PFIC5
MCID: CHL091
MIFTS: 40

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 58 76 30 6
Pfic5 58 12 60 76
Progressive Familial Intrahepatic Cholestasis 5 12 15
Nr1h4 Deficiency 12 60
Cholestasis, Intrahepatic, Familial, Progressive, Type 5 41
Progressive Familial Intrahepatic Cholestasis Type 5 60

Characteristics:

OMIM:

58
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:

33
cholestasis, progressive familial intrahepatic, 5:
Onset and clinical course rapidly progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Cholestasis, Progressive Familial Intrahepatic, 5

OMIM : 58 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)

MalaCards based summary : Cholestasis, Progressive Familial Intrahepatic, 5, also known as pfic5, is related to atp8b1 deficiency and cholestasis, progressive familial intrahepatic, 2. 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 Cytochrome P450 - arranged by substrate type and Drug metabolism - cytochrome P450. Affiliated tissues include liver, 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 : 76 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 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, 5 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)
# Related Disease Score Top Affiliating Genes
1 atp8b1 deficiency 10.1 ABCB11 NR1H4
2 cholestasis, progressive familial intrahepatic, 2 9.9 ABCB11 NR0B2 NR1H4
3 progressive familial intrahepatic cholestasis 9.9 ABCB11 NR1H4
4 cholestasis, progressive familial intrahepatic, 1 9.9 ABCB11 NR0B2 NR1H4
5 phenytoin toxicity 9.9 CYP2C19 CYP2C9
6 esophageal candidiasis 9.9 CYP2C19 CYP2C9
7 autosomal dominant non-syndromic intellectual disability 2 9.9 NR1I2 NR1I3
8 autosomal dominant non-syndromic intellectual disability 3 9.9 NR1I2 NR1I3
9 multiple chemical sensitivity 9.9 CYP2C19 CYP2C9
10 drug-induced hepatitis 9.8 CYP2C19 CYP2C9
11 clopidogrel resistance 9.8 CYP2C19 CYP2C9
12 sclerosing cholangitis 9.7 ABCB11 NR1H4 NR1I2
13 cerebrotendinous xanthomatosis 9.6 NR1H4 NR1I2
14 biliary tract disease 9.5 ABCB11 NR1H4 NR1I2 NR1I3
15 bile duct disease 9.5 ABCB11 NR0B2 NR1H4 NR1I2
16 cholestasis 9.3 ABCB11 NR0B2 NR1H4 NR1I2 NR1I3
17 intrahepatic cholestasis of pregnancy 9.3 ABCB11 NR0B2 NR1H4 NR1I2 NR1I3

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:

33 (show all 9)
# Description HPO Frequency HPO Source Accession
1 edema 33 occasional (7.5%) HP:0000969
2 failure to thrive 33 HP:0001508
3 hypoglycemia 33 HP:0001943
4 cirrhosis 33 HP:0001394
5 jaundice 33 HP:0000952
6 hepatic failure 33 HP:0001399
7 hyperammonemia 33 HP:0001987
8 prolonged prothrombin time 33 HP:0008151
9 elevated hepatic transaminase 33 HP:0002910

Symptoms via clinical synopsis from OMIM:

58
Growth Other:
failure to thrive

Abdomen Liver:
cirrhosis
liver failure
fibrosis
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

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

47
# Description MGI Source Accession Score Top Affiliating Genes
1 liver/biliary system MP:0005370 9.02 ABCB11 NR0B2 NR1H4 NR1I2 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 30 NR1H4

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic, 5

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

42
Liver

Publications for Cholestasis, Progressive Familial Intrahepatic, 5

Variations for Cholestasis, Progressive Familial Intrahepatic, 5

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

6
# Gene Variation Type Significance SNP ID Assembly Location
1 NR1H4 NM_005123.3(NR1H4): c.419_420insAAA (p.Tyr139_Asn140insLys) insertion Pathogenic rs879255644 GRCh37 Chromosome 12, 100904895: 100904896
2 NR1H4 NM_005123.3(NR1H4): c.419_420insAAA (p.Tyr139_Asn140insLys) insertion Pathogenic rs879255644 GRCh38 Chromosome 12, 100511117: 100511118
3 NR1H4 NM_005123.3(NR1H4): c.526C> T (p.Arg176Ter) single nucleotide variant Pathogenic rs113090017 GRCh37 Chromosome 12, 100926316: 100926316
4 NR1H4 NM_005123.3(NR1H4): c.526C> T (p.Arg176Ter) single nucleotide variant Pathogenic rs113090017 GRCh38 Chromosome 12, 100532538: 100532538
5 NR1H4 NR1H4, 31.7-KB DEL deletion Pathogenic

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:

(show all 19)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.96 CYP2B6 CYP2C18 CYP2C19 CYP2C9 NR1H4
2
Show member pathways
12.59 CYP2B6 CYP2C18 CYP2C19 CYP2C9
3
Show member pathways
11.78 CYP2B6 CYP2C19 CYP2C9
4 11.76 CYP2C18 CYP2C19 CYP2C9
5
Show member pathways
11.74 ABCB11 CYP2C19 CYP2C9
6
Show member pathways
11.62 NR0B2 NR1H4 NR1I2 NR1I3
7 11.53 ABCB11 NR0B2 NR1H4
8
Show member pathways
11.51 CYP2B6 CYP2C18 CYP2C19 CYP2C9
9
Show member pathways
11.5 CYP2B6 CYP2C19 CYP2C9
10 11.34 CYP2B6 CYP2C19 CYP2C9
11
Show member pathways
11.32 CYP2C19 CYP2C9
12
Show member pathways
11.2 CYP2B6 CYP2C19 CYP2C9
13
Show member pathways
11.16 CYP2B6 CYP2C19 CYP2C9 NR1I2 NR1I3
14 11.06 CYP2B6 CYP2C19 CYP2C9 NR1I3
15 10.9 CYP2B6 CYP2C9
16 10.86 ABCB11 NR0B2 NR1H4
17 10.69 ABCB11 NR1H4 NR1I2 NR1I3
18 10.66 CYP2B6 CYP2C9
19 10.64 ABCB11 CYP2B6 CYP2C9 NR1H4 NR1I2 NR1I3

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 endoplasmic reticulum membrane GO:0005789 9.56 CYP2B6 CYP2C18 CYP2C19 CYP2C9
2 intracellular membrane-bounded organelle GO:0043231 9.46 CYP2B6 CYP2C18 CYP2C19 CYP2C9
3 RNA polymerase II transcription factor complex GO:0090575 9.13 NR1H4 NR1I2 NR1I3
4 organelle membrane GO:0031090 8.92 CYP2B6 CYP2C18 CYP2C19 CYP2C9

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.83 CYP2B6 CYP2C18 CYP2C19 CYP2C9
2 transcription initiation from RNA polymerase II promoter GO:0006367 9.73 NR0B2 NR1H4 NR1I2 NR1I3
3 steroid metabolic process GO:0008202 9.67 CYP2B6 CYP2C19 CYP2C9 NR1I2
4 intracellular receptor signaling pathway GO:0030522 9.63 NR1H4 NR1I2 NR1I3
5 steroid hormone mediated signaling pathway GO:0043401 9.62 NR0B2 NR1H4 NR1I2 NR1I3
6 drug metabolic process GO:0017144 9.58 CYP2B6 CYP2C19 CYP2C9
7 organic acid metabolic process GO:0006082 9.56 CYP2B6 CYP2C18 CYP2C19 CYP2C9
8 xenobiotic metabolic process GO:0006805 9.55 CYP2B6 CYP2C18 CYP2C19 CYP2C9 NR1I2
9 bile acid and bile salt transport GO:0015721 9.51 ABCB11 NR1H4
10 omega-hydroxylase P450 pathway GO:0097267 9.49 CYP2C19 CYP2C9
11 monoterpenoid metabolic process GO:0016098 9.48 CYP2C19 CYP2C9
12 epoxygenase P450 pathway GO:0019373 9.26 CYP2B6 CYP2C18 CYP2C19 CYP2C9
13 exogenous drug catabolic process GO:0042738 9.02 CYP2B6 CYP2C18 CYP2C19 CYP2C9 NR1I2

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

(show all 21)
# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.85 CYP2B6 CYP2C18 CYP2C19 CYP2C9
2 transcription factor binding GO:0008134 9.81 NR0B2 NR1H4 NR1I2 NR1I3
3 transcription coactivator activity GO:0003713 9.77 NR1H4 NR1I2 NR1I3
4 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.76 NR1H4 NR1I2 NR1I3
5 signaling receptor activity GO:0038023 9.75 NR1H4 NR1I2 NR1I3
6 heme binding GO:0020037 9.73 CYP2B6 CYP2C18 CYP2C19 CYP2C9
7 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.71 NR1H4 NR1I2 NR1I3
8 iron ion binding GO:0005506 9.71 CYP2B6 CYP2C18 CYP2C19 CYP2C9
9 transcription regulatory region sequence-specific DNA binding GO:0000976 9.67 NR1H4 NR1I2 NR1I3
10 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016705 9.67 CYP2B6 CYP2C18 CYP2C19 CYP2C9
11 nuclear receptor transcription coactivator activity GO:0030374 9.65 NR1H4 NR1I2 NR1I3
12 nuclear receptor activity GO:0004879 9.63 NR1H4 NR1I2 NR1I3
13 monooxygenase activity GO:0004497 9.62 CYP2B6 CYP2C18 CYP2C19 CYP2C9
14 drug binding GO:0008144 9.6 CYP2C9 NR1I2
15 oxygen binding GO:0019825 9.57 CYP2C18 CYP2C19
16 steroid hormone receptor activity GO:0003707 9.56 NR0B2 NR1H4 NR1I2 NR1I3
17 retinoid X receptor binding GO:0046965 9.52 NR0B2 NR1H4
18 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen GO:0016712 9.46 CYP2B6 CYP2C18 CYP2C19 CYP2C9
19 steroid hydroxylase activity GO:0008395 9.26 CYP2B6 CYP2C18 CYP2C19 CYP2C9
20 arachidonic acid epoxygenase activity GO:0008392 8.92 CYP2B6 CYP2C18 CYP2C19 CYP2C9
21 metal ion binding GO:0046872 10.1 CYP2B6 CYP2C18 CYP2C19 CYP2C9 NR1H4 NR1I2

Sources for Cholestasis, Progressive Familial Intrahepatic, 5

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
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34 ICD10
35 ICD10 via Orphanet
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45 MeSH
46 MESH via Orphanet
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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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