PFIC5
MCID: CHL091
MIFTS: 39

Cholestasis, Progressive Familial Intrahepatic, 5 (PFIC5)

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

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic, 5

MalaCards integrated aliases for Cholestasis, Progressive Familial Intrahepatic, 5:

Name: Cholestasis, Progressive Familial Intrahepatic, 5 57 72 29 6
Pfic5 57 12 58 72
Progressive Familial Intrahepatic Cholestasis 5 12 15
Nr1h4 Deficiency 12 58
Cholestasis, Intrahepatic, Familial, Progressive, Type 5 39
Progressive Familial Intrahepatic Cholestasis Type 5 58

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
rapid progression
two unrelated families have been reported (last curated july 2016)
onset at birth or in the neonatal period
fatal unless liver transplant is performed


HPO:

31
cholestasis, progressive familial intrahepatic, 5:
Inheritance autosomal recessive inheritance
Onset and clinical course rapidly progressive


Classifications:

Orphanet: 58  
Rare hepatic diseases
Inborn errors of metabolism


Summaries for Cholestasis, Progressive Familial Intrahepatic, 5

OMIM® : 57 Progressive familial intrahepatic cholestasis-5 (PFIC5) is an autosomal recessive severe liver disorder characterized by onset of intralobular cholestasis in the neonatal period. The disease is rapidly progressive, leading to liver failure and death if liver transplant is not performed. Other features include abnormal liver enzymes, low to normal gamma-glutamyl transferase (GGT) activity, increased alpha-fetoprotein, and a vitamin K-independent coagulopathy (summary by Gomez-Ospina et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of PFIC, see PFIC1 (211600). (617049) (Updated 20-May-2021)

MalaCards based summary : Cholestasis, Progressive Familial Intrahepatic, 5, also known as pfic5, is related to familial intrahepatic cholestasis and liver disease. An important gene associated with Cholestasis, Progressive Familial Intrahepatic, 5 is NR1H4 (Nuclear Receptor Subfamily 1 Group H Member 4), and among its related pathways/superpathways are Nuclear Receptor transcription pathway and Bile secretion. Affiliated tissues include liver and heart, and related phenotypes are edema and failure to thrive

Disease Ontology : 12 A progressive familial intrahepatic cholestasis characterized by autosomal recessive inheritance of intralobular cholestasis with onset in the neonatal period that has material basis in mutation in the NR1H4 gene on chromosome 12q.

UniProtKB/Swiss-Prot : 72 Cholestasis, progressive familial intrahepatic, 5: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC5 is an autosomal recessive, severe form characterized by onset of intralobular cholestasis in the neonatal period.

Related Diseases for Cholestasis, Progressive Familial Intrahepatic, 5

Diseases in the 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 Progressive Familial Intrahepatic Cholestasis
Myo5b-Related Progressive Familial Intrahepatic Cholestasis

Diseases related to Cholestasis, Progressive Familial Intrahepatic, 5 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 38)
# Related Disease Score Top Affiliating Genes
1 familial intrahepatic cholestasis 29.2 TJP2 NR1H4 ATP8B1 ABCB4 ABCB11
2 liver disease 29.1 TJP2 NR1H4 ATP8B1 ABCB4 ABCB11
3 progressive familial intrahepatic cholestasis 28.7 TJP2 NR1H4 NR0B2 ATP8B1 ABCB4 ABCB11
4 cholestasis 28.1 TJP2 NR1I3 NR1H4 NR0B2 ATP8B1 ABCB4
5 non-alcoholic fatty liver disease 10.1
6 hepatic vascular disease 9.9 NR1H4 ABCB4
7 pericholangitis 9.9 ABCB4 ABCB11
8 dubin-johnson syndrome 9.8 ATP8B1 ABCB11
9 autosomal dominant non-syndromic intellectual disability 3 9.8 ABCB4 ABCB11
10 cholelithiasis 9.8 NR1H4 ABCB4
11 common bile duct disease 9.8 ABCB4 ABCB11
12 cholestasis, intrahepatic, of pregnancy 3 9.8 ABCB4 ABCB11
13 atp8b1 deficiency 9.8 NR1H4 ATP8B1 ABCB11
14 cholangitis 9.7 NR1H4 ABCB4 ABCB11
15 heart defects, congenital, and other congenital anomalies 9.7 NR1H4 NR0B2 ABCB11
16 bile duct cysts 9.7 ATP8B1 ABCB4 ABCB11
17 extrahepatic cholestasis 9.7 NR1H4 ABCB4 ABCB11
18 alagille syndrome 1 9.7 ATP8B1 ABCB4 ABCB11
19 sclerosing cholangitis 9.7 NR1H4 ABCB4 ABCB11
20 gallbladder disease 9.7 NR1H4 ABCB4 ABCB11
21 sitosterolemia 9.7 ATP8B1 ABCB4 ABCB11
22 biliary atresia 9.5 NR1H4 ATP8B1 ABCB4 ABCB11
23 cholangitis, primary sclerosing 9.4 NR1H4 NR0B2 ABCB4 ABCB11
24 crigler-najjar syndrome, type i 9.4 NR1I3 ABCB11
25 bile acid synthesis defect, congenital, 2 9.3 NR1I3 NR1H4 NR0B2 ABCB11
26 cholestasis, progressive familial intrahepatic, 4 9.3 TJP2 NR1H4 ATP8B1 ABCB4 ABCB11
27 cholestasis, benign recurrent intrahepatic, 2 9.3 TJP2 NR1H4 ATP8B1 ABCB4 ABCB11
28 cholestasis, progressive familial intrahepatic, 3 9.3 TJP2 NR1H4 ATP8B1 ABCB4 ABCB11
29 primary biliary cholangitis 9.2 NR1I3 NR1H4 ABCB4 ABCB11
30 bile duct disease 9.2 NR1H4 NR0B2 ATP8B1 ABCB4 ABCB11
31 cholestasis, intrahepatic, of pregnancy, 1 9.1 NR1I3 NR1H4 ATP8B1 ABCB4 ABCB11
32 intrahepatic cholestasis of pregnancy 9.1 NR1I3 NR1H4 ATP8B1 ABCB4 ABCB11
33 bilirubin metabolic disorder 9.1 NR1I3 NR1H4 ATP8B1 ABCB4 ABCB11
34 cholestasis, progressive familial intrahepatic, 2 9.0 TJP2 NR1H4 NR0B2 ATP8B1 ABCB4 ABCB11
35 cholestasis, progressive familial intrahepatic, 1 9.0 TJP2 NR1H4 NR0B2 ATP8B1 ABCB4 ABCB11
36 cholestasis, benign recurrent intrahepatic, 1 9.0 TJP2 NR1H4 NR0B2 ATP8B1 ABCB4 ABCB11
37 leber plus disease 9.0 NR1I3 NR1H4 NR0B2 ABCB4 ABCB11
38 biliary tract disease 8.8 NR1I3 NR1H4 NR0B2 ATP8B1 ABCB4 ABCB11

Graphical network of the top 20 diseases related to Cholestasis, Progressive Familial Intrahepatic, 5:



Diseases related to Cholestasis, Progressive Familial Intrahepatic, 5

Symptoms & Phenotypes for Cholestasis, Progressive Familial Intrahepatic, 5

Human phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 5:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 edema 31 occasional (7.5%) HP:0000969
2 failure to thrive 31 HP:0001508
3 hypoglycemia 31 HP:0001943
4 elevated hepatic transaminase 31 HP:0002910
5 cirrhosis 31 HP:0001394
6 jaundice 31 HP:0000952
7 hepatic failure 31 HP:0001399
8 hyperammonemia 31 HP:0001987
9 prolonged prothrombin time 31 HP:0008151

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive

Abdomen Liver:
cirrhosis
fibrosis
liver failure
ductal reaction seen on liver biopsy
intralobular cholestasis
more
Hematology:
prolonged prothrombin time
vitamin k-independent coagulopathy
increased inr
decreased levels of factor v and vii

Laboratory Abnormalities:
hypoglycemia
hyperammonemia
abnormal liver enzymes
increased alpha-fetoprotein
ggt is not increased

Skin Nails Hair Skin:
jaundice

Prenatal Manifestations Amniotic Fluid:
hydrops (1 patient)

Clinical features from OMIM®:

617049 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 5 according to GeneCards Suite gene sharing:

26 (show all 11)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.53 NR1I3 TJP2
2 Decreased viability GR00221-A-2 9.53 NR1H4 NR1I3 TJP2
3 Decreased viability GR00221-A-3 9.53 TJP2
4 Decreased viability GR00221-A-4 9.53 NR1H4 TJP2
5 Decreased viability GR00240-S-1 9.53 TJP2
6 Decreased viability GR00249-S 9.53 NR1H4 NR1I3
7 Decreased viability GR00301-A 9.53 NR1I3
8 Decreased viability GR00342-S-3 9.53 TJP2
9 Decreased viability GR00381-A-1 9.53 TJP2
10 Decreased viability GR00386-A-1 9.53 NR1I3
11 Decreased viability GR00402-S-2 9.53 TJP2

MGI Mouse Phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 5:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.5 ABCB11 ABCB4 ATP8B1 NR0B2 NR1H4 NR1I3
2 liver/biliary system MP:0005370 9.1 ABCB11 ABCB4 ATP8B1 NR0B2 NR1H4 NR1I3

Drugs & Therapeutics for Cholestasis, Progressive Familial Intrahepatic, 5

Search Clinical Trials , NIH Clinical Center for Cholestasis, Progressive Familial Intrahepatic, 5

Genetic Tests for Cholestasis, Progressive Familial Intrahepatic, 5

Genetic tests related to Cholestasis, Progressive Familial Intrahepatic, 5:

# Genetic test Affiliating Genes
1 Cholestasis, Progressive Familial Intrahepatic, 5 29 NR1H4

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic, 5

MalaCards organs/tissues related to Cholestasis, Progressive Familial Intrahepatic, 5:

40
Liver, Heart

Publications for Cholestasis, Progressive Familial Intrahepatic, 5

Articles related to Cholestasis, Progressive Familial Intrahepatic, 5:

# Title Authors PMID Year
1
Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis. 6 57
26888176 2016
2
A novel heterozygous NR1H4 termination codon mutation in idiopathic infantile cholestasis. 6 57
21633855 2012
3
Familial intrahepatic cholestasis: New and wide perspectives. 61
31105019 2019
4
Constitutive Androstane Receptor Differentially Regulates Bile Acid Homeostasis in Mouse Models of Intrahepatic Cholestasis. 61
30620001 2019
5
Xenobiotic Nuclear Receptor Signaling Determines Molecular Pathogenesis of Progressive Familial Intrahepatic Cholestasis. 61
29718219 2018

Variations for Cholestasis, Progressive Familial Intrahepatic, 5

ClinVar genetic disease variations for Cholestasis, Progressive Familial Intrahepatic, 5:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NR1H4 NM_001206979.2(NR1H4):c.419_420insAAA (p.Asn140_Ala141insLys) Insertion Pathogenic 219162 rs879255644 GRCh37: 12:100904893-100904894
GRCh38: 12:100511115-100511116
2 NR1H4 NR1H4, 31.7-KB DEL Deletion Pathogenic 253139 GRCh37:
GRCh38:
3 NR1H4 NM_001206979.2(NR1H4):c.526C>T (p.Arg176Ter) SNV Pathogenic 219164 rs113090017 GRCh37: 12:100926316-100926316
GRCh38: 12:100532538-100532538
4 NR1H4 NM_001206979.2(NR1H4):c.547C>T (p.Arg183Ter) SNV Pathogenic 498806 rs1555335324 GRCh37: 12:100926337-100926337
GRCh38: 12:100532559-100532559
5 NR1H4 NM_001206979.2(NR1H4):c.1034del (p.Pro345fs) Deletion Likely pathogenic 804467 rs1593114820 GRCh37: 12:100934551-100934551
GRCh38: 12:100540773-100540773

Expression for Cholestasis, Progressive Familial Intrahepatic, 5

Search GEO for disease gene expression data for Cholestasis, Progressive Familial Intrahepatic, 5.

Pathways for Cholestasis, Progressive Familial Intrahepatic, 5

Pathways related to Cholestasis, Progressive Familial Intrahepatic, 5 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.45 NR1I3 NR1H4 NR0B2
2 11.41 NR1H4 NR0B2 ABCB4 ABCB11
3 10.8 NR1I3 NR1H4 ABCB4 ABCB11
4 10.66 NR1I3 NR1H4 ABCB11
5 10.2 NR1H4 NR0B2 ABCB4 ABCB11

GO Terms for Cholestasis, Progressive Familial Intrahepatic, 5

Cellular components related to Cholestasis, Progressive Familial Intrahepatic, 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.43 TJP2 NR1I3 NR1H4 NR0B2 ATP8B1 ABCB4
2 apical plasma membrane GO:0016324 9.33 ATP8B1 ABCB4 ABCB11
3 intercellular canaliculus GO:0046581 8.62 ABCB4 ABCB11

Biological processes related to Cholestasis, Progressive Familial Intrahepatic, 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription initiation from RNA polymerase II promoter GO:0006367 9.5 NR1I3 NR1H4 NR0B2
2 cholesterol homeostasis GO:0042632 9.46 NR1H4 ABCB11
3 lipid homeostasis GO:0055088 9.43 ABCB4 ABCB11
4 intracellular receptor signaling pathway GO:0030522 9.4 NR1I3 NR1H4
5 phospholipid translocation GO:0045332 9.37 ATP8B1 ABCB4
6 drug transmembrane transport GO:0006855 9.26 ATP8B1 ABCB11
7 cellular response to bile acid GO:1903413 9.16 NR1H4 ABCB4
8 bile acid metabolic process GO:0008206 9.13 NR1H4 ATP8B1 ABCB11
9 bile acid and bile salt transport GO:0015721 8.92 NR1H4 NR0B2 ATP8B1 ABCB11

Molecular functions related to Cholestasis, Progressive Familial Intrahepatic, 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear receptor activity GO:0004879 9.16 NR1I3 NR1H4
2 ATPase activity, coupled to transmembrane movement of substances GO:0042626 8.96 ABCB4 ABCB11
3 retinoid X receptor binding GO:0046965 8.62 NR1H4 NR0B2

Sources for Cholestasis, Progressive Familial Intrahepatic, 5

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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