PFIC4
MCID: CHL143
MIFTS: 36

Cholestasis, Progressive Familial Intrahepatic, 4 (PFIC4)

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

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic, 4

MalaCards integrated aliases for Cholestasis, Progressive Familial Intrahepatic, 4:

Name: Cholestasis, Progressive Familial Intrahepatic, 4 58 76
Progressive Familial Intrahepatic Cholestasis 4 12 54 30 6 15
Pfic4 58 12 54 60 76
Cholestasis, Progressive Familial Intrahepatic 4 58 54 74
Tjp2 Deficit 12 60
3-Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase Deficiency 54
Cholestasis, Intrahepatic, Familial, Progressive, Type 4 41
Progressive Familial Intrahepatic Cholestasis Type 4 60
Bile Acid Synthesis Defect, Congenital, 1 74

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in childhood
most patients require liver transplant in childhood


HPO:

33
cholestasis, progressive familial intrahepatic, 4:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0070224
OMIM 58 615878
MeSH 45 D002780
Orphanet 60 ORPHA480483
MedGen 43 C2931067

Summaries for Cholestasis, Progressive Familial Intrahepatic, 4

UniProtKB/Swiss-Prot : 76 Cholestasis, progressive familial intrahepatic, 4: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood.

MalaCards based summary : Cholestasis, Progressive Familial Intrahepatic, 4, also known as progressive familial intrahepatic cholestasis 4, is related to congenital bile acid synthesis defect and bile acid synthesis defect, congenital, 1, and has symptoms including diarrhea and icterus. An important gene associated with Cholestasis, Progressive Familial Intrahepatic, 4 is TJP2 (Tight Junction Protein 2), and among its related pathways/superpathways are Hepatic ABC Transporters and Bile secretion. Affiliated tissues include liver, and related phenotypes are portal hypertension and hepatic failure

Disease Ontology : 12 A progressive familial intrahepatic cholestasis characterized by autosomal recessive inheritance that has material basis in mutation in the TJP2 gene on chromosome 9q21.

Description from OMIM: 615878

Related Diseases for Cholestasis, Progressive Familial Intrahepatic, 4

Diseases in the Progressive 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 Myo5b-Related Progressive Familial Intrahepatic Cholestasis

Diseases related to Cholestasis, Progressive Familial Intrahepatic, 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)
# Related Disease Score Top Affiliating Genes
1 congenital bile acid synthesis defect 11.9
2 bile acid synthesis defect, congenital, 1 11.5
3 atp8b1 deficiency 9.9 ABCB11 ATP8B1
4 cholestasis, benign recurrent intrahepatic, 2 9.8 ABCB11 ATP8B1
5 cholestasis, benign recurrent intrahepatic, 1 9.8 ABCB11 ATP8B1
6 sclerosing cholangitis 9.6 ABCB11 ABCB4
7 cholangitis 9.5 ABCB11 ABCB4
8 cholestasis, progressive familial intrahepatic, 2 9.5 ABCB11 ABCB4 ATP8B1
9 cholestasis, progressive familial intrahepatic, 3 9.5 ABCB11 ABCB4 ATP8B1
10 alagille syndrome 1 9.5 ABCB11 ABCB4 ATP8B1
11 cholestasis, progressive familial intrahepatic, 1 9.5 ABCB11 ABCB4 ATP8B1
12 bile duct disease 9.4 ABCB11 ABCB4 ATP8B1
13 biliary tract disease 9.4 ABCB11 ABCB4 ATP8B1
14 intrahepatic cholestasis of pregnancy 9.4 ABCB11 ABCB4 ATP8B1
15 liver disease 9.4 ABCB11 ABCB4 ATP8B1
16 cholestasis 9.2 ABCB11 ABCB4 ATP8B1 TJP2
17 progressive familial intrahepatic cholestasis 9.2 ABCB11 ABCB4 ATP8B1 TJP2

Graphical network of the top 20 diseases related to Cholestasis, Progressive Familial Intrahepatic, 4:



Diseases related to Cholestasis, Progressive Familial Intrahepatic, 4

Symptoms & Phenotypes for Cholestasis, Progressive Familial Intrahepatic, 4

Human phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 4:

33
# Description HPO Frequency HPO Source Accession
1 portal hypertension 33 HP:0001409
2 hepatic failure 33 HP:0001399
3 intrahepatic cholestasis 33 HP:0001406
4 hepatocellular carcinoma 33 HP:0001402

Symptoms via clinical synopsis from OMIM:

58
Abdomen Liver:
portal hypertension
intrahepatic cholestasis
liver failure
elongated tight junctions between adjacent hepatocytes and biliary canaliculi seen on biopsy

Laboratory Abnormalities:
normal or mildly increased serum gamma-glutamyltransferase (ggt)

Neoplasia:
hepatocellular carcinoma, childhood onset (reported in 2 patients)

Clinical features from OMIM:

615878

UMLS symptoms related to Cholestasis, Progressive Familial Intrahepatic, 4:


diarrhea, icterus

GenomeRNAi Phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 4 according to GeneCards Suite gene sharing:

27
# 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, 4:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.26 ABCB11 ABCB4 ATP8B1 TJP2
2 liver/biliary system MP:0005370 8.8 ABCB11 ABCB4 ATP8B1

Drugs & Therapeutics for Cholestasis, Progressive Familial Intrahepatic, 4

Search Clinical Trials , NIH Clinical Center for Cholestasis, Progressive Familial Intrahepatic, 4

Genetic Tests for Cholestasis, Progressive Familial Intrahepatic, 4

Genetic tests related to Cholestasis, Progressive Familial Intrahepatic, 4:

# Genetic test Affiliating Genes
1 Progressive Familial Intrahepatic Cholestasis 4 30 TJP2

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic, 4

MalaCards organs/tissues related to Cholestasis, Progressive Familial Intrahepatic, 4:

42
Liver

Publications for Cholestasis, Progressive Familial Intrahepatic, 4

Articles related to Cholestasis, Progressive Familial Intrahepatic, 4:

# Title Authors Year
1
Hepatocellular carcinoma associated with tight-junction protein 2 deficiency. ( 25921221 )
2015
2
Mutations in TJP2 cause progressive cholestatic liver disease. ( 24614073 )
2014

Variations for Cholestasis, Progressive Familial Intrahepatic, 4

ClinVar genetic disease variations for Cholestasis, Progressive Familial Intrahepatic, 4:

6 (show all 30)
# Gene Variation Type Significance SNP ID Assembly Location
1 TJP2 NM_004817.3(TJP2): c.766_769delGCCT (p.Ala256Thrfs) deletion Pathogenic rs587777518 GRCh37 Chromosome 9, 71836226: 71836229
2 TJP2 NM_004817.3(TJP2): c.766_769delGCCT (p.Ala256Thrfs) deletion Pathogenic rs587777518 GRCh38 Chromosome 9, 69221310: 69221313
3 TJP2 NM_004817.3(TJP2): c.885delC (p.Ser296Alafs) deletion Pathogenic rs587777519 GRCh37 Chromosome 9, 71836345: 71836345
4 TJP2 NM_004817.3(TJP2): c.885delC (p.Ser296Alafs) deletion Pathogenic rs587777519 GRCh38 Chromosome 9, 69221429: 69221429
5 TJP2 NM_004817.3(TJP2): c.1361delC (p.Ala454Glyfs) deletion Pathogenic rs587777520 GRCh37 Chromosome 9, 71842938: 71842938
6 TJP2 NM_004817.3(TJP2): c.1361delC (p.Ala454Glyfs) deletion Pathogenic rs587777520 GRCh38 Chromosome 9, 69228022: 69228022
7 TJP2 NM_004817.4(TJP2): c.1992-2A> G single nucleotide variant Pathogenic rs587777521 GRCh37 Chromosome 9, 71851863: 71851863
8 TJP2 NM_004817.4(TJP2): c.1992-2A> G single nucleotide variant Pathogenic rs587777521 GRCh38 Chromosome 9, 69236947: 69236947
9 TJP2 NM_004817.4(TJP2): c.1258C> T (p.Arg420Cys) single nucleotide variant Uncertain significance rs199761505 GRCh38 Chromosome 9, 69227812: 69227812
10 TJP2 NM_004817.4(TJP2): c.1258C> T (p.Arg420Cys) single nucleotide variant Uncertain significance rs199761505 GRCh37 Chromosome 9, 71842728: 71842728
11 TJP2 NM_004817.3(TJP2): c.3408_3573del166 (p.Ser1136Argfs) deletion Pathogenic rs1554669525 GRCh37 Chromosome 9, 71869125: 71869290
12 TJP2 NM_004817.3(TJP2): c.3408_3573del166 (p.Ser1136Argfs) deletion Pathogenic rs1554669525 GRCh38 Chromosome 9, 69254209: 69254374
13 TJP2 NM_004817.4(TJP2): c.2668-1G> T single nucleotide variant Pathogenic rs864321695 GRCh37 Chromosome 9, 71862927: 71862927
14 TJP2 NM_004817.4(TJP2): c.2668-1G> T single nucleotide variant Pathogenic rs864321695 GRCh38 Chromosome 9, 69248011: 69248011
15 TJP2 NM_004817.4(TJP2): c.2438dup (p.Asn814Glnfs) duplication Pathogenic rs776869985 GRCh37 Chromosome 9, 71854935: 71854935
16 TJP2 NM_004817.4(TJP2): c.2438dup (p.Asn814Glnfs) duplication Pathogenic rs776869985 GRCh38 Chromosome 9, 69240019: 69240019
17 TJP2 NM_004817.3(TJP2): c.817delG (p.Ala273Profs) deletion Pathogenic rs864321697 GRCh37 Chromosome 9, 71836277: 71836277
18 TJP2 NM_004817.3(TJP2): c.817delG (p.Ala273Profs) deletion Pathogenic rs864321697 GRCh38 Chromosome 9, 69221361: 69221361
19 TJP2 NM_004817.3(TJP2): c.498dupG (p.Arg167Alafs) duplication Pathogenic rs781334233 GRCh37 Chromosome 9, 71835958: 71835958
20 TJP2 NM_004817.3(TJP2): c.498dupG (p.Arg167Alafs) duplication Pathogenic rs781334233 GRCh38 Chromosome 9, 69221042: 69221042
21 TJP2 NM_004817.3(TJP2): c.1243delT (p.Ser415Leufs) deletion Pathogenic rs1057518679 GRCh37 Chromosome 9, 71842713: 71842713
22 TJP2 NM_004817.3(TJP2): c.1243delT (p.Ser415Leufs) deletion Pathogenic rs1057518679 GRCh38 Chromosome 9, 69227797: 69227797
23 TJP2 NG_016342.1: g.(102053_104579)_(123841_130382)dup duplication Pathogenic GRCh38 Chromosome 9, 69218360: 69246689
24 TJP2 NG_016342.1: g.(102053_104579)_(123841_130382)dup duplication Pathogenic GRCh37 Chromosome 9, 71833276: 71861605
25 TJP2 NM_004817.4(TJP2): c.1210G> A (p.Asp404Asn) single nucleotide variant Likely pathogenic rs1060499649 GRCh38 Chromosome 9, 69226175: 69226175
26 TJP2 NM_004817.4(TJP2): c.1210G> A (p.Asp404Asn) single nucleotide variant Likely pathogenic rs1060499649 GRCh37 Chromosome 9, 71841091: 71841091
27 TJP2 NM_004817.3(TJP2): c.813_814delCG (p.Ala273Profs) deletion Pathogenic rs1554660803 GRCh38 Chromosome 9, 69221357: 69221358
28 TJP2 NM_004817.3(TJP2): c.813_814delCG (p.Ala273Profs) deletion Pathogenic rs1554660803 GRCh37 Chromosome 9, 71836271: 71836272
29 TJP2 NM_004817.4(TJP2): c.1056+2T> C single nucleotide variant Likely pathogenic rs1278244243 GRCh37 Chromosome 9, 71840325: 71840325
30 TJP2 NM_004817.4(TJP2): c.1056+2T> C single nucleotide variant Likely pathogenic rs1278244243 GRCh38 Chromosome 9, 69225409: 69225409

Expression for Cholestasis, Progressive Familial Intrahepatic, 4

Search GEO for disease gene expression data for Cholestasis, Progressive Familial Intrahepatic, 4.

Pathways for Cholestasis, Progressive Familial Intrahepatic, 4

Pathways related to Cholestasis, Progressive Familial Intrahepatic, 4 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, 4

Cellular components related to Cholestasis, Progressive Familial Intrahepatic, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 apical plasma membrane GO:0016324 9.16 ABCB4 ATP8B1
2 integral component of plasma membrane GO:0005887 9.13 ABCB11 ABCB4 ATP8B1
3 intercellular canaliculus GO:0046581 8.62 ABCB11 ABCB4

Biological processes related to Cholestasis, Progressive Familial Intrahepatic, 4 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 phospholipid translocation GO:0045332 8.96 ABCB4 ATP8B1
4 drug transmembrane transport GO:0006855 8.32 ATP8B1

Molecular functions related to Cholestasis, Progressive Familial Intrahepatic, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.33 ABCB11 ABCB4 ATP8B1
2 ATPase activity GO:0016887 8.96 ABCB11 ABCB4
3 ATPase activity, coupled to transmembrane movement of substances GO:0042626 8.62 ABCB11 ABCB4

Sources for Cholestasis, Progressive Familial Intrahepatic, 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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