MCID: CHL081
MIFTS: 43

Cholestasis, Progressive Familial Intrahepatic 2 malady

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

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic 2

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Sources:
12diseasecard, 24GeneTests, 26GTR, 30ICD10 via Orphanet, 36MedGen, 38MeSH, 39MESH via Orphanet, 47NIH Rare Diseases, 49Novoseek, 51OMIM, 53Orphanet, 63The Human Phenotype Ontology, 67UMLS, 68UMLS via Orphanet, 69UniProtKB/Swiss-Prot
See all MalaCards sources

Aliases & Descriptions for Cholestasis, Progressive Familial Intrahepatic 2:

Name: Cholestasis, Progressive Familial Intrahepatic 2 51 12
Pfic2 47 24 53 69 49
Cholestasis, Progressive Familial Intrahepatic, 2 51 69 67
Progressive Familial Intrahepatic Cholestasis, Type 2 24 26
 
Progressive Familial Intrahepatic Cholestasis Type 2 47 53
Severe Abcb11 Deficiency 47
Bsep Deficiency 53
Pfic-2 24

Characteristics:

Orphanet epidemiological data:

53
pfic2:
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal

HPO:

63
cholestasis, progressive familial intrahepatic 2:
Inheritance: autosomal recessive inheritance
Onset and clinical course: infantile onset
Mortality/Aging: death in childhood

Classifications:



External Ids:

OMIM51 601847
Orphanet53 ORPHA79304
UMLS via Orphanet68 C1866138
ICD10 via Orphanet30 K76.8
MESH via Orphanet39 C535934
MeSH38 D002780

Summaries for Cholestasis, Progressive Familial Intrahepatic 2

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NIH Rare Diseases:47 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 pruritus, intermittent jaundice and cirrhosis. An important gene associated with Cholestasis, Progressive Familial Intrahepatic 2 is ABCB11 (ATP Binding Cassette Subfamily B Member 11), and among its related pathways are Hepatic ABC Transporters and Bile secretion. Affiliated tissues include liver and spleen, and related mouse phenotypes are growth/size/body region and liver/biliary system.

UniProtKB/Swiss-Prot:69 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:51 601847

Related Diseases for Cholestasis, Progressive Familial Intrahepatic 2

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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 1 Cholestasis, Benign Recurrent Intrahepatic
Abcb11-Related Intrahepatic Cholestasis Atp8b1-Related Intrahepatic Cholestasis
Cholestasis, Progressive Familial Intrahepatic 5

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

(show all 19)
idRelated DiseaseScoreTop Affiliating Genes
1cholestasis, progressive familial intrahepatic 111.0
2cholestasis10.5
3intrahepatic cholestasis10.5
4pancreatitis10.1
5paranasal sinus sarcoma9.9ABCB11, ABCB4
6ascending cholangitis9.9ABCB11, ABCB4
7lipid storage disease9.8ABCB11, ABCB4
8lrp5-related autosomal dominant osteopetrosis9.8ABCB11, ATP8B1
9adult-onset leukoencephalopathy with axonal spheroids and pigmented glia9.7ABCB11, ATP8B1
10perianal skin paget's disease9.7ABCB11, ABCB4
11amyotrophic lateral sclerosis 39.7ABCB11, ATP8B1
12dyserythropoietic anemia, congenital, type ii9.6ABCB4, ATP8B1
13prostate cancer, progression and metastasis of9.5ABCB11, ABCB4
14cholestasis, intrahepatic, of pregnancy, 19.3ABCB11, ABCB4, ATP8B1
15intraorbital meningioma9.3ABCB11, ABCB4, ATP8B1
16perianal hematoma9.3ABCB11, ABCB4, ATP8B1
17lymphoblastic lymphoma9.3ABCB11, ABCB4, ATP8B1
18giant cell reparative granuloma8.8ABCB11, ABCB4, ATP8B1, TJP2
19female infertility of uterine origin8.8ABCB11, ABCB4, ATP8B1, TJP2

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



Diseases related to cholestasis, progressive familial intrahepatic 2

Symptoms for Cholestasis, Progressive Familial Intrahepatic 2

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Symptoms by clinical synopsis from OMIM:

601847

Clinical features from OMIM:

601847

Human phenotypes related to Cholestasis, Progressive Familial Intrahepatic 2:

 63 (show all 13)
id Description HPO Frequency HPO Source Accession
1 pruritus63 HP:0000989
2 intermittent jaundice63 HP:0001046
3 cirrhosis63 HP:0001394
4 hepatocellular carcinoma63 HP:0001402
5 intrahepatic cholestasis63 HP:0001406
6 failure to thrive63 HP:0001508
7 splenomegaly63 HP:0001744
8 diarrhea63 HP:0002014
9 hepatomegaly63 HP:0002240
10 fat malabsorption63 HP:0002630
11 conjugated hyperbilirubinemia63 HP:0002908
12 elevated alkaline phosphatase63 HP:0003155
13 short stature63 HP:0004322

UMLS symptoms related to Cholestasis, Progressive Familial Intrahepatic 2:


diarrhea, hepatomegaly, pruritus

Drugs & Therapeutics for Cholestasis, Progressive Familial Intrahepatic 2

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

(show all 10)
idNameStatusPhaseClinical TrialsCas NumberPubChem Id
1Bile Acids and SaltsPhase 2102
2Liver ExtractsPhase 23868
3Hypolipidemic AgentsPhase 12721
4Lipid Regulating AgentsPhase 12702
5Cholestyramine ResinPhase 116
6AntimetabolitesPhase 111774
7Anticholesteremic AgentsPhase 11983
8ColaNutraceuticalPhase 11881
9Protein C Inhibitor97
10Alpha 1-Antitrypsin99

Interventional clinical trials:

idNameStatusNCT IDPhase
1Open Label Study to Evaluate Efficacy and Long Term Safety of LUM001 in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic CholestasisActive, not recruitingNCT02057718Phase 2
2Second-line Therapy of Unresectable Cholangiocarcinoma by RADIOEMBOLIZATIONTerminatedNCT01383746Phase 1, Phase 2
3A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384CompletedNCT02963077Phase 1
4Sulfation of Bile Acids as a Biomarker for Hepatobiliary DiseasesUnknown statusNCT01200082
5Evaluating the Genetic Causes and Progression of Cholestatic Liver Diseases (LOGIC)RecruitingNCT00571272

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Genetic Tests for Cholestasis, Progressive Familial Intrahepatic 2

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Genetic tests related to Cholestasis, Progressive Familial Intrahepatic 2:

id Genetic test Affiliating Genes
1 Progressive Familial Intrahepatic Cholestasis 226
2 Progressive Familial Intrahepatic Cholestasis, Type 224

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic 2

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

35
Liver, Spleen

Animal Models for Cholestasis, Progressive Familial Intrahepatic 2 or affiliated genes

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

40
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053788.7ABCB11, ABCB4, ATP8B1, TJP2
2MP:00053708.6ABCB11, ABCB4, ATP8B1

Publications for Cholestasis, Progressive Familial Intrahepatic 2

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Variations for Cholestasis, Progressive Familial Intrahepatic 2

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

69 (show all 12)
id Symbol AA change Variation ID SNP ID
1ABCB11p.Glu297GlyVAR_010271rs11568372
2ABCB11p.Val284LeuVAR_013332
3ABCB11p.Lys461GluVAR_013334
4ABCB11p.Asp482GlyVAR_013335rs72549402
5ABCB11p.Gly982ArgVAR_013336rs72549399
6ABCB11p.Gly1004AspVAR_013337
7ABCB11p.Arg1153CysVAR_013338rs72549395
8ABCB11p.Arg1268GlnVAR_013339rs72549394
9ABCB11p.Gly238ValVAR_030388rs72551306
10ABCB11p.Cys336SerVAR_030390rs72551305
11ABCB11p.Tyr472CysVAR_073968rs369860506
12ABCB11p.Asp1131ValVAR_073971

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

5 (show all 18)
id Gene Variation Type Significance SNP ID Assembly Location
1ABCB11NM_003742.2(ABCB11): c.2012-8T> GSNVPathogenicrs769910565GRCh37Chr 2, 169825008: 169825008
2ABCB11NM_003742.2(ABCB11): c.908+1G> ASNVPathogenicrs147649016GRCh37Chr 2, 169847310: 169847310
3ABCB11NM_003742.2(ABCB11): c.3692G> A (p.Arg1231Gln)SNVPathogenicrs758069019GRCh37Chr 2, 169781240: 169781240
4ABCB11NM_003742.2(ABCB11): c.1271delA (p.Asn424Metfs)deletionPathogenicrs886043703GRCh37Chr 2, 169833124: 169833124
5ABCB11NM_003742.2(ABCB11): c.1069G> T (p.Gly357Ter)SNVPathogenicrs886043935GRCh37Chr 2, 169842634: 169842634
6ABCB11NM_003742.2(ABCB11): c.1445A> G (p.Asp482Gly)SNVPathogenicrs72549402GRCh37Chr 2, 169828550: 169828550
7ABCB11NM_003742.2(ABCB11): c.22C> T (p.Arg8Ter)SNVPathogenicrs886043986GRCh37Chr 2, 169874614: 169874614
8ABCB11NM_003742.2(ABCB11): c.3457C> T (p.Arg1153Cys)SNVPathogenicrs72549395GRCh37Chr 2, 169783827: 169783827
9ABCB11NC_000002.11: g.169830232_169830305del56deletionPathogenicGRCh37Chr 2, 169830232: 169830305
10ABCB11NM_003742.2(ABCB11): c.1460G> A (p.Arg487His)SNVLikely pathogenicrs188824058GRCh37Chr 2, 169828535: 169828535
11ABCB11NM_003742.2(ABCB11): c.2296G> A (p.Gly766Arg)SNVLikely pathogenicrs763782349GRCh37Chr 2, 169814521: 169814521
12ABCB11NM_003742.2(ABCB11): c.1723C> T (p.Arg575Ter)SNVPathogenicrs72549401GRCh37Chr 2, 169826641: 169826641
13ABCB11NM_003742.2(ABCB11): c.890A> G (p.Glu297Gly)SNVPathogenicrs11568372GRCh37Chr 2, 169847329: 169847329
14ABCB11ABCB11, 1-BP DEL, 908GdeletionPathogenicChr na, -1: -1
15ABCB11NM_003742.2(ABCB11): c.3767dupC (p.Val1257Glyfs)duplicationPathogenicrs387907317GRCh37Chr 2, 169780331: 169780331
16ABCB11NM_003742.2(ABCB11): c.150+3A> CSNVPathogenicrs387906354GRCh37Chr 2, 169870810: 169870810
17ABCB11ABCB11, 5-BP INS, GAGATinsertionPathogenicChr na, -1: -1
18ABCB11NM_003742.2(ABCB11): c.3169C> T (p.Arg1057Ter)SNVPathogenicrs72549397GRCh37Chr 2, 169788931: 169788931

Expression for genes affiliated with Cholestasis, Progressive Familial Intrahepatic 2

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

Pathways for genes affiliated with Cholestasis, Progressive Familial Intrahepatic 2

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

idSuper pathwaysScoreTop Affiliating Genes
1
Show member pathways
9.4ABCB11, ABCB4
29.4ABCB11, ABCB4
39.4ABCB11, ABCB4

GO Terms for genes affiliated with Cholestasis, Progressive Familial Intrahepatic 2

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

idNameGO IDScoreTop Affiliating Genes
1intercellular canaliculusGO:00465819.7ABCB11, ABCB4
2apical plasma membraneGO:00163249.4ABCB4, ATP8B1
3integral component of plasma membraneGO:00058878.6ABCB11, ABCB4, ATP8B1
4plasma membraneGO:00058867.7ABCB11, ABCB4, ATP8B1, TJP2

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

idNameGO IDScoreTop Affiliating Genes
1drug transmembrane transportGO:00068559.7ABCB4, ATP8B1
2phospholipid translocationGO:00453329.7ABCB4, ATP8B1
3bile acid and bile salt transportGO:00157219.7ABCB11, ATP8B1
4transportGO:00068109.4ABCB11, ABCB4

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

idNameGO IDScoreTop Affiliating Genes
1ATP bindingGO:00055248.6ABCB11, ABCB4, ATP8B1

Sources for Cholestasis, Progressive Familial Intrahepatic 2

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
26GTR
27HGMD
28HMDB
29ICD10
30ICD10 via Orphanet
31ICD9CM
32IUPHAR
33KEGG
36MedGen
38MeSH
39MESH via Orphanet
40MGI
43NCI
44NCIt
45NDF-RT
48NINDS
49Novoseek
51OMIM
52OMIM via Orphanet
56PubMed
57QIAGEN
62SNOMED-CT via Orphanet
66Tumor Gene Family of Databases
67UMLS
68UMLS via Orphanet