PFIC2
MCID: CHL081
MIFTS: 45

Cholestasis, Progressive Familial Intrahepatic 2 (PFIC2) 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, 27GTR, 31ICD10 via Orphanet, 37MedGen, 39MeSH, 40MESH via Orphanet, 48NIH Rare Diseases, 50Novoseek, 52OMIM, 54Orphanet, 64The Human Phenotype Ontology, 68UMLS, 69UMLS via Orphanet, 70UniProtKB/Swiss-Prot
See all MalaCards sources

Aliases & Descriptions for Cholestasis, Progressive Familial Intrahepatic 2:

Name: Cholestasis, Progressive Familial Intrahepatic 2 52 12
Pfic2 48 24 54 70 50
Cholestasis, Progressive Familial Intrahepatic, 2 52 70 68
Progressive Familial Intrahepatic Cholestasis, Type 2 24 27
 
Progressive Familial Intrahepatic Cholestasis Type 2 48 54
Severe Abcb11 Deficiency 48
Bsep Deficiency 54
Pfic-2 24

Characteristics:

Orphanet epidemiological data:

54
pfic2:
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal

HPO:

64
cholestasis, progressive familial intrahepatic 2:
Inheritance: autosomal recessive inheritance
Onset and clinical course: infantile onset
Mortality/Aging: death in childhood

Classifications:



External Ids:

OMIM52 601847
Orphanet54 ORPHA79304
UMLS via Orphanet69 C1866138
ICD10 via Orphanet31 K76.8
MESH via Orphanet40 C535934
MeSH39 D002780

Summaries for Cholestasis, Progressive Familial Intrahepatic 2

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NIH Rare Diseases:48 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 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 are Hepatic ABC Transporters and Drug Induction of Bile Acid Pathway. Affiliated tissues include liver and spleen, and related mouse phenotypes are Downregulation of NF-kappaB pathway after LMP1 stimulation and Downregulation of NF-kappaB pathway after TNFalpha stimulation.

UniProtKB/Swiss-Prot:70 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:52 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 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)
idRelated DiseaseScoreTop Affiliating Genes
1cholestasis, progressive familial intrahepatic 111.0
2cholestasis10.5
3intrahepatic cholestasis10.5
4pancreatitis10.1
5acute cholangitis10.0ABCB11, ABCB4
6borderline leprosy9.9ABCB4, NR1H4
7pseudoarthrosis9.9ABCB4, NR1H4
8autosomal dominant tubulointerstitial kidney disease, muc1-related9.9ABCB11, ATP8B1, NR1H4
9dyserythropoietic anemia, congenital, type ii9.9ABCB4, ATP8B1
10bacterial meningitis9.8ABCB11, ABCB4
11marfan syndrome/loeys-dietz syndrome/familial thoracic aortic aneurysms and dissections9.8ABCB11, ABCB4, ATP8B1
12gallbladder disease 19.8ABCB11, ABCB4, ATP8B1
13lymphoid leukemia9.8ABCB11, ABCB4, ATP8B1
14amyotrophic lateral sclerosis 39.7ABCB11, ABCB4, ATP8B1, NR1H4
15gastrointestinal adenoma9.7ABCB11, ABCB4, ATP8B1, NR1H4
16heart aneurysm9.6ABCB11, ABCB4, ATP8B1, NR1H4
17eclampsia9.6ABCB11, ABCB4, ATP8B1, NR1H4
18chronic rheumatic pericarditis9.5ABCB11, ABCB4, ATP8B1, NR1H4, TJP2
19cholestasis, intrahepatic, of pregnancy, 19.3ABCB11, ABCB4, ATP8B1, MYO5B, NR1H4
20cholestasis, benign recurrent intrahepatic, 29.2ABCB11, ABCB4, ATP8B1, MYO5B, NR1H4, TJP2

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



Diseases related to cholestasis, progressive familial intrahepatic 2

Symptoms & Phenotypes 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:

 64 (show all 13)
id Description HPO Frequency HPO Source Accession
1 pruritus64 HP:0000989
2 intermittent jaundice64 HP:0001046
3 cirrhosis64 HP:0001394
4 hepatocellular carcinoma64 HP:0001402
5 intrahepatic cholestasis64 HP:0001406
6 failure to thrive64 HP:0001508
7 splenomegaly64 HP:0001744
8 diarrhea64 HP:0002014
9 hepatomegaly64 HP:0002240
10 fat malabsorption64 HP:0002630
11 conjugated hyperbilirubinemia64 HP:0002908
12 elevated alkaline phosphatase64 HP:0003155
13 short stature64 HP:0004322

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
idDescriptionGenomeRNAi Source AccessionScoreTop Affiliating Genes
1GR00199-A-110.2NR1H4, TJP2
2GR00199-A-210.2NR1H4, TJP2

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

41
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053708.1ABCB11, ABCB4, ATP8B1, NR1H4
2MP:00053787.8ABCB11, ABCB4, ATP8B1, MYO5B, NR1H4, TJP2

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 2106
2Liver ExtractsPhase 24067
3Hypolipidemic AgentsPhase 12785
4Lipid Regulating AgentsPhase 12766
5Cholestyramine ResinPhase 116
6AntimetabolitesPhase 112054
7Anticholesteremic AgentsPhase 12025
8ColaNutraceuticalPhase 11946
9Protein C Inhibitor98
10Alpha 1-Antitrypsin100

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

Search NIH Clinical Center for Cholestasis, Progressive Familial Intrahepatic 2

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 227
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:

36
Liver, Spleen

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:

70 (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 19)
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.2380C> T (p.Gln794Ter)SNVPathogenicrs1060499579GRCh37Chr 2, 169801435: 169801435
13ABCB11NM_ 003742.2(ABCB11): c.1723C> T (p.Arg575Ter)SNVPathogenicrs72549401GRCh37Chr 2, 169826641: 169826641
14ABCB11NM_ 003742.2(ABCB11): c.890A> G (p.Glu297Gly)SNVPathogenicrs11568372GRCh37Chr 2, 169847329: 169847329
15ABCB11ABCB11, 1-BP DEL, 908GdeletionPathogenic
16ABCB11NM_ 003742.2(ABCB11): c.3767dupC (p.Val1257Glyfs)duplicationPathogenicrs387907317GRCh37Chr 2, 169780331: 169780331
17ABCB11NM_ 003742.2(ABCB11): c.150+3A> CSNVPathogenicrs387906354GRCh37Chr 2, 169870810: 169870810
18ABCB11ABCB11, 5-BP INS, GAGATinsertionPathogenic
19ABCB11NM_ 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
9.5ABCB11, ABCB4
29.4ABCB11, NR1H4
38.9ABCB11, ABCB4, NR1H4
48.9ABCB11, ABCB4, NR1H4
58.9ABCB11, ABCB4, NR1H4

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
1apical part of cellGO:004517710.0ABCB11, ABCB4
2intercellular canaliculusGO:00465819.5ABCB11, ABCB4
3brush border membraneGO:00315269.3ABCB4, ATP8B1

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

(show all 8)
idNameGO IDScoreTop Affiliating Genes
1intestinal absorptionGO:005089210.2ABCB4, TJP2
2response to organic substanceGO:001003310.2ABCB4, TJP2
3drug transmembrane transportGO:00068559.9ABCB4, ATP8B1
4lipid transportGO:00068699.9ABCB4, ATP8B1
5phospholipid translocationGO:00453329.9ABCB4, ATP8B1
6bile acid metabolic processGO:00082069.8ATP8B1, NR1H4
7bile acid and bile salt transportGO:00157219.4ABCB11, ATP8B1, NR1H4
8transportGO:00068108.2ABCB11, ABCB4, ATP8B1, MYO5B

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

idNameGO IDScoreTop Affiliating Genes
1ATPase activity, coupled to transmembrane movement of substancesGO:00426269.5ABCB11, ABCB4
2ATP bindingGO:00055248.6ABCB11, ABCB4, ATP8B1, MYO5B

Sources for Cholestasis, Progressive Familial Intrahepatic 2

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
27GTR
28HGMD
29HMDB
30ICD10
31ICD10 via Orphanet
32ICD9CM
33IUPHAR
34KEGG
37MedGen
39MeSH
40MESH via Orphanet
41MGI
44NCI
45NCIt
46NDF-RT
49NINDS
50Novoseek
52OMIM
53OMIM via Orphanet
57PubMed
58QIAGEN
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
68UMLS
69UMLS via Orphanet