MCID: CHL081
MIFTS: 45

Cholestasis, Progressive Familial Intrahepatic 2

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

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic 2

MalaCards integrated aliases for Cholestasis, Progressive Familial Intrahepatic 2:

Name: Cholestasis, Progressive Familial Intrahepatic 2 54 13
Pfic2 50 24 56 71 52
Progressive Familial Intrahepatic Cholestasis Type 2 50 56
Cholestasis, Progressive Familial Intrahepatic, 2 71 69
Progressive Familial Intrahepatic Cholestasis, Type 2 24
Progressive Familial Intrahepatic Cholestasis 2 29
Severe Abcb11 Deficiency 50
Bsep Deficiency 56
Pfic-2 24

Characteristics:

Orphanet epidemiological data:

56
progressive familial intrahepatic cholestasis type 2
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

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


HPO:

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


Classifications:



Summaries for Cholestasis, Progressive Familial Intrahepatic 2

NIH Rare Diseases : 50 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. last updated: 11/4/2015

MalaCards based summary : Cholestasis, Progressive Familial Intrahepatic 2, also known as pfic2, is related to cholestasis, progressive familial intrahepatic 1 and cholestasis, and has symptoms including short stature, failure to thrive and diarrhea. 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. The drugs Bile Acids and Salts and Liver Extracts have been mentioned in the context of this disorder. Affiliated tissues include liver and spleen, and related phenotypes are Downregulation of NF-kappaB pathway after LMP1 stimulation and Downregulation of NF-kappaB pathway after TNFalpha stimulation

UniProtKB/Swiss-Prot : 71 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.

Description from OMIM: 601847

Related Diseases for Cholestasis, Progressive Familial Intrahepatic 2

Diseases in the Intrahepatic Cholestasis family:

Cholestasis, Progressive Familial Intrahepatic 2 Cholestasis, Benign Recurrent Intrahepatic, 2
Cholestasis, Progressive Familial Intrahepatic 3 Cholestasis, Progressive Familial Intrahepatic 4
Cholestasis, Progressive Familial Intrahepatic, 5 Cholestasis, Progressive Familial Intrahepatic 1
Cholestasis, Benign Recurrent Intrahepatic Abcb11-Related Intrahepatic Cholestasis
Atp8b1-Related Intrahepatic Cholestasis Myo5b-Related Progressive Familial Intrahepatic Cholestasis

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

(show all 20)
id Related Disease Score Top Affiliating Genes
1 cholestasis, progressive familial intrahepatic 1 10.8
2 cholestasis 10.5
3 intrahepatic cholestasis 10.5
4 pancreatitis 10.1
5 dermatomyositis 9.9 ABCB4 NR1H4
6 acute cholangitis 9.9 ABCB11 ABCB4
7 patent foramen ovale 9.9 ABCB11 NR1H4
8 prostate cancer, progression and metastasis of 9.9 ABCB4 NR1H4
9 cholestasis, intrahepatic, of pregnancy, 1 9.7 ABCB11 ATP8B1
10 isthmus cancer 9.6 ABCB11 ABCB4
11 alport syndrome and thin basement membrane nephropathy 9.4 ABCB11 ATP8B1 NR1H4
12 cholestasis, intrahepatic, of pregnancy, 3 9.3 ABCB11 ABCB4 ATP8B1
13 bardet-biedl syndrome 6 9.2 ABCB11 ABCB4 ATP8B1
14 orbital cancer 8.9 ABCB11 ABCB4 ATP8B1 NR1H4
15 hemorrhoid 8.9 ABCB11 ABCB4 ATP8B1 NR1H4
16 lymphoblastic lymphoma 8.8 ABCB11 ABCB4 ATP8B1 NR1H4
17 cholestasis, benign recurrent intrahepatic 8.4 ABCB11 ABCB4 ATP8B1 MYO5B NR1H4
18 chronic rheumatic pericarditis 8.3 ABCB11 ABCB4 ATP8B1 NR1H4 TJP2
19 eclampsia 8.3 ABCB11 ABCB4 ATP8B1 NR1H4 TJP2
20 cholestasis, benign recurrent intrahepatic, 2 7.8 ABCB11 ABCB4 ATP8B1 MYO5B NR1H4 TJP2

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:

54

Growth- Height:
short stature

Abdomen- Gastroin testinal:
diarrhea
malabsorption of fat and fat-soluble vitamins

Abdomen- Spleen:
splenomegaly

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

Growth- Other:
failure to thrive
growth retardation

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

Neoplasia:
increased risk of hepatocellular carcinoma


Clinical features from OMIM:

601847

Human phenotypes related to Cholestasis, Progressive Familial Intrahepatic 2:

32 (show all 13)
id Description HPO Frequency HPO Source Accession
1 short stature 32 HP:0004322
2 failure to thrive 32 HP:0001508
3 diarrhea 32 HP:0002014
4 hepatomegaly 32 HP:0002240
5 splenomegaly 32 HP:0001744
6 cirrhosis 32 HP:0001394
7 hepatocellular carcinoma 32 HP:0001402
8 intrahepatic cholestasis 32 HP:0001406
9 pruritus 32 HP:0000989
10 conjugated hyperbilirubinemia 32 HP:0002908
11 fat malabsorption 32 HP:0002630
12 elevated alkaline phosphatase 32 HP:0003155
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
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Downregulation of NF-kappaB pathway after LMP1 stimulation GR00199-A-1 8.96 NR1H4 TJP2
2 Downregulation of NF-kappaB pathway after TNFalpha stimulation GR00199-A-2 8.62 NR1H4 TJP2

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

44
id Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.43 ABCB11 ABCB4 ATP8B1 MYO5B NR1H4 TJP2
2 liver/biliary system MP:0005370 8.92 ABCB11 ABCB4 ATP8B1 NR1H4

Drugs & Therapeutics for Cholestasis, Progressive Familial Intrahepatic 2

Drugs for Cholestasis, Progressive Familial Intrahepatic 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Bile Acids and Salts Phase 2
2 Liver Extracts Phase 2
3 Alpha 1-Antitrypsin
4 Protein C Inhibitor

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Open Label Study to Evaluate Efficacy and Long Term Safety of LUM001 in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic Cholestasis Active, not recruiting NCT02057718 Phase 2 LUM001
2 Second-line Therapy of Unresectable Cholangiocarcinoma by RADIOEMBOLIZATION Terminated NCT01383746 Phase 1, Phase 2
3 Evaluating the Genetic Causes and Progression of Cholestatic Liver Diseases (LOGIC) Recruiting NCT00571272

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:

id Genetic test Affiliating Genes
1 Progressive Familial Intrahepatic Cholestasis 2 29
2 Progressive Familial Intrahepatic Cholestasis, Type 2 24

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic 2

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

39
Liver, Spleen

Publications for Cholestasis, Progressive Familial Intrahepatic 2

Variations for Cholestasis, Progressive Familial Intrahepatic 2

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

71 (show all 12)
id 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 19)
id 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.890A> G (p.Glu297Gly) single nucleotide variant Pathogenic rs11568372 GRCh37 Chromosome 2, 169847329: 169847329
3 ABCB11 ABCB11, 1-BP DEL, 908G deletion Pathogenic
4 ABCB11 NM_003742.2(ABCB11): c.3767_3768insC (p.Val1257Glyfs) insertion Pathogenic rs387907317 GRCh37 Chromosome 2, 169780331: 169780331
5 ABCB11 NM_003742.2(ABCB11): c.150+3A> C single nucleotide variant Pathogenic rs387906354 GRCh37 Chromosome 2, 169870810: 169870810
6 ABCB11 ABCB11, 5-BP INS, GAGAT insertion Pathogenic
7 ABCB11 NM_003742.2(ABCB11): c.3169C> T (p.Arg1057Ter) single nucleotide variant Pathogenic rs72549397 GRCh37 Chromosome 2, 169788931: 169788931
8 ABCB11 NM_003742.2(ABCB11): c.2012-8T> G single nucleotide variant Pathogenic rs769910565 GRCh37 Chromosome 2, 169825008: 169825008
9 ABCB11 NM_003742.2(ABCB11): c.908+1G> A single nucleotide variant Pathogenic rs147649016 GRCh37 Chromosome 2, 169847310: 169847310
10 ABCB11 NM_003742.2(ABCB11): c.3692G> A (p.Arg1231Gln) single nucleotide variant Pathogenic rs758069019 GRCh37 Chromosome 2, 169781240: 169781240
11 ABCB11 NM_003742.2(ABCB11): c.1271delA (p.Asn424Metfs) deletion Pathogenic rs886043703 GRCh37 Chromosome 2, 169833124: 169833124
12 ABCB11 NM_003742.2(ABCB11): c.1069G> T (p.Gly357Ter) single nucleotide variant Pathogenic rs886043935 GRCh37 Chromosome 2, 169842634: 169842634
13 ABCB11 NM_003742.2(ABCB11): c.1445A> G (p.Asp482Gly) single nucleotide variant Pathogenic rs72549402 GRCh37 Chromosome 2, 169828550: 169828550
14 ABCB11 NM_003742.2(ABCB11): c.22C> T (p.Arg8Ter) single nucleotide variant Pathogenic rs886043986 GRCh37 Chromosome 2, 169874614: 169874614
15 ABCB11 NM_003742.2(ABCB11): c.3457C> T (p.Arg1153Cys) single nucleotide variant Pathogenic rs72549395 GRCh37 Chromosome 2, 169783827: 169783827
16 ABCB11 NC_000002.11: g.169830232_169830305del56 deletion Pathogenic GRCh37 Chromosome 2, 169830232: 169830305
17 ABCB11 NM_003742.2(ABCB11): c.1460G> A (p.Arg487His) single nucleotide variant Likely pathogenic rs188824058 GRCh37 Chromosome 2, 169828535: 169828535
18 ABCB11 NM_003742.2(ABCB11): c.2296G> A (p.Gly766Arg) single nucleotide variant Likely pathogenic rs763782349 GRCh37 Chromosome 2, 169814521: 169814521
19 ABCB11 NM_003742.2(ABCB11): c.2380C> T (p.Gln794Ter) single nucleotide variant Pathogenic rs1060499579 GRCh37 Chromosome 2, 169801435: 169801435

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:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
11.42 ABCB11 ABCB4
2 11.18 ABCB11 ABCB4 NR1H4
3 10.68 ABCB11 ABCB4 NR1H4
4 10.49 ABCB11 NR1H4
5 10.08 ABCB11 ABCB4 NR1H4

GO Terms for Cholestasis, Progressive Familial Intrahepatic 2

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

id Name GO ID Score Top Affiliating Genes
1 apical part of cell GO:0045177 9.16 ABCB11 ABCB4
2 brush border membrane GO:0031526 8.96 ABCB4 ATP8B1
3 intercellular canaliculus GO:0046581 8.62 ABCB11 ABCB4

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

id Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.73 ABCB11 ABCB4 ATP8B1 MYO5B
2 lipid transport GO:0006869 9.4 ABCB4 ATP8B1
3 response to organic substance GO:0010033 9.37 ABCB4 TJP2
4 phospholipid translocation GO:0045332 9.32 ABCB4 ATP8B1
5 drug transmembrane transport GO:0006855 9.26 ABCB4 ATP8B1
6 intestinal absorption GO:0050892 9.16 ABCB4 TJP2
7 bile acid metabolic process GO:0008206 8.96 ATP8B1 NR1H4
8 bile acid and bile salt transport GO:0015721 8.8 ABCB11 ATP8B1 NR1H4

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

id Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.26 ABCB11 ABCB4 ATP8B1 MYO5B
2 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
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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