MCID: CHL083
MIFTS: 27

Cholestasis, Progressive Familial Intrahepatic 4

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

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic 4

MalaCards integrated aliases for Cholestasis, Progressive Familial Intrahepatic 4:

Name: Cholestasis, Progressive Familial Intrahepatic 4 54 50 24 69
Pfic4 50 24 56 71
Progressive Familial Intrahepatic Cholestasis 4 50 29
3-Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase Deficiency 50
Progressive Familial Intrahepatic Cholestasis Type 4 56
Cholestasis, Progressive Familial Intrahepatic, 4 71
Bile Acid Synthesis Defect, Congenital, 1 69
Tjp2 Deficit 56

Characteristics:

OMIM:

54
Miscellaneous:
most patients require liver transplant in childhood
onset in childhood
progressive disorder

Inheritance:
autosomal recessive


HPO:

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


Classifications:



External Ids:

OMIM 54 615878
Orphanet 56 ORPHA480483
MedGen 40 C2931067
MeSH 42 D002780

Summaries for Cholestasis, Progressive Familial Intrahepatic 4

UniProtKB/Swiss-Prot : 71 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 pfic4, is related to bile acid synthesis defect, congenital, 1 and congenital bile acid synthesis defect, and has symptoms including hepatic failure, portal hypertension and intrahepatic cholestasis. An important gene associated with Cholestasis, Progressive Familial Intrahepatic 4 is TJP2 (Tight Junction Protein 2). The drugs Anticholesteremic Agents and Antimetabolites have been mentioned in the context of this disorder. Affiliated tissues include liver.

Description from OMIM: 615878

Related Diseases for Cholestasis, Progressive Familial Intrahepatic 4

Symptoms & Phenotypes for Cholestasis, Progressive Familial Intrahepatic 4

Symptoms via clinical synopsis from OMIM:

54

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

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

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


Clinical features from OMIM:

615878

Human phenotypes related to Cholestasis, Progressive Familial Intrahepatic 4:

32
id Description HPO Frequency HPO Source Accession
1 hepatic failure 32 HP:0001399
2 portal hypertension 32 HP:0001409
3 intrahepatic cholestasis 32 HP:0001406

UMLS symptoms related to Cholestasis, Progressive Familial Intrahepatic 4:


diarrhea, icterus

Drugs & Therapeutics for Cholestasis, Progressive Familial Intrahepatic 4

Drugs for Cholestasis, Progressive Familial Intrahepatic 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 11)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anticholesteremic Agents Phase 1
2 Antimetabolites Phase 1
3 Cholestyramine Resin Phase 1
4 Hypolipidemic Agents Phase 1
5 Lipid Regulating Agents Phase 1
6 Cola Nutraceutical Phase 1
7 Estrogens
8 Alpha 1-Antitrypsin
9 Bile Acids and Salts
10 Liver Extracts
11 Protein C Inhibitor

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Second-line Therapy of Unresectable Cholangiocarcinoma by RADIOEMBOLIZATION Terminated NCT01383746 Phase 1, Phase 2
2 A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384 Completed NCT02963077 Phase 1 A4250;CRC (A3384);Questran;Placebo
3 ABCB4 Gene Mutations in Intrahepatic Cholestasis of Pregnancy and Controls Completed NCT00700232
4 Evaluating the Genetic Causes and Progression of Cholestatic Liver Diseases (LOGIC) Recruiting NCT00571272

Search 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:

id Genetic test Affiliating Genes
1 Progressive Familial Intrahepatic Cholestasis 4 29
2 Cholestasis, Progressive Familial Intrahepatic 4 24 TJP2

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic 4

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

39
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 13)
id 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.885delC (p.Ser296Alafs) deletion Pathogenic rs587777519 GRCh37 Chromosome 9, 71836345: 71836345
3 TJP2 NM_004817.3(TJP2): c.1361delC (p.Ala454Glyfs) deletion Pathogenic rs587777520 GRCh37 Chromosome 9, 71842938: 71842938
4 TJP2 NM_004817.3(TJP2): c.1992-2A> G single nucleotide variant Pathogenic rs587777521 GRCh37 Chromosome 9, 71851863: 71851863
5 TJP2 NM_004817.3(TJP2): c.3408_3573del166 (p.Ser1136Argfs) deletion Pathogenic GRCh37 Chromosome 9, 71869125: 71869290
6 TJP2 NM_004817.3(TJP2): c.2668-1G> T single nucleotide variant Pathogenic rs864321695 GRCh37 Chromosome 9, 71862927: 71862927
7 TJP2 NM_004817.3(TJP2): c.2438dupT (p.Asn814Glnfs) duplication Pathogenic rs864321696 GRCh37 Chromosome 9, 71854935: 71854935
8 TJP2 NM_004817.3(TJP2): c.817delG (p.Ala273Profs) deletion Pathogenic rs864321697 GRCh37 Chromosome 9, 71836277: 71836277
9 TJP2 NM_004817.3(TJP2): c.1697T> A (p.Leu566Ter) single nucleotide variant Pathogenic rs886042381 GRCh37 Chromosome 9, 71849380: 71849380
10 TJP2 NM_004817.3(TJP2): c.498dupG (p.Arg167Alafs) duplication Pathogenic rs886044313 GRCh37 Chromosome 9, 71835958: 71835958
11 TJP2 NM_004817.3(TJP2): c.1243delT (p.Ser415Leufs) deletion Pathogenic rs1057518679 GRCh37 Chromosome 9, 71842713: 71842713
12 TJP2 NG_016342.1: g.(102053_104579)_(123841_130382)dup duplication Pathogenic GRCh38 Chromosome 9, 69218360: 69246689
13 TJP2 NM_004817.3(TJP2): c.1210G> A (p.Asp404Asn) single nucleotide variant Likely pathogenic rs1060499649 GRCh38 Chromosome 9, 69226175: 69226175

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

GO Terms for Cholestasis, Progressive Familial Intrahepatic 4

Sources for Cholestasis, Progressive Familial Intrahepatic 4

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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