PFIC4
MCID: CHL143
MIFTS: 35

Cholestasis, Progressive Familial Intrahepatic, 4 (PFIC4)

Categories: Cancer diseases, Endocrine 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 57 75
Progressive Familial Intrahepatic Cholestasis 4 12 53 29 6 15
Pfic4 57 12 53 59 75
Cholestasis, Progressive Familial Intrahepatic 4 57 53 73
Tjp2 Deficit 12 59
3-Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase Deficiency 53
Cholestasis, Intrahepatic, Familial, Progressive, Type 4 40
Progressive Familial Intrahepatic Cholestasis Type 4 59
Bile Acid Synthesis Defect, Congenital, 1 73

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
cholestasis, progressive familial intrahepatic, 4:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 615878
Disease Ontology 12 DOID:0070224
Orphanet 59 ORPHA480483
MedGen 42 C2931067
MeSH 44 D002780

Summaries for Cholestasis, Progressive Familial Intrahepatic, 4

UniProtKB/Swiss-Prot : 75 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 11.8
2 bile acid synthesis defect, congenital, 1 11.5
3 atp8b1 deficiency 9.9 ABCB11 ATP8B1
4 cholestasis, benign recurrent intrahepatic, 2 9.9 ABCB11 ATP8B1
5 cholestasis, benign recurrent intrahepatic, 1 9.9 ABCB11 ATP8B1
6 sclerosing cholangitis 9.8 ABCB11 ABCB4
7 cholangitis 9.7 ABCB11 ABCB4
8 cholestasis, progressive familial intrahepatic, 2 9.7 ABCB11 ABCB4 ATP8B1
9 cholestasis, progressive familial intrahepatic, 3 9.7 ABCB11 ABCB4 ATP8B1
10 alagille syndrome 1 9.7 ABCB11 ABCB4 ATP8B1
11 cholestasis, progressive familial intrahepatic, 1 9.6 ABCB11 ABCB4 ATP8B1
12 bile duct disease 9.6 ABCB11 ABCB4 ATP8B1
13 biliary tract disease 9.6 ABCB11 ABCB4 ATP8B1
14 intrahepatic cholestasis of pregnancy 9.6 ABCB11 ABCB4 ATP8B1
15 liver disease 9.6 ABCB11 ABCB4 ATP8B1
16 cholestasis 9.5 ABCB11 ABCB4 ATP8B1 TJP2
17 progressive familial intrahepatic cholestasis 9.5 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

Symptoms via clinical synopsis from OMIM:

57
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

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

32
# Description HPO Frequency HPO Source Accession
1 portal hypertension 32 HP:0001409
2 hepatic failure 32 HP:0001399
3 intrahepatic cholestasis 32 HP:0001406
4 hepatocellular carcinoma 32 HP:0001402

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:

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, 4:

46
# 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 29 TJP2

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic, 4

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

41
Liver

Publications for Cholestasis, Progressive Familial Intrahepatic, 4

Variations for Cholestasis, Progressive Familial Intrahepatic, 4

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

6 (show all 31)
# 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_004817.3(TJP2): c.1992-2A> G single nucleotide variant Pathogenic rs587777521 GRCh37 Chromosome 9, 71851863: 71851863
8 TJP2 NM_004817.3(TJP2): c.1992-2A> G single nucleotide variant Pathogenic rs587777521 GRCh38 Chromosome 9, 69236947: 69236947
9 TJP2 NM_004817.3(TJP2): c.3408_3573del166 (p.Ser1136Argfs) deletion Pathogenic GRCh37 Chromosome 9, 71869125: 71869290
10 TJP2 NM_004817.3(TJP2): c.3408_3573del166 (p.Ser1136Argfs) deletion Pathogenic GRCh38 Chromosome 9, 69254209: 69254374
11 TJP2 NM_004817.3(TJP2): c.2668-1G> T single nucleotide variant Pathogenic rs864321695 GRCh37 Chromosome 9, 71862927: 71862927
12 TJP2 NM_004817.3(TJP2): c.2668-1G> T single nucleotide variant Pathogenic rs864321695 GRCh38 Chromosome 9, 69248011: 69248011
13 TJP2 NM_004817.3(TJP2): c.2438dupT (p.Asn814Glnfs) duplication Pathogenic rs864321696 GRCh37 Chromosome 9, 71854935: 71854935
14 TJP2 NM_004817.3(TJP2): c.2438dupT (p.Asn814Glnfs) duplication Pathogenic rs864321696 GRCh38 Chromosome 9, 69240019: 69240019
15 TJP2 NM_004817.3(TJP2): c.817delG (p.Ala273Profs) deletion Pathogenic rs864321697 GRCh37 Chromosome 9, 71836277: 71836277
16 TJP2 NM_004817.3(TJP2): c.817delG (p.Ala273Profs) deletion Pathogenic rs864321697 GRCh38 Chromosome 9, 69221361: 69221361
17 TJP2 NM_004817.3(TJP2): c.1697T> A (p.Leu566Ter) single nucleotide variant Pathogenic rs886042381 GRCh37 Chromosome 9, 71849380: 71849380
18 TJP2 NM_004817.3(TJP2): c.1697T> A (p.Leu566Ter) single nucleotide variant Pathogenic rs886042381 GRCh38 Chromosome 9, 69234464: 69234464
19 TJP2 NM_004817.3(TJP2): c.498dupG (p.Arg167Alafs) duplication Pathogenic rs886044313 GRCh37 Chromosome 9, 71835958: 71835958
20 TJP2 NM_004817.3(TJP2): c.498dupG (p.Arg167Alafs) duplication Pathogenic rs886044313 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_004817.3(TJP2): c.1210G> A (p.Asp404Asn) single nucleotide variant Likely pathogenic rs1060499649 GRCh38 Chromosome 9, 69226175: 69226175
26 TJP2 NM_004817.3(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 GRCh38 Chromosome 9, 69221357: 69221358
28 TJP2 NM_004817.3(TJP2): c.782delA (p.Tyr261Serfs) deletion Pathogenic rs771690686 GRCh38 Chromosome 9, 69221326: 69221326
29 TJP2 NM_004817.3(TJP2): c.782delA (p.Tyr261Serfs) deletion Pathogenic rs771690686 GRCh37 Chromosome 9, 71836242: 71836242
30 TJP2 NM_001170416.1(TJP2): c.108delC (p.Asn37Thrfs) deletion Pathogenic GRCh38 Chromosome 9, 69205269: 69205269
31 TJP2 NM_001170416.1(TJP2): c.108delC (p.Asn37Thrfs) deletion Pathogenic GRCh37 Chromosome 9, 71820185: 71820185

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 8.62 ABCB4 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 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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