PFIC1
MCID: CHL080
MIFTS: 46

Cholestasis, Progressive Familial Intrahepatic 1 (PFIC1) malady

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

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic 1

Aliases & Descriptions for Cholestasis, Progressive Familial Intrahepatic 1:

Name: Cholestasis, Progressive Familial Intrahepatic 1 54 13
Byler Disease 50 24 25 56 66 52
Pfic1 50 24 56 66
Progressive Familial Intrahepatic Cholestasis 50 25 56
Fic1 Deficiency 24 25 56
Cholestasis, Progressive Familial Intrahepatic, 1 54 66
Byler Syndrome 24 25
Progressive Familial Intrahepatic Cholestasis, Type 1 24
Progressive Familial Intrahepatic Cholestasis Type 1 56
Cholestasis, Progressive Familial Intrahepatic 3 69
Progressive Familial Intrahepatic Cholestasis 1 50
Familial Intraheparic Cholestasis 1 Deficiency 24
Low Γ-Gt Familial Intrahepatic Cholestasis 25
Abcb11-Related Intrahepatic Cholestasis 25
Atp8b1-Related Intrahepatic Cholestasis 25
Abcb4-Related Intrahepatic Cholestasis 25
Progressive Intrahepatic Cholestasis 69
Cholestasis, Fatal Intrahepatic 50
Greenland Childhood Cholestasis 24
Greenland Familial Cholestasis 24
Fatal Intrahepatic Cholestasis 66
Severe Atp8b1 Deficiency 50
Byler's Disease 50
Mdr3 Deficiency 25
Bsep Deficiency 25
Pfic-1 24
Pfic 56

Characteristics:

Orphanet epidemiological data:

56
progressive familial intrahepatic cholestasis
Inheritance: Autosomal recessive; Age of onset: Adolescent,Childhood,Infancy,Neonatal;
progressive familial intrahepatic cholestasis type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

HPO:

32
cholestasis, progressive familial intrahepatic 1:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

OMIM 54 211600
UMLS via Orphanet 70 C0268312
ICD10 via Orphanet 34 K76.8
MESH via Orphanet 43 C535933
MedGen 40 C0268312
MeSH 42 D002780

Summaries for Cholestasis, Progressive Familial Intrahepatic 1

OMIM : 54 Progressive familial intrahepatic cholestasis is a heterogeneous group of autosomal recessive liver disorders... (211600) more...

MalaCards based summary : Cholestasis, Progressive Familial Intrahepatic 1, also known as byler disease, is related to abcb11-related intrahepatic cholestasis and atp8b1-related intrahepatic cholestasis, and has symptoms including failure to thrive, splenomegaly and hepatomegaly. An important gene associated with Cholestasis, Progressive Familial Intrahepatic 1 is ATP8B1 (ATPase Phospholipid Transporting 8B1), and among its related pathways/superpathways are Synthesis of bile acids and bile salts and Nuclear Receptors in Lipid Metabolism and Toxicity. The drugs Liver Extracts and Bile Acids and Salts have been mentioned in the context of this disorder. Affiliated tissues include liver and bone, and related phenotypes are Decreased vaccinia virus (VACV-LREV ) gene expression and growth/size/body region

Genetics Home Reference : 25 Progressive familial intrahepatic cholestasis (PFIC) is a disorder that causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete a digestive fluid called bile. The buildup of bile in liver cells causes liver disease in affected individuals.

UniProtKB/Swiss-Prot : 66 Cholestasis, progressive familial intrahepatic, 1: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood.

Wikipedia : 71 Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions... more...

Related Diseases for Cholestasis, Progressive Familial Intrahepatic 1

Diseases in the Intrahepatic Cholestasis family:

Cholestasis, Progressive Familial Intrahepatic 2 Cholestasis, Benign Recurrent Intrahepatic, 2
Cholestasis, Progressive Familial Intrahepatic 3 Cholestasis, Progressive Familial Intrahepatic 4
Cholestasis, Progressive Familial Intrahepatic 1 Cholestasis, Benign Recurrent Intrahepatic
Abcb11-Related Intrahepatic Cholestasis Atp8b1-Related Intrahepatic Cholestasis
Cholestasis, Progressive Familial Intrahepatic 5 Myo5b-Related Progressive Familial Intrahepatic Cholestasis

Diseases related to Cholestasis, Progressive Familial Intrahepatic 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 30)
id Related Disease Score Top Affiliating Genes
1 abcb11-related intrahepatic cholestasis 12.2
2 atp8b1-related intrahepatic cholestasis 12.2
3 myo5b-related progressive familial intrahepatic cholestasis 12.1
4 cholestasis, progressive familial intrahepatic 3 11.9
5 cholestasis, progressive familial intrahepatic 2 11.9
6 cholestasis, benign recurrent intrahepatic 11.2
7 atp8b1 deficiency 10.9
8 bile acid synthesis defect, congenital, 1 10.8
9 borderline leprosy 10.0 ABCB4 NR1H4
10 cholestasis 10.0
11 intrahepatic cholestasis 10.0
12 autosomal dominant tubulointerstitial kidney disease, muc1-related 10.0 ABCB11 ATP8B1 NR1H4
13 marfan syndrome/loeys-dietz syndrome/familial thoracic aortic aneurysms and dissections 10.0 ABCB11 ABCB4 ATP8B1
14 acute cholangitis 9.9 ABCB11 ABCB4
15 dyserythropoietic anemia, congenital, type ii 9.9 ABCB4 ATP8B1 JAG1
16 microcephaly, progressive, seizures, and cerebral and cerebellar atrophy 9.9 ABCB4 GGT1
17 amyotrophic lateral sclerosis 3 9.8 ABCB11 ABCB4 ATP8B1 NR1H4
18 patent foramen ovale 9.8 JAG1 NR1H4 SLC10A2
19 ringed hair 9.8 GGT1 JAG1
20 osteomalacia 9.8
21 pseudoarthrosis 9.8 ABCB4 GGT1 NR1H4
22 bacterial meningitis 9.7 ABCB11 ABCB4 GGT1
23 gallbladder disease 1 9.7 ABCB11 ABCB4 ATP8B1 JAG1
24 cholestasis, benign recurrent intrahepatic, 2 9.7 ABCB11 ABCB4 ATP8B1 MYO5B NR1H4
25 lymphoid leukemia 9.6 ABCB11 ABCB4 ATP8B1 GGT1
26 heart aneurysm 9.5 ABCB11 ABCB4 ATP8B1 GGT1 NR1H4
27 gastrointestinal adenoma 9.3 ABCB11 ABCB4 ATP8B1 GGT1 NR1H4 SLC10A2
28 chronic rheumatic pericarditis 9.1 ABCB11 ABCB4 ATP8B1 GGT1 JAG1 NR1H4
29 eclampsia 9.1 ABCB11 ABCB4 ATP8B1 GGT1 JAG1 NR1H4
30 cholestasis, intrahepatic, of pregnancy, 1 8.9 ABCB11 ABCB4 ATP8B1 GGT1 JAG1 MYO5B

Graphical network of the top 20 diseases related to Cholestasis, Progressive Familial Intrahepatic 1:



Diseases related to Cholestasis, Progressive Familial Intrahepatic 1

Symptoms & Phenotypes for Cholestasis, Progressive Familial Intrahepatic 1

Symptoms by clinical synopsis from OMIM:

211600

Clinical features from OMIM:

211600

Human phenotypes related to Cholestasis, Progressive Familial Intrahepatic 1:

56 32 (show all 21)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 56 32 Very frequent (99-80%) HP:0001508
2 splenomegaly 56 32 Very frequent (99-80%) HP:0001744
3 hepatomegaly 56 32 Very frequent (99-80%) HP:0002240
4 delayed skeletal maturation 56 32 Frequent (79-30%) HP:0002750
5 malabsorption 56 32 Very frequent (99-80%) HP:0002024
6 short stature 56 32 Very frequent (99-80%) HP:0004322
7 cognitive impairment 56 32 Very frequent (99-80%) HP:0100543
8 neoplasm 56 32 Occasional (29-5%) HP:0002664
9 reduced bone mineral density 56 32 Frequent (79-30%) HP:0004349
10 jaundice 56 32 Very frequent (99-80%) HP:0000952
11 abnormality of thrombocytes 56 32 Frequent (79-30%) HP:0001872
12 hypocalcemia 56 32 Frequent (79-30%) HP:0002901
13 abnormality of coagulation 56 32 Very frequent (99-80%) HP:0001928
14 pruritus 32 HP:0000989
15 diarrhea 32 HP:0002014
16 cirrhosis 32 HP:0001394
17 cholestasis 56 Very frequent (99-80%)
18 severe short stature 32 HP:0003510
19 conjugated hyperbilirubinemia 32 HP:0002908
20 fat malabsorption 32 HP:0002630
21 intrahepatic cholestasis with episodic jaundice 32 HP:0006575

UMLS symptoms related to Cholestasis, Progressive Familial Intrahepatic 1:


diarrhea, icterus, pruritus

GenomeRNAi Phenotypes related to Cholestasis, Progressive Familial Intrahepatic 1 according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased vaccinia virus (VACV-LREV ) gene expression GR00351-A-2 8.62 ATP8B1 JAG1

MGI Mouse Phenotypes related to Cholestasis, Progressive Familial Intrahepatic 1:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.76 ATP8B1 GGT1 JAG1 MYO5B NR1H4 SLC10A2
2 digestive/alimentary MP:0005381 9.65 ABCB4 JAG1 MYO5B NR1H4 SLC10A2
3 homeostasis/metabolism MP:0005376 9.56 ABCB11 ABCB4 ATP8B1 GGT1 JAG1 MYO5B
4 liver/biliary system MP:0005370 9.1 ABCB11 ABCB4 ATP8B1 JAG1 NR1H4 SLC10A2

Drugs & Therapeutics for Cholestasis, Progressive Familial Intrahepatic 1

Drugs for Cholestasis, Progressive Familial Intrahepatic 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 20)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Liver Extracts Phase 2,Phase 1
2 Bile Acids and Salts Phase 2
3
Menthol Approved Phase 1 2216-51-5 16666
4 Cholestyramine Resin Phase 1
5 Hypolipidemic Agents Phase 1
6 Anticholesteremic Agents Phase 1
7 Lipid Regulating Agents Phase 1
8 Antimetabolites Phase 1
9 Cola Nutraceutical Phase 1
10
Iron Approved 7439-89-6 23925
11
Pancrelipase Approved 53608-75-6
12
Glycerol Approved, Experimental 56-81-5 753
13 Estrogens
14 pancreatin
15
Bilirubin 635-65-4 5280352
16 Alpha 1-Antitrypsin
17 Hematinics
18 Protein C Inhibitor
19 4-phenylbutyric acid
20 Protective Agents

Interventional clinical trials:

(show all 14)
id Name Status NCT ID Phase
1 Open Label Study to Evaluate Efficacy and Long Term Safety of LUM001 in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic Cholestasis Active, not recruiting NCT02057718 Phase 2
2 Second-line Therapy of Unresectable Cholangiocarcinoma by RADIOEMBOLIZATION Terminated NCT01383746 Phase 1, Phase 2
3 A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384 Completed NCT02963077 Phase 1
4 An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects Completed NCT03082937 Phase 1
5 Genetic Epidemiology of Primary Biliary Cirrhosis (PBC) Recruiting NCT01161953 Phase 1
6 Sulfation of Bile Acids as a Biomarker for Hepatobiliary Diseases Unknown status NCT01200082
7 Validation of the Itch Reported Outcome (ItchRO) Diaries in Pediatric Cholestatic Liver Disease Completed NCT02131623
8 ABCB4 Gene Mutations in Intrahepatic Cholestasis of Pregnancy and Controls Completed NCT00700232
9 Evaluating the Genetic Causes and Progression of Cholestatic Liver Diseases (LOGIC) Recruiting NCT00571272
10 Shear Wave Sonoelastography in Pediatric Liver Fibrosis Recruiting NCT02372682
11 China Registry for Genetic / Metabolic Liver Diseases Recruiting NCT03131427
12 Buphenyl Therapy for Byler's Disease No longer available NCT01784718
13 Transition From Buphenyl to RAVICTI for the Therapy of Byler Disease No longer available NCT01949766
14 Expanded Access Protocol for an Intermediate Size Population - RAVICTI for Byler Disease Temporarily not available NCT02094222

Search NIH Clinical Center for Cholestasis, Progressive Familial Intrahepatic 1

Genetic Tests for Cholestasis, Progressive Familial Intrahepatic 1

Genetic tests related to Cholestasis, Progressive Familial Intrahepatic 1:

id Genetic test Affiliating Genes
1 Progressive Familial Intrahepatic Cholestasis, Type 1 24

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic 1

MalaCards organs/tissues related to Cholestasis, Progressive Familial Intrahepatic 1:

39
Liver, Bone

Publications for Cholestasis, Progressive Familial Intrahepatic 1

Variations for Cholestasis, Progressive Familial Intrahepatic 1

UniProtKB/Swiss-Prot genetic disease variations for Cholestasis, Progressive Familial Intrahepatic 1:

66 (show all 17)
id Symbol AA change Variation ID SNP ID
1 ATP8B1 p.Leu288Ser VAR_008809 rs121909099
2 ATP8B1 p.Gly308Val VAR_008810 rs28939685
3 ATP8B1 p.Ile661Thr VAR_008812 rs28939686
4 ATP8B1 p.Gly892Arg VAR_008813 rs121909098
5 ATP8B1 p.Asp554Asn VAR_015423 rs121909101
6 ATP8B1 p.Leu127Pro VAR_043046
7 ATP8B1 p.Ser403Tyr VAR_043053
8 ATP8B1 p.Arg412Pro VAR_043054
9 ATP8B1 p.Thr456Met VAR_043058 rs121909104
10 ATP8B1 p.Tyr500His VAR_043059 rs147642236
11 ATP8B1 p.His535Leu VAR_043061
12 ATP8B1 p.Asp688Gly VAR_043067
13 ATP8B1 p.Gly733Arg VAR_043069
14 ATP8B1 p.Phe853Ser VAR_043071 rs773092889
15 ATP8B1 p.Gly1040Arg VAR_043073
16 ATP8B1 p.Pro209Thr VAR_071045 rs515726138
17 ATP8B1 p.Ser1012Ile VAR_071046

ClinVar genetic disease variations for Cholestasis, Progressive Familial Intrahepatic 1:

6 (show all 16)
id Gene Variation Type Significance SNP ID Assembly Location
1 ATP8B1 NM_005603.4(ATP8B1): c.923G> T (p.Gly308Val) single nucleotide variant Pathogenic rs111033609 GRCh37 Chromosome 18, 55362420: 55362420
2 ATP8B1 NM_005603.4(ATP8B1): c.2674G> A (p.Gly892Arg) single nucleotide variant Pathogenic rs121909098 GRCh37 Chromosome 18, 55328439: 55328439
3 ATP8B1 NM_005603.4(ATP8B1): c.863T> C (p.Leu288Ser) single nucleotide variant Pathogenic rs121909099 GRCh37 Chromosome 18, 55362480: 55362480
4 ATP8B1 NM_005603.4(ATP8B1): c.2097+2T> C single nucleotide variant Pathogenic rs387906381 GRCh37 Chromosome 18, 55336548: 55336548
5 ATP8B1 ATP8B1, 1.4-KB DEL deletion Pathogenic
6 ATP8B1 NM_005603.4(ATP8B1): c.1982T> C (p.Ile661Thr) single nucleotide variant Pathogenic rs121909100 GRCh37 Chromosome 18, 55336665: 55336665
7 ATP8B1 NM_005603.4(ATP8B1): c.1660G> A (p.Asp554Asn) single nucleotide variant Pathogenic rs121909101 GRCh37 Chromosome 18, 55342225: 55342225
8 ATP8B1 NM_005603.4(ATP8B1): c.1367C> T (p.Thr456Met) single nucleotide variant Pathogenic rs121909104 GRCh37 Chromosome 18, 55355593: 55355593
9 ATP8B1 NM_005603.4(ATP8B1): c.1804C> T (p.Arg602Ter) single nucleotide variant Pathogenic rs121909105 GRCh37 Chromosome 18, 55342081: 55342081
10 ATP8B1 NM_005603.4(ATP8B1): c.1993G> T (p.Glu665Ter) single nucleotide variant Pathogenic rs515726137 GRCh37 Chromosome 18, 55336654: 55336654
11 ATP8B1 NM_005603.4(ATP8B1): c.625C> A (p.Pro209Thr) single nucleotide variant Pathogenic rs515726138 GRCh38 Chromosome 18, 57697797: 57697797
12 NR1H4 NM_005123.3(NR1H4): c.419_420insAAA (p.Tyr139_Asn140insLys) insertion Pathogenic rs879255644 GRCh37 Chromosome 12, 100904895: 100904896
13 NR1H4 NM_005123.3(NR1H4): c.526C> T (p.Arg176Ter) single nucleotide variant Pathogenic rs113090017 GRCh37 Chromosome 12, 100926316: 100926316
14 NR1H4 NC_000012.11: g.100886254_100917988del31735 deletion Pathogenic GRCh37 Chromosome 12, 100886254: 100917988
15 ATP8B1 NM_005603.4(ATP8B1): c.3410C> G (p.Ser1137Ter) single nucleotide variant Pathogenic rs74414989 GRCh37 Chromosome 18, 55317720: 55317720
16 ATP8B1 NM_005603.4(ATP8B1): c.279G> A (p.Ala93=) single nucleotide variant Pathogenic rs761575295 GRCh37 Chromosome 18, 55373722: 55373722

Expression for Cholestasis, Progressive Familial Intrahepatic 1

Search GEO for disease gene expression data for Cholestasis, Progressive Familial Intrahepatic 1.

Pathways for Cholestasis, Progressive Familial Intrahepatic 1

GO Terms for Cholestasis, Progressive Familial Intrahepatic 1

Cellular components related to Cholestasis, Progressive Familial Intrahepatic 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 integral component of plasma membrane GO:0005887 9.65 ABCB11 ABCB4 ATP8B1 JAG1 SLC10A2
2 apical part of cell GO:0045177 9.33 ABCB11 ABCB4 JAG1
3 brush border membrane GO:0031526 9.32 ABCB4 ATP8B1
4 intercellular canaliculus GO:0046581 8.96 ABCB11 ABCB4
5 apical plasma membrane GO:0016324 8.92 ABCB4 ATP8B1 JAG1 SLC10A2

Biological processes related to Cholestasis, Progressive Familial Intrahepatic 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.72 ABCB11 ABCB4 ATP8B1 MYO5B SLC10A2
2 phospholipid translocation GO:0045332 9.26 ABCB4 ATP8B1
3 drug transmembrane transport GO:0006855 9.16 ABCB4 ATP8B1
4 bile acid metabolic process GO:0008206 8.96 ATP8B1 NR1H4
5 bile acid and bile salt transport GO:0015721 8.92 ABCB11 ATP8B1 NR1H4 SLC10A2

Molecular functions related to Cholestasis, Progressive Familial Intrahepatic 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 ATPase activity, coupled to transmembrane movement of substances GO:0042626 8.62 ABCB11 ABCB4

Sources for Cholestasis, Progressive Familial Intrahepatic 1

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 Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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