gastrointestinal diseases, Endocrine diseases

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic, 2

MalaCards integrated aliases for Cholestasis, Progressive Familial Intrahepatic, 2:

Name: Cholestasis, Progressive Familial Intrahepatic, 2 57 75 73
Pfic2 57 53 59 75 55
Cholestasis, Progressive Familial Intrahepatic 2 57 76 13
Progressive Familial Intrahepatic Cholestasis Type 2 53 59
Progressive Familial Intrahepatic Cholestasis 2 29 6
Cholestasis, Intrahepatic, Familial, Progressive, Type 2 40
Severe Abcb11 Deficiency 53
Bsep Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
progressive familial intrahepatic cholestasis type 2
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in early infancy
caused by a defect in bile acid transport
genetic heterogeneity, see pfic1


HPO:

32
cholestasis, progressive familial intrahepatic, 2:
Onset and clinical course infantile onset
Mortality/Aging death in childhood
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 601847
Orphanet 59 ORPHA79304
UMLS via Orphanet 74 C1866138 C3489789
ICD10 via Orphanet 34 K76.8
MESH via Orphanet 45 C535934
MeSH 44 D002780
UMLS 73 C3489789

Summaries for Cholestasis, Progressive Familial Intrahepatic, 2

NIH Rare Diseases : 53 Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a rare condition that affects the liver. People with this condition generally develop signs and symptoms during infancy, which may include severe itching, jaundice, failure to thrive, portal hypertension (high blood pressure in the vein that provides blood to the liver) and hepatosplenomegaly (enlarged liver and spleen). PFIC2 generally progresses to liver failure in the first few years of life. Affected people also have an increased risk of developing hepatocellular carcinoma (a form of liver cancer). PFIC2 is caused by change (mutations) in the ABCB11 gene and is inherited in an autosomal recessive manner. Treatment may include ursodeoxycholic acid therapy to prevent liver damage, surgery and/or liver transplantation.

MalaCards based summary : Cholestasis, Progressive Familial Intrahepatic, 2, also known as pfic2, is related to cholestasis, progressive familial intrahepatic, 1 and intrahepatic cholestasis, and has symptoms including diarrhea, icterus and pruritus. An important gene associated with Cholestasis, Progressive Familial Intrahepatic, 2 is ABCB11 (ATP Binding Cassette Subfamily B Member 11), and among its related pathways/superpathways are Hepatic ABC Transporters and Bile secretion. Affiliated tissues include liver and spleen, and related phenotypes are failure to thrive and splenomegaly

UniProtKB/Swiss-Prot : 75 Cholestasis, progressive familial intrahepatic, 2: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood.

Wikipedia : 76 Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions... more...

Description from OMIM: 601847

Related Diseases for Cholestasis, Progressive Familial Intrahepatic, 2

Graphical network of the top 20 diseases related to Cholestasis, Progressive Familial Intrahepatic, 2:



Diseases related to Cholestasis, Progressive Familial Intrahepatic, 2

Symptoms & Phenotypes for Cholestasis, Progressive Familial Intrahepatic, 2

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive
growth retardation

Abdomen Liver:
hepatomegaly
cirrhosis
jaundice
intrahepatic cholestasis
intracanalicular cholestasis shown on biopsy
more
Skin Nails Hair Skin:
pruritus
jaundice

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

AbdomenSpleen:
splenomegaly

Growth Height:
short stature

Abdomen Gastrointestinal:
diarrhea
malabsorption of fat and fat-soluble vitamins

Neoplasia:
increased risk of hepatocellular carcinoma


Clinical features from OMIM:

601847

Human phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 2:

32 (show all 13)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 splenomegaly 32 HP:0001744
3 hepatomegaly 32 HP:0002240
4 short stature 32 HP:0004322
5 pruritus 32 HP:0000989
6 cirrhosis 32 HP:0001394
7 diarrhea 32 HP:0002014
8 intrahepatic cholestasis 32 HP:0001406
9 conjugated hyperbilirubinemia 32 HP:0002908
10 hepatocellular carcinoma 32 HP:0001402
11 elevated alkaline phosphatase 32 HP:0003155
12 fat malabsorption 32 HP:0002630
13 intermittent jaundice 32 HP:0001046

UMLS symptoms related to Cholestasis, Progressive Familial Intrahepatic, 2:


diarrhea, icterus, pruritus

GenomeRNAi Phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 2 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 9.17 ATP8B1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-14 9.17 ABCB11
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.17 ATP8B1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-179 9.17 ABCB11 ATP8B1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.17 ATP8B1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-75 9.17 ABCB11

MGI Mouse Phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 liver/biliary system MP:0005370 8.8 ABCB11 ABCB4 ATP8B1

Drugs & Therapeutics for Cholestasis, Progressive Familial Intrahepatic, 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC 1 or 2 Recruiting NCT03566238 Phase 3 A4250;Placebo

Search NIH Clinical Center for Cholestasis, Progressive Familial Intrahepatic, 2

Genetic Tests for Cholestasis, Progressive Familial Intrahepatic, 2

Genetic tests related to Cholestasis, Progressive Familial Intrahepatic, 2:

# Genetic test Affiliating Genes
1 Progressive Familial Intrahepatic Cholestasis 2 29 ABCB11

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic, 2

MalaCards organs/tissues related to Cholestasis, Progressive Familial Intrahepatic, 2:

41
Liver, Spleen

Publications for Cholestasis, Progressive Familial Intrahepatic, 2

Articles related to Cholestasis, Progressive Familial Intrahepatic, 2:

(show all 16)
# Title Authors Year
1
A Rare BSEP Mutation Associated with a Mild Form of Progressive Familial Intrahepatic Cholestasis Type 2. ( 28425419 )
2017
2
Recurrence of Progressive Familial Intrahepatic Cholestasis Type 2 Phenotype After Living-donor Liver Transplantation: A Case Report. ( 27932171 )
2016
3
Successful pregnancy after ileal exclusion in progressive familial intrahepatic cholestasis type 2. ( 26019043 )
2015
4
Targeted pharmacotherapy in progressive familial intrahepatic cholestasis type 2: Evidence for improvement of cholestasis with 4-phenylbutyrate. ( 25716872 )
2015
5
Retargeting of bile salt export pump and favorable outcome in children with progressive familial intrahepatic cholestasis Type 2. ( 25847299 )
2015
6
Brucella infection in a child with progressive familial intrahepatic cholestasis type 2 who had undergone liver transplantation. ( 26148181 )
2015
7
Improved liver function and relieved pruritus after 4-phenylbutyrate therapy in a patient with progressive familial intrahepatic cholestasis type 2. ( 24530123 )
2014
8
Two Cases of Progressive Familial Intrahepatic Cholestasis Type 2 Presenting with Severe Coagulopathy without Jaundice. ( 24991443 )
2014
9
Clinical utility gene card for: progressive familial intrahepatic cholestasis type 2. ( 23982689 )
2013
10
Successful mutation-specific chaperone therapy with 4-phenylbutyrate in a child with progressive familial intrahepatic cholestasis type 2. ( 22609309 )
2012
11
Discovery and structural development of small molecules that enhance transport activity of bile salt export pump mutant associated with progressive familial intrahepatic cholestasis type 2. ( 22464344 )
2012
12
Relapsing features of bile salt export pump deficiency after liver transplantation in two patients with progressive familial intrahepatic cholestasis type 2. ( 20800306 )
2010
13
Normal levels of serum pancreatic enzymes in patients with progressive familial intrahepatic cholestasis type 2. ( 21140002 )
2010
14
Prenatal diagnosis of progressive familial intrahepatic cholestasis type 2. ( 18853996 )
2008
15
Exocrine pancreatic function in children with progressive familial intrahepatic cholestasis type 2. ( 16641580 )
2006
16
A progressive familial intrahepatic cholestasis type 2 mutation causes an unstable, temperature-sensitive bile salt export pump. ( 14672610 )
2004

Variations for Cholestasis, Progressive Familial Intrahepatic, 2

UniProtKB/Swiss-Prot genetic disease variations for Cholestasis, Progressive Familial Intrahepatic, 2:

75 (show all 12)
# Symbol AA change Variation ID SNP ID
1 ABCB11 p.Glu297Gly VAR_010271 rs11568372
2 ABCB11 p.Val284Leu VAR_013332
3 ABCB11 p.Lys461Glu VAR_013334
4 ABCB11 p.Asp482Gly VAR_013335 rs72549402
5 ABCB11 p.Gly982Arg VAR_013336 rs72549399
6 ABCB11 p.Gly1004Asp VAR_013337
7 ABCB11 p.Arg1153Cys VAR_013338 rs72549395
8 ABCB11 p.Arg1268Gln VAR_013339 rs72549394
9 ABCB11 p.Gly238Val VAR_030388 rs72551306
10 ABCB11 p.Cys336Ser VAR_030390 rs72551305
11 ABCB11 p.Tyr472Cys VAR_073968 rs369860506
12 ABCB11 p.Asp1131Val VAR_073971

ClinVar genetic disease variations for Cholestasis, Progressive Familial Intrahepatic, 2:

6
(show all 50)
# Gene Variation Type Significance SNP ID Assembly Location
1 ABCB11 NM_003742.2(ABCB11): c.1723C> T (p.Arg575Ter) single nucleotide variant Pathogenic rs72549401 GRCh37 Chromosome 2, 169826641: 169826641
2 ABCB11 NM_003742.2(ABCB11): c.1723C> T (p.Arg575Ter) single nucleotide variant Pathogenic rs72549401 GRCh38 Chromosome 2, 168970131: 168970131
3 ABCB11 NM_003742.2(ABCB11): c.890A> G (p.Glu297Gly) single nucleotide variant Pathogenic rs11568372 GRCh37 Chromosome 2, 169847329: 169847329
4 ABCB11 NM_003742.2(ABCB11): c.890A> G (p.Glu297Gly) single nucleotide variant Pathogenic rs11568372 GRCh38 Chromosome 2, 168990819: 168990819
5 ABCB11 NM_003742.2(ABCB11): c.908delG (p.Arg303Serfs) deletion Pathogenic GRCh38 Chromosome 2, 168990801: 168990801
6 ABCB11 NM_003742.2(ABCB11): c.908delG (p.Arg303Serfs) deletion Pathogenic GRCh37 Chromosome 2, 169847311: 169847311
7 ABCB11 NM_003742.2(ABCB11): c.3767_3768insC (p.Val1257Glyfs) insertion Pathogenic rs387907317 GRCh37 Chromosome 2, 169780331: 169780331
8 ABCB11 NM_003742.2(ABCB11): c.3767_3768insC (p.Val1257Glyfs) insertion Pathogenic rs387907317 GRCh38 Chromosome 2, 168923821: 168923821
9 ABCB11 NM_003742.2(ABCB11): c.150+3A> C single nucleotide variant Pathogenic rs387906354 GRCh37 Chromosome 2, 169870810: 169870810
10 ABCB11 NM_003742.2(ABCB11): c.150+3A> C single nucleotide variant Pathogenic rs387906354 GRCh38 Chromosome 2, 169014300: 169014300
11 ABCB11 ABCB11, 5-BP INS, GAGAT insertion Pathogenic
12 ABCB11 NM_003742.2(ABCB11): c.3169C> T (p.Arg1057Ter) single nucleotide variant Pathogenic rs72549397 GRCh37 Chromosome 2, 169788931: 169788931
13 ABCB11 NM_003742.2(ABCB11): c.3169C> T (p.Arg1057Ter) single nucleotide variant Pathogenic rs72549397 GRCh38 Chromosome 2, 168932421: 168932421
14 ABCB11 NM_003742.2(ABCB11): c.2012-8T> G single nucleotide variant Pathogenic rs769910565 GRCh37 Chromosome 2, 169825008: 169825008
15 ABCB11 NM_003742.2(ABCB11): c.2012-8T> G single nucleotide variant Pathogenic rs769910565 GRCh38 Chromosome 2, 168968498: 168968498
16 ABCB11 NM_003742.2(ABCB11): c.908+1G> A single nucleotide variant Pathogenic rs147649016 GRCh37 Chromosome 2, 169847310: 169847310
17 ABCB11 NM_003742.2(ABCB11): c.908+1G> A single nucleotide variant Pathogenic rs147649016 GRCh38 Chromosome 2, 168990800: 168990800
18 ABCB11 NM_003742.2(ABCB11): c.3692G> A (p.Arg1231Gln) single nucleotide variant Pathogenic rs758069019 GRCh37 Chromosome 2, 169781240: 169781240
19 ABCB11 NM_003742.2(ABCB11): c.3692G> A (p.Arg1231Gln) single nucleotide variant Pathogenic rs758069019 GRCh38 Chromosome 2, 168924730: 168924730
20 ABCB11 NM_003742.2(ABCB11): c.1271delA (p.Asn424Metfs) deletion Pathogenic rs886043703 GRCh37 Chromosome 2, 169833124: 169833124
21 ABCB11 NM_003742.2(ABCB11): c.1271delA (p.Asn424Metfs) deletion Pathogenic rs886043703 GRCh38 Chromosome 2, 168976614: 168976614
22 ABCB11 NM_003742.2(ABCB11): c.150+1G> A single nucleotide variant Pathogenic rs886043875 GRCh37 Chromosome 2, 169870812: 169870812
23 ABCB11 NM_003742.2(ABCB11): c.150+1G> A single nucleotide variant Pathogenic rs886043875 GRCh38 Chromosome 2, 169014302: 169014302
24 ABCB11 NM_003742.2(ABCB11): c.1069G> T (p.Gly357Ter) single nucleotide variant Pathogenic rs886043935 GRCh37 Chromosome 2, 169842634: 169842634
25 ABCB11 NM_003742.2(ABCB11): c.1069G> T (p.Gly357Ter) single nucleotide variant Pathogenic rs886043935 GRCh38 Chromosome 2, 168986124: 168986124
26 ABCB11 NM_003742.2(ABCB11): c.1445A> G (p.Asp482Gly) single nucleotide variant Pathogenic rs72549402 GRCh37 Chromosome 2, 169828550: 169828550
27 ABCB11 NM_003742.2(ABCB11): c.1445A> G (p.Asp482Gly) single nucleotide variant Pathogenic rs72549402 GRCh38 Chromosome 2, 168972040: 168972040
28 ABCB11 NM_003742.2(ABCB11): c.22C> T (p.Arg8Ter) single nucleotide variant Pathogenic rs886043986 GRCh37 Chromosome 2, 169874614: 169874614
29 ABCB11 NM_003742.2(ABCB11): c.22C> T (p.Arg8Ter) single nucleotide variant Pathogenic rs886043986 GRCh38 Chromosome 2, 169018104: 169018104
30 ABCB11 NM_003742.2(ABCB11): c.3457C> T (p.Arg1153Cys) single nucleotide variant Pathogenic rs72549395 GRCh37 Chromosome 2, 169783827: 169783827
31 ABCB11 NM_003742.2(ABCB11): c.3457C> T (p.Arg1153Cys) single nucleotide variant Pathogenic rs72549395 GRCh38 Chromosome 2, 168927317: 168927317
32 ABCB11 NC_000002.11: g.169830232_169830305del56 deletion Pathogenic GRCh37 Chromosome 2, 169830232: 169830305
33 ABCB11 NM_003742.2(ABCB11): c.1460G> A (p.Arg487His) single nucleotide variant Likely pathogenic rs188824058 GRCh37 Chromosome 2, 169828535: 169828535
34 ABCB11 NM_003742.2(ABCB11): c.1460G> A (p.Arg487His) single nucleotide variant Likely pathogenic rs188824058 GRCh38 Chromosome 2, 168972025: 168972025
35 ABCB11 NM_003742.2(ABCB11): c.2296G> A (p.Gly766Arg) single nucleotide variant Pathogenic rs763782349 GRCh37 Chromosome 2, 169814521: 169814521
36 ABCB11 NM_003742.2(ABCB11): c.2296G> A (p.Gly766Arg) single nucleotide variant Pathogenic rs763782349 GRCh38 Chromosome 2, 168958011: 168958011
37 ABCB11 NM_003742.2(ABCB11): c.2380C> T (p.Gln794Ter) single nucleotide variant Pathogenic rs1060499579 GRCh37 Chromosome 2, 169801435: 169801435
38 ABCB11 NM_003742.2(ABCB11): c.2380C> T (p.Gln794Ter) single nucleotide variant Pathogenic rs1060499579 GRCh38 Chromosome 2, 168944925: 168944925
39 ABCB11 NM_003742.3(ABCB11): c.1408C> T (p.Arg470Ter) single nucleotide variant Pathogenic rs774824767 GRCh37 Chromosome 2, 169830251: 169830251
40 ABCB11 NM_003742.3(ABCB11): c.1408C> T (p.Arg470Ter) single nucleotide variant Pathogenic rs774824767 GRCh38 Chromosome 2, 168973741: 168973741
41 ABCB11 NM_003742.3(ABCB11): c.1146_1166del21 (p.Phe383_Ala389del) deletion Uncertain significance GRCh37 Chromosome 2, 169836407: 169836427
42 ABCB11 NM_003742.3(ABCB11): c.1146_1166del21 (p.Phe383_Ala389del) deletion Uncertain significance GRCh38 Chromosome 2, 168979897: 168979917
43 ABCB11 NM_003742.3(ABCB11): c.2782C> T (p.Arg928Ter) single nucleotide variant Pathogenic rs756529333 GRCh37 Chromosome 2, 169792772: 169792772
44 ABCB11 NM_003742.3(ABCB11): c.2782C> T (p.Arg928Ter) single nucleotide variant Pathogenic rs756529333 GRCh38 Chromosome 2, 168936262: 168936262
45 ABCB11 NM_003742.3(ABCB11): c.1631delT (p.Leu544Argfs) deletion Pathogenic GRCh37 Chromosome 2, 169828364: 169828364
46 ABCB11 NM_003742.3(ABCB11): c.1631delT (p.Leu544Argfs) deletion Pathogenic GRCh38 Chromosome 2, 168971854: 168971854
47 ABCB11 NM_003742.3(ABCB11): c.3268C> T (p.Arg1090Ter) single nucleotide variant Pathogenic rs72549396 GRCh37 Chromosome 2, 169787318: 169787318
48 ABCB11 NM_003742.3(ABCB11): c.3268C> T (p.Arg1090Ter) single nucleotide variant Pathogenic rs72549396 GRCh38 Chromosome 2, 168930808: 168930808
49 ABCB11 NM_003742.3(ABCB11): c.2494C> T (p.Arg832Cys) single nucleotide variant Likely pathogenic rs772294884 GRCh37 Chromosome 2, 169801231: 169801231
50 ABCB11 NM_003742.3(ABCB11): c.2494C> T (p.Arg832Cys) single nucleotide variant Likely pathogenic rs772294884 GRCh38 Chromosome 2, 168944721: 168944721

Expression for Cholestasis, Progressive Familial Intrahepatic, 2

Search GEO for disease gene expression data for Cholestasis, Progressive Familial Intrahepatic, 2.

Pathways for Cholestasis, Progressive Familial Intrahepatic, 2

Pathways related to Cholestasis, Progressive Familial Intrahepatic, 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.35 ABCB11 ABCB4
2 11.01 ABCB11 ABCB4
3 10.5 ABCB11 ABCB4
4 9.9 ABCB11 ABCB4

GO Terms for Cholestasis, Progressive Familial Intrahepatic, 2

Cellular components related to Cholestasis, Progressive Familial Intrahepatic, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of plasma membrane GO:0005887 9.43 ABCB11 ABCB4 ATP8B1
2 apical plasma membrane GO:0016324 9.32 ABCB4 ATP8B1
3 apical part of cell GO:0045177 9.16 ABCB11 ABCB4
4 brush border membrane GO:0031526 8.96 ABCB4 ATP8B1
5 intercellular canaliculus GO:0046581 8.62 ABCB11 ABCB4

Biological processes related to Cholestasis, Progressive Familial Intrahepatic, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid transport GO:0006869 9.26 ABCB4 ATP8B1
2 bile acid and bile salt transport GO:0015721 9.16 ABCB11 ATP8B1
3 drug transmembrane transport GO:0006855 8.96 ABCB4 ATP8B1
4 phospholipid translocation GO:0045332 8.62 ABCB4 ATP8B1

Molecular functions related to Cholestasis, Progressive Familial Intrahepatic, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATPase activity GO:0016887 9.16 ABCB11 ABCB4
2 ATP binding GO:0005524 9.13 ABCB11 ABCB4 ATP8B1
3 ATPase activity, coupled to transmembrane movement of substances GO:0042626 8.62 ABCB11 ABCB4

Sources for Cholestasis, Progressive Familial Intrahepatic, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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