PFIC1
MCID: CHL132
MIFTS: 57

Cholestasis, Progressive Familial Intrahepatic, 1 (PFIC1)

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

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic, 1

MalaCards integrated aliases for Cholestasis, Progressive Familial Intrahepatic, 1:

Name: Cholestasis, Progressive Familial Intrahepatic, 1 56 73
Cholestasis, Progressive Familial Intrahepatic 1 56 74 29 13 6 43
Byler Disease 56 52 58 73 54
Pfic1 56 12 52 58 73
Progressive Familial Intrahepatic Cholestasis 1 12 52 15
Fic1 Deficiency 12 58
Cholestasis, Intrahepatic, Familial, Progressive, Type 1 39
Progressive Familial Intrahepatic Cholestasis Type 1 58
Cholestasis, Progressive Familial Intrahepatic 3 71
Progressive Familial Intrahepatic Cholestasis 52
Progressive Intrahepatic Cholestasis 71
Cholestasis, Fatal Intrahepatic 52
Fatal Intrahepatic Cholestasis 73
Severe Atp8b1 Deficiency 52
Byler's Disease 52

Characteristics:

Orphanet epidemiological data:

58
progressive familial intrahepatic cholestasis type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in early infancy
genetic heterogeneity, see also pfic2 , pfic3
caused by a defect in bile acid transport
allelic disorder to benign recurrent intrahepatic cholestasis (bric1, )
allelic disorder to intrahepatic cholestasis of pregnancy (icp, )


HPO:

31
cholestasis, progressive familial intrahepatic, 1:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare hepatic diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0070226
OMIM 56 211600
OMIM Phenotypic Series 56 PS211600
MESH via Orphanet 44 C535933
ICD10 via Orphanet 33 K76.8
Orphanet 58 ORPHA79306
UMLS 71 C0268312 C1865643

Summaries for Cholestasis, Progressive Familial Intrahepatic, 1

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 79306 Definition PFIC1, a type of progressive familial intrahepathic cholestasis (PFIC, see this term), is an infantile hereditary disorder in bile formation that is hepatocellular in origin and associated with extrahepatic features. Epidemiology Estimated prevalence at birth of PFIC types 1-3 varies between 1/50,000 and 1/100,000 births. PFIC1 is the less frequent type of PFIC. Clinical description Its onset occurs mostly during infancy. Clinical signs of cholestasis (discolored stools, dark urine) usually appear in the first months of life with recurrent or permanent jaundice associated with hepatomegaly and severe pruritus. Patients usually develop fibrosis and end-stage liver disease before adulthood. Extrahepatic features have been reported including persistent short stature , watery diarrhea, pancreatitis and sensorineural deafness. Etiology PFIC1 is due to mutations in the ATP8B1 gene (18q21-22) encoding the FIC1 protein expressed at the canalicular membrane of hepatocytes as well as in other epithelia. In hepatocytes, abnormal protein might indirectly disrupt biliary bile acid secretion, explaining the low biliary bile acid concentration found in PFIC1 patients. Extrahepatic features of the disease are probably related to the extrahepatic expression of FIC1. Diagnostic methods PFIC1 should be suspected in children with a clinical history of cholestasis of unknown origin after exclusion of the other main causes of cholestasis presenting with normal serum gamma-GT activity and high serum bile acid concentration. Usually, serum alpha-fetoprotein level is normal and alanine aminotransferase values are below five times the upper limit of normal. Liver ultrasonography is usually normal but may reveal a huge gallbladder. Liver histology reveals canalicular cholestasis and the absence of true ductular proliferation with only periportal biliary metaplasia of hepatocytes. When performed, cholangiography shows a normal biliary tree and allows bile collection. Biliary lipid analysis reveals mildly decreased biliary bile salt concentration. Genotyping confirms the diagnosis. Differential diagnosis In the scope of cholestasis with normal gamma-GT, differential diagnosis includes mainly primary bile acid synthesis defects and PFIC2 (see these terms). Antenatal diagnosis Prenatal diagnosis can be proposed if a mutation has been identified in each parent. Genetic counseling Transmission is autosomal recessive . Management and treatment Ursodeoxycholic acid therapy (UDCA) should be initiated in all patients to prevent liver damage but is not fully effective. Rifampicin is helpful to control pruritus. Nasobiliary drainage may help to select potential responders to biliary diversion. However, because of severe cholestasis, half of patients are ultimately candidates for liver transplantation (LT). Diarrhea often worsens after LT and might be favorably managed by bile adsorptive resin treatment. LT does not prevent extrahepatic progression of the disease, and does not lead to catch-up growth. Furthermore, severe steatohepatitis of the liver graft has been reported. Specialized follow-up is mandatory lifelong. FIC1 defect predisposes to development of intrahepatic cholestasis of pregnancy (see this term). Visit the Orphanet disease page for more resources.

MalaCards based summary : Cholestasis, Progressive Familial Intrahepatic, 1, also known as cholestasis, progressive familial intrahepatic 1, is related to cholestasis, progressive familial intrahepatic, 4 and cholestasis, progressive familial intrahepatic, 3, and has symptoms including pruritus, diarrhea and icterus. An important gene associated with Cholestasis, Progressive Familial Intrahepatic, 1 is ATP8B1 (ATPase Phospholipid Transporting 8B1), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Cardiac conduction. The drugs Glycerol and Estrogens have been mentioned in the context of this disorder. Affiliated tissues include liver and lung, and related phenotypes are splenomegaly and hepatomegaly

Disease Ontology : 12 A progressive familial intrahepatic cholestasis characterized by autosomal recessive inheritance that has material basis in mutation in the ATP8B1 gene on chromosome 18q21.

OMIM : 56 Progressive familial intrahepatic cholestasis is a heterogeneous group of autosomal recessive liver disorders characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood (Alonso et al., 1994; Whitington et al., 1994; Klomp et al., 2004). (211600)

UniProtKB/Swiss-Prot : 73 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 : 74 Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions... more...

Related Diseases for Cholestasis, Progressive Familial Intrahepatic, 1

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, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 126)
# Related Disease Score Top Affiliating Genes
1 cholestasis, progressive familial intrahepatic, 4 33.5 TJP2 SLC10A2 NR1H4 ATP8B1 ABCC2 ABCB4
2 cholestasis, progressive familial intrahepatic, 3 32.9 TJP2 SLC10A2 SLC10A1 NR1H4 JAG1 ATP8B1
3 bile acid synthesis defect, congenital, 2 32.3 SLC10A1 NR1H4 CYP7A1 ABCB11
4 cholestasis, progressive familial intrahepatic, 5 32.0 TJP2 NR1H4 ATP8B1 ABCB4 ABCB11
5 atp8b1 deficiency 31.2 NR1H4 ATP8B1 ABCB11
6 cholestasis, progressive familial intrahepatic, 2 31.0 TJP2 SLC10A2 SLC10A1 NR1H4 CYP7A1 ATP8B1
7 alagille syndrome 1 30.9 JAG1 ATP8B1 ABCB4 ABCB11
8 cholangitis 30.8 NR1H4 GGT1 ABCB4 ABCB11
9 intrahepatic cholestasis of pregnancy 30.8 NR1H4 ATP8B1 ABCC2 ABCB4 ABCB11
10 biliary atresia, extrahepatic 30.7 JAG1 GGT1
11 cholestasis, intrahepatic, of pregnancy 3 30.6 ABCB4 ABCB11
12 hypercholesterolemia, familial, 1 30.3 NR1H4 CYP7A1 ABCG5
13 cholelithiasis 30.1 NR1H4 GGT1 CYP7A1 ABCG5 ABCB4
14 bilirubin metabolic disorder 30.1 GGT1 ATP8B1 ABCC2 ABCB4 ABCB11
15 lipid metabolism disorder 29.9 NR1H4 GGT1 CYP7A1
16 biliary atresia 29.8 SLC10A2 SLC10A1 NR1H4 JAG1 GGT1 ATP8B1
17 cholestasis, intrahepatic, of pregnancy, 1 29.8 SLC10A2 NR1H4 JAG1 GGT1 ATP8B1 ABCC2
18 primary biliary cirrhosis 29.7 SLC10A1 NR1H4 GGT1 CYP7A1 ABCC2 ABCB4
19 progressive familial intrahepatic cholestasis 29.6 TMEM30A TJP2 SLC10A2 SLC10A1 NR1H4 MYO5B
20 cholestasis, benign recurrent intrahepatic, 1 29.5 TMEM30A TJP2 SLC10A2 SLC10A1 NR1H4 CYP7A1
21 liver disease 29.5 TJP2 SLC10A1 NR1H4 GGT1 ATP8B1 ABCC2
22 familial intrahepatic cholestasis 29.4 TMEM30A TJP2 SLC10A2 NR1H4 LOC100505549 GGT1
23 cholestasis 29.2 TJP2 SLC10A2 SLC10A1 NR1H4 JAG1 GGT1
24 cholestasis, benign recurrent intrahepatic, 2 28.9 TJP2 SLC10A2 SLC10A1 NR1H4 CYP7A1 ATP8B1
25 myo5b-related progressive familial intrahepatic cholestasis 12.6
26 bile acid synthesis defect, congenital, 1 12.3
27 arthrogryposis, renal dysfunction, and cholestasis 1 11.4
28 diarrhea 10.5
29 parenteral nutrition-associated cholestasis 10.4 GGT1 ABCB4
30 perforation of bile duct 10.4 GGT1 ATP8B1
31 suppurative cholangitis 10.4 GGT1 ABCB4
32 autosomal dominant non-syndromic intellectual disability 3 10.4 ABCB4 ABCB11
33 bile duct cysts 10.3 GGT1 ATP8B1 ABCB4
34 common bile duct disease 10.3 GGT1 ABCB4
35 hypoparathyroidism, x-linked 10.3 ATP11C ATP11A
36 hepatocellular carcinoma 10.3
37 47,xyy 10.3
38 functional diarrhea 10.2 SLC10A2 NR1H4 CYP7A1
39 dubin-johnson syndrome 10.2 ATP8B1 ABCC2 ABCB11
40 pericholangitis 10.2 SLC10A2 SLC10A1 ABCB4 ABCB11
41 caroli disease 10.2 ATP8B1 ABCB4
42 rickets 10.2
43 varicose veins 10.2
44 wilson disease 10.2
45 ataxia and polyneuropathy, adult-onset 10.2
46 gallbladder disease 1 10.2
47 cholangiocarcinoma 10.2
48 intrahepatic cholangiocarcinoma 10.2
49 acute liver failure 10.2
50 rapidly involuting congenital hemangioma 10.1

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

Human phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 1:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 31 HP:0001744
2 hepatomegaly 31 HP:0002240
3 failure to thrive 31 HP:0001508
4 pruritus 31 HP:0000989
5 cirrhosis 31 HP:0001394
6 jaundice 31 HP:0000952
7 fat malabsorption 31 HP:0002630
8 severe short stature 31 HP:0003510
9 diarrhea 31 HP:0002014
10 conjugated hyperbilirubinemia 31 HP:0002908
11 intrahepatic cholestasis with episodic jaundice 31 HP:0006575

Symptoms via clinical synopsis from OMIM:

56
Abdomen Spleen:
splenomegaly

Growth Height:
short stature

Skin Nails Hair Skin:
pruritus
jaundice

Laboratory Abnormalities:
conjugated hyperbilirubinemia
normal or mildly increased serum gamma-ggt
decreased serum cholesterol
increased serum bile acids

Abdomen Liver:
hepatomegaly
cirrhosis
jaundice
intrahepatic cholestasis
intracanalicular cholestasis shown on biopsy
more
Growth Other:
failure to thrive
growth retardation

Abdomen Gastrointestinal:
diarrhea
malabsorption of fat and fat-soluble vitamins

Clinical features from OMIM:

211600

UMLS symptoms related to Cholestasis, Progressive Familial Intrahepatic, 1:


pruritus, diarrhea, icterus

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

45
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.24 ABCB11 ABCB4 ABCG5 ATP11A ATP8A1 ATP8A2
2 homeostasis/metabolism MP:0005376 10.19 ABCB11 ABCB4 ABCC2 ABCG5 ATP11A ATP11C
3 hematopoietic system MP:0005397 10.02 ABCB4 ABCC2 ABCG5 ATP11A ATP11C ATP8A1
4 digestive/alimentary MP:0005381 10.01 ABCB4 ABCG5 ATP8A2 CYP7A1 JAG1 MYO5B
5 liver/biliary system MP:0005370 9.9 ABCB11 ABCB4 ABCC2 ABCG5 ATP11A ATP8B1
6 mortality/aging MP:0010768 9.77 ABCB11 ABCG5 ATP11A ATP8A2 ATP8B1 ATP8B2
7 vision/eye MP:0005391 9.23 ABCB11 ATP11A ATP8A2 ATP8B1 CYP7A1 GGT1

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 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Glycerol Approved, Investigational 56-81-5 753
2 Estrogens
3 4-phenylbutyric acid
4 Protective Agents
5 Liver Extracts
6 Bile Acids and Salts
7 Alpha 1-Antitrypsin
8 Protein C Inhibitor

Interventional clinical trials:

(show all 17)
# Name Status NCT ID Phase Drugs
1 An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 2) Recruiting NCT03659916 Phase 3 A4250 (odevixibat)
2 MRX-502: Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Maralixibat in the Treatment of Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC) - MARCH-PFIC Recruiting NCT03905330 Phase 3 Maralixibat
3 A Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study to Demonstrate Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 1) Active, not recruiting NCT03566238 Phase 3 A4250 (odevixibat);Placebo
4 An Open-label Extension Study to Evaluate the Long-term Safety and Efficacy of Maralixibat in the Treatment of Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC) Enrolling by invitation NCT04185363 Phase 3 Maralixibat
5 Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Maralixibat (SHP625) in the Treatment of Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC) Withdrawn NCT03353454 Phase 3 Maralixibat;Placebo
6 Open Label Study of the Efficacy and Long Term Safety of LUM001, an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Pediatric Patients With Progressive Familial Intrahepatic Cholestasis Completed NCT02057718 Phase 2 LUM001
7 MRX-800: A Long-Term Safety Study of Maralixibat, an Apical Sodium Dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Subjects Who Previously Participated in a Maralixibat Study Enrolling by invitation NCT04168385 Phase 2 Maralixibat
8 Efficacy and Tolerance of RADIOEMBOLIZATION for Patients With Unresectable Intrahepatic Cholangiocarcinoma With Tumor Progression After First-line Therapy Terminated NCT01383746 Phase 1, Phase 2
9 Mutations and Polymorphisms of Gene ABCB4 Among Women Suffering From Intrahepatic Cholestasis of Pregnancy. A Study With a Control Group. Completed NCT00700232
10 Sulfation of Bile Acids as a Biomarker for Hepatobiliary Diseases Recruiting NCT01200082
11 NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion (NAPPED Study), Meta-analysis of Individual Patient Data of PFIC Before and After Surgery (Bile Diversion or Liver Transplantation) Enrolling by invitation NCT03930810
12 Gastrostomy-Biliary Diversion: Innovative Management for Children With Bile Canalicular Transport Disorders Not yet recruiting NCT04071197
13 Compassionate Use of Buphenyl® in the Treatment of Byler's Disease No longer available NCT01784718 Buphenyl
14 Transition From Buphenyl to RAVICTI for the Therapy of Byler Disease No longer available NCT01949766 Glycerol phenylbutyrate
15 Expanded Access Protocol for an Intermediate Size Population - RAVICTI for Byler Disease No longer available NCT02094222 RAVICTI
16 Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC) Suspended NCT00571272
17 Longitudinal Study of Mitochondrial Hepatopathies Suspended NCT01148550

Search NIH Clinical Center for Cholestasis, Progressive Familial Intrahepatic, 1

Cochrane evidence based reviews: cholestasis, progressive familial intrahepatic 1

Genetic Tests for Cholestasis, Progressive Familial Intrahepatic, 1

Genetic tests related to Cholestasis, Progressive Familial Intrahepatic, 1:

# Genetic test Affiliating Genes
1 Cholestasis, Progressive Familial Intrahepatic 1 29 ATP8B1

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic, 1

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

40
Liver, Lung

Publications for Cholestasis, Progressive Familial Intrahepatic, 1

Articles related to Cholestasis, Progressive Familial Intrahepatic, 1:

(show top 50) (show all 101)
# Title Authors PMID Year
1
A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. 6 56 61
9500542 1998
2
Characterization of mutations in ATP8B1 associated with hereditary cholestasis. 6 56
15239083 2004
3
A missense mutation in FIC1 is associated with greenland familial cholestasis. 6 56
11093741 2000
4
Byler disease. Fatal familial intrahepatic cholestasis in an Amish kindred. 6 56
5762004 1969
5
Mutations in TJP2 cause progressive cholestatic liver disease. 56
24614073 2014
6
Dynamic regulation of cardiolipin by the lipid pump Atp8b1 determines the severity of lung injury in experimental pneumonia. 6
20852622 2010
7
Reduced hepatic expression of farnesoid X receptor in hereditary cholestasis associated to mutation in ATP8B1. 6
15317749 2004
8
Resistance to parathyroid hormone in two patients with familial intrahepatic cholestasis: possible involvement of the ATP8B1 gene in calcium regulation via parathyroid hormone. 56
15448432 2004
9
ATP8B1 Deficiency 6
20301474 2001
10
Linkage of Cholestasis Familiaris Groenlandica/Byler-like disease to chromosome 18. 56
10850008 2000
11
Recurrent familial intrahepatic cholestasis in the Faeroe Islands. Phenotypic heterogeneity but genetic homogeneity. 6
9918928 1999
12
Sensorineural hearing loss associated with Byler disease. 56
10458497 1999
13
Molecular pathogenesis of cholestasis. 56
9780343 1998
14
Progressive familial intrahepatic cholestasis (PFIC): evidence for genetic heterogeneity by exclusion of linkage to chromosome 18q21-q22. 56
9272158 1997
15
Mapping of a locus for progressive familial intrahepatic cholestasis (Byler disease) to 18q21-q22, the benign recurrent intrahepatic cholestasis region. 56
7655458 1995
16
Evidence for defective primary bile acid secretion in children with progressive familial intrahepatic cholestasis (Byler disease). 56
8088298 1994
17
Histologic pathology of the liver in progressive familial intrahepatic cholestasis. 56
8014759 1994
18
Clinical and biochemical findings in progressive familial intrahepatic cholestasis. 56
7912266 1994
19
Linkage studies of cholestasis familiaris groenlandica/Byler-like disease with polymorphic protein and blood group markers. 56
8344670 1993
20
Diagnostic value of serum gamma-glutamyl transpeptidase activity in liver diseases in children. 56
1676410 1991
21
Normal serum gamma-glutamyl-transpeptidase activity identifies groups of infants with idiopathic cholestasis with poor prognosis. 56
2886574 1987
22
Fatal familial cholestatic syndrome in Greenland Eskimo children. 56
3564958 1986
23
Improved neurologic function after long-term correction of vitamin E deficiency in children with chronic cholestasis. 56
4069170 1985
24
Neuropathology of chronic vitamine E deficiency in fatal familial intrahepatic cholestasis. 56
7158298 1982
25
Familial cholestasis with elevated sweat electrolyte concentrations. 56
7277100 1981
26
Hepatoma in siblings with progressive familial cholestatic cirrhosis of childhood. 56
6267930 1981
27
Familial cholestatic cirrhosis associated with Kayser-Fleischer rings. 56
7367085 1980
28
A study of inheritance in progressive intrahepatic cholestasis: hepatic excretory function in unaffected family members. 56
503649 1979
29
Efficacy and safety of long-term phenobarbital therapy of familial cholestasis. 56
650323 1978
30
Progressive intrahepatic cholestasis of infancy and childhood. A clinicopathological study of patient surviving to the age of 18 years. 56
955355 1976
31
Progressive intrahepatic cholestasis (Byler's disease): case report. 56
1218817 1975
32
Progressive familial intrahepatic cholestasis. 56
4710460 1973
33
Byler's disease: fatal intrahepatic cholestasis. 56
5049817 1972
34
Progressive familial cholestatic cirrhosis and bile acid metabolism. 56
5049818 1972
35
Intermittent intrahepatic cholestasis of unknown etiology in five young males from the Faroe Islands. 6
5807632 1969
36
A case of familial intrahepatic cholestasis. 56
4175258 1968
37
Familial intrahepatic cholestasis with mental and growth retardation. 56
5954222 1966
38
Familial intrahepatic cholestatic jaundice in infancy. 56
5940621 1966
39
[Familial jaundice caused by intrahepatic cholestasis]. 56
5998368 1966
40
DHPLC screening for mutations in progressive familial intrahepatic cholestasis patients. 61 54
20414253 2010
41
Folding defects in P-type ATP 8B1 associated with hereditary cholestasis are ameliorated by 4-phenylbutyrate. 54 61
19918981 2010
42
[Genetic cholestasis]. 61 54
19753442 2009
43
ATP8B1 deficiency disrupts the bile canalicular membrane bilayer structure in hepatocytes, but FXR expression and activity are maintained. 61 54
19027009 2009
44
FIC1-mediated stimulation of FXR activity is decreased with PFIC1 mutations in HepG2 cells. 61 54
19381753 2009
45
Progressive familial intrahepatic cholestasis. 61 54
19133130 2009
46
Novel resequencing chip customized to diagnose mutations in patients with inherited syndromes of intrahepatic cholestasis. 61 54
17241866 2007
47
Normal pancreatic secretion in children with progressive familial intrahepatic cholestasis type 1. 54 61
17101580 2006
48
Bile salt excretory pump: biology and pathobiology. 61 54
16819395 2006
49
Altered hepatobiliary gene expressions in PFIC1: ATP8B1 gene defect is associated with CFTR downregulation. 61 54
16628629 2006
50
ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy. 54 61
15888793 2005

Variations for Cholestasis, Progressive Familial Intrahepatic, 1

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

6 (show top 50) (show all 179) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ABCB4 NM_000443.4(ABCB4):c.1553del (p.Leu518fs)deletion Pathogenic 595241 rs1562976061 7:87069522-87069522 7:87440206-87440206
2 ABCB4 NM_000443.4(ABCB4):c.475C>T (p.Arg159Ter)SNV Pathogenic 596680 rs377160065 7:87082321-87082321 7:87453005-87453005
3 ABCB4 NM_000443.4(ABCB4):c.1745G>A (p.Arg582Gln)SNV Pathogenic 802327 7:87060868-87060868 7:87431552-87431552
4 ABCB4 NM_000443.4(ABCB4):c.1714C>T (p.Gln572Ter)SNV Pathogenic 802328 7:87069000-87069000 7:87439684-87439684
5 ATP8B1 NM_005603.6(ATP8B1):c.923G>T (p.Gly308Val)SNV Pathogenic 7262 rs111033609 18:55362420-55362420 18:57695188-57695188
6 ATP8B1 NM_005603.6(ATP8B1):c.2674G>A (p.Gly892Arg)SNV Pathogenic 7263 rs121909098 18:55328439-55328439 18:57661207-57661207
7 ATP8B1 NM_005603.6(ATP8B1):c.863T>C (p.Leu288Ser)SNV Pathogenic 7264 rs121909099 18:55362480-55362480 18:57695248-57695248
8 ATP8B1 NM_005603.6(ATP8B1):c.2097+2T>CSNV Pathogenic 7265 rs387906381 18:55336548-55336548 18:57669316-57669316
9 ATP8B1 ATP8B1, 1.4-KB DELdeletion Pathogenic 7266
10 ATP8B1 NM_005603.6(ATP8B1):c.1660G>A (p.Asp554Asn)SNV Pathogenic 7269 rs121909101 18:55342225-55342225 18:57674993-57674993
11 ATP8B1 NM_005603.6(ATP8B1):c.1993G>T (p.Glu665Ter)SNV Pathogenic 126382 rs515726137 18:55336654-55336654 18:57669422-57669422
12 ATP8B1 NM_005603.6(ATP8B1):c.625C>A (p.Pro209Thr)SNV Pathogenic 126383 rs515726138 18:55365029-55365029 18:57697797-57697797
13 ATP8B1 NM_005603.6(ATP8B1):c.1367C>T (p.Thr456Met)SNV Pathogenic 7273 rs121909104 18:55355593-55355593 18:57688361-57688361
14 ATP8B1 NM_005603.6(ATP8B1):c.1804C>T (p.Arg602Ter)SNV Pathogenic 7274 rs121909105 18:55342081-55342081 18:57674849-57674849
15 NR1H4 deletion Pathogenic 219163 12:100886254-100917988 12:100492476-100524210
16 NR1H4 NM_001206979.2(NR1H4):c.419_420insAAA (p.Asn140_Ala141insLys)insertion Pathogenic 219162 rs879255644 12:100904893-100904894 12:100511115-100511116
17 NR1H4 NM_001206979.2(NR1H4):c.526C>T (p.Arg176Ter)SNV Pathogenic 219164 rs113090017 12:100926316-100926316 12:100532538-100532538
18 ABCB4 NM_000443.4(ABCB4):c.3724dup (p.Ile1242fs)duplication Pathogenic/Likely pathogenic 594504 rs1562945221 7:87031527-87031528 7:87402211-87402212
19 ABCB4 NM_000443.4(ABCB4):c.2784-12T>CSNV Likely pathogenic 802326 7:87041361-87041361 7:87412045-87412045
20 ABCB4 NM_000443.4(ABCB4):c.1210C>G (p.Pro404Ala)SNV Likely pathogenic 242455 rs863225298 7:87072999-87072999 7:87443683-87443683
21 ABCB4 NM_000443.4(ABCB4):c.1322T>G (p.Leu441Arg)SNV Likely pathogenic 802329 7:87072669-87072669 7:87443353-87443353
22 ABCB4 NM_000443.4(ABCB4):c.1119+5G>ASNV Likely pathogenic 802330 7:87074173-87074173 7:87444857-87444857
23 ATP8B1 NM_001374385.1(ATP8B1):c.3394T>G (p.Phe1132Val)SNV Likely pathogenic 803502 18:55319272-55319272 18:57652040-57652040
24 ATP8B1 NM_001374385.1(ATP8B1):c.3015+1G>TSNV Likely pathogenic 803503 18:55321223-55321223 18:57653991-57653991
25 ATP8B1 NM_001374385.1(ATP8B1):c.173del (p.Phe58fs)deletion Likely pathogenic 803504 18:55398867-55398867 18:57731635-57731635
26 ATP8B1 , LOC100505549 NM_001374385.1(ATP8B1):c.2251G>T (p.Glu751Ter)SNV Likely pathogenic 804427 18:55334358-55334358 18:57667126-57667126
27 ABCB4 NM_000443.4(ABCB4):c.2217T>G (p.Phe739Leu)SNV Conflicting interpretations of pathogenicity 593160 rs143456575 7:87051536-87051536 7:87422220-87422220
28 ATP8B1 NM_005603.6(ATP8B1):c.208G>A (p.Asp70Asn)SNV Conflicting interpretations of pathogenicity 7271 rs34719006 18:55373793-55373793 18:57706561-57706561
29 ATP8B1 NM_005603.6(ATP8B1):c.1982T>C (p.Ile661Thr)SNV Conflicting interpretations of pathogenicity 7267 rs121909100 18:55336665-55336665 18:57669433-57669433
30 ABCB4 NM_000443.4(ABCB4):c.1769G>A (p.Arg590Gln)SNV Conflicting interpretations of pathogenicity 13697 rs45575636 7:87060844-87060844 7:87431528-87431528
31 ABCB4 NM_000443.4(ABCB4):c.101C>T (p.Thr34Met)SNV Conflicting interpretations of pathogenicity 196273 rs142794414 7:87101971-87101971 7:87472655-87472655
32 ATP8B1 NM_005603.6(ATP8B1):c.150A>G (p.Glu50=)SNV Conflicting interpretations of pathogenicity 195247 rs137973298 18:55398890-55398890 18:57731658-57731658
33 ABCB4 NM_000443.4(ABCB4):c.2800G>A (p.Ala934Thr)SNV Conflicting interpretations of pathogenicity 281139 rs61730509 7:87041333-87041333 7:87412017-87412017
34 ATP8B1 NM_005603.6(ATP8B1):c.913T>A (p.Phe305Ile)SNV Conflicting interpretations of pathogenicity 289557 rs150860808 18:55362430-55362430 18:57695198-57695198
35 ATP8B1 NM_005603.6(ATP8B1):c.134A>C (p.Asn45Thr)SNV Conflicting interpretations of pathogenicity 290971 rs146599962 18:55398906-55398906 18:57731674-57731674
36 ABCB4 NM_000443.4(ABCB4):c.1529A>G (p.Asn510Ser)SNV Conflicting interpretations of pathogenicity 291252 rs375315619 7:87069546-87069546 7:87440230-87440230
37 ATP8B1 NM_005603.6(ATP8B1):c.1072G>A (p.Gly358Ser)SNV Conflicting interpretations of pathogenicity 327489 rs193204986 18:55359187-55359187 18:57691955-57691955
38 ATP8B1 NM_005603.6(ATP8B1):c.-48C>TSNV Conflicting interpretations of pathogenicity 327498 rs150844949 18:55470255-55470255 18:57803023-57803023
39 ATP8B1 NM_005603.6(ATP8B1):c.1711G>A (p.Ala571Thr)SNV Conflicting interpretations of pathogenicity 327485 rs35140429 18:55342174-55342174 18:57674942-57674942
40 ATP8B1 NM_005603.6(ATP8B1):c.2988C>T (p.Pro996=)SNV Conflicting interpretations of pathogenicity 327471 rs776385207 18:55321251-55321251 18:57654019-57654019
41 ATP8B1 NM_005603.6(ATP8B1):c.3696G>A (p.Ser1232=)SNV Conflicting interpretations of pathogenicity 327466 rs754912569 18:55315780-55315780 18:57648548-57648548
42 ABCB4 NM_000443.4(ABCB4):c.2144C>T (p.Thr715Ile)SNV Conflicting interpretations of pathogenicity 381720 rs138773456 7:87053289-87053289 7:87423973-87423973
43 ATP8B1 NM_005603.6(ATP8B1):c.1014C>T (p.Asn338=)SNV Conflicting interpretations of pathogenicity 386015 rs145750280 18:55361829-55361829 18:57694597-57694597
44 ATP8B1 NM_005603.6(ATP8B1):c.1286A>C (p.Glu429Ala)SNV Conflicting interpretations of pathogenicity 381740 rs34018205 18:55355674-55355674 18:57688442-57688442
45 ATP8B1 NM_005603.6(ATP8B1):c.2546G>A (p.Arg849Gln)SNV Uncertain significance 383293 rs144656719 18:55328567-55328567 18:57661335-57661335
46 ATP8B1 NM_005603.6(ATP8B1):c.3481G>A (p.Val1161Ile)SNV Uncertain significance 327468 rs771155047 18:55317649-55317649 18:57650417-57650417
47 ATP8B1 NM_005603.6(ATP8B1):c.2939A>G (p.Tyr980Cys)SNV Uncertain significance 327473 rs886054010 18:55321300-55321300 18:57654068-57654068
48 ATP8B1 NM_005603.6(ATP8B1):c.1681G>A (p.Ala561Thr)SNV Uncertain significance 327486 rs372806297 18:55342204-55342204 18:57674972-57674972
49 ATP8B1 NM_005603.6(ATP8B1):c.-62C>TSNV Uncertain significance 327499 rs886054016 18:55470269-55470269 18:57803037-57803037
50 ATP8B1 NM_005603.6(ATP8B1):c.*776G>ASNV Uncertain significance 327452 rs886054003 18:55314944-55314944 18:57647712-57647712

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

73 (show all 17)
# Symbol AA change Variation ID SNP ID
1 ATP8B1 p.Leu288Ser VAR_008809 rs121909099
2 ATP8B1 p.Gly308Val VAR_008810 rs111033609
3 ATP8B1 p.Ile661Thr VAR_008812 rs121909100
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 rs133797849
13 ATP8B1 p.Gly733Arg VAR_043069 rs135036936
14 ATP8B1 p.Phe853Ser VAR_043071 rs773092889
15 ATP8B1 p.Gly1040Arg VAR_043073 rs143824965
16 ATP8B1 p.Pro209Thr VAR_071045 rs515726138
17 ATP8B1 p.Ser1012Ile VAR_071046

Cosmic variations for Cholestasis, Progressive Familial Intrahepatic, 1:

9
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM134614922 biliary tract,gallbladder,other,metaplasia c.35G>A p.G12D 12:25245350-25245350 0

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

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.15 MYO5B ATP8B2 ATP8B1 ATP8A2 ATP8A1 ATP11C
2
Show member pathways
12.64 ATP8B2 ATP8B1 ATP8A2 ATP8A1 ATP11C ATP11A
3
Show member pathways
12.34 ATP8B2 ATP8B1 ATP8A2 ATP8A1 ATP11C ATP11A
4
Show member pathways
12.05 SLC10A2 SLC10A1 NR1H4 CYP7A1 ABCB11
5
Show member pathways
11.85 SLC10A1 ABCC2 ABCB4 ABCB11
6
Show member pathways
11.73 CYP7A1 ABCG5 ABCB11
7 11.18 SLC10A2 SLC10A1 NR1H4 CYP7A1 ABCG5 ABCC2
8 10.98 NR1H4 CYP7A1 ABCG5 ABCC2 ABCB4 ABCB11
9 10.93 SLC10A1 NR1H4 CYP7A1 ABCB4 ABCB11
10 10.78 SLC10A1 NR1H4 CYP7A1 ABCC2 ABCB11

GO Terms for Cholestasis, Progressive Familial Intrahepatic, 1

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.3 TMEM30A TJP2 SLC10A2 SLC10A1 JAG1 GGT1
2 integral component of membrane GO:0016021 10.22 TMEM30A SLC10A2 SLC10A1 JAG1 GGT1 CYP7A1
3 plasma membrane GO:0005886 10.06 TMEM30A TJP2 SLC10A2 SLC10A1 JAG1 GGT1
4 endoplasmic reticulum GO:0005783 10.02 TMEM30A CYP7A1 ATP8B2 ATP8B1 ATP8A1 ATP11C
5 integral component of plasma membrane GO:0005887 10.01 SLC10A2 SLC10A1 JAG1 ATP8B1 ABCG5 ABCC2
6 recycling endosome GO:0055037 9.67 MYO5B ATP11C ATP11A
7 apical part of cell GO:0045177 9.63 JAG1 ABCG5 ABCB11
8 specific granule membrane GO:0035579 9.61 TMEM30A ATP8A1 ATP11A
9 apical plasma membrane GO:0016324 9.5 TMEM30A SLC10A2 JAG1 ATP8B1 ABCG5 ABCC2
10 intercellular canaliculus GO:0046581 9.43 ABCC2 ABCB4 ABCB11
11 trans-Golgi network GO:0005802 9.1 ATP8B2 ATP8B1 ATP8A2 ATP8A1 ATP11C ATP11A

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

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.91 SLC10A2 SLC10A1 ATP8A1 ABCG5 ABCC2 ABCB4
2 ion transmembrane transport GO:0034220 9.84 ATP8B2 ATP8B1 ATP8A1 ATP11C
3 bile acid and bile salt transport GO:0015721 9.73 SLC10A2 SLC10A1 NR1H4 ATP8B1 ABCC2 ABCB11
4 cholesterol homeostasis GO:0042632 9.7 NR1H4 CYP7A1 ABCG5
5 phospholipid transport GO:0015914 9.7 TMEM30A ATP8B2 ATP8B1 ATP8A2 ATP8A1 ATP11C
6 lipid transport GO:0006869 9.61 TMEM30A ATP8B2 ATP8B1 ATP8A2 ATP8A1 ATP11C
7 bile acid biosynthetic process GO:0006699 9.55 CYP7A1 ABCB11
8 bile acid metabolic process GO:0008206 9.51 NR1H4 ATP8B1
9 positive regulation of phospholipid translocation GO:0061092 9.5 ATP8A2 ATP8A1 ABCB4
10 cellular response to bile acid GO:1903413 9.49 NR1H4 ABCB4
11 regulation of bile acid biosynthetic process GO:0070857 9.48 NR1H4 CYP7A1
12 aminophospholipid transport GO:0015917 9.46 TMEM30A ATP8B1
13 drug transmembrane transport GO:0006855 9.43 TMEM30A ATP8B1
14 canalicular bile acid transport GO:0015722 9.4 ABCC2 ABCB11
15 phospholipid translocation GO:0045332 9.23 TMEM30A ATP8B2 ATP8B1 ATP8A2 ATP8A1 ATP11C

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

# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 10 MYO5B ATP8B2 ATP8B1 ATP8A2 ATP8A1 ATP11C
2 ATPase activity GO:0016887 9.77 ATP8A1 ABCG5 ABCC2 ABCB4 ABCB11
3 magnesium ion binding GO:0000287 9.63 ATP8B2 ATP8B1 ATP8A2 ATP8A1 ATP11C ATP11A
4 ATPase activity, coupled to transmembrane movement of substances GO:0042626 9.62 ABCG5 ABCC2 ABCB4 ABCB11
5 bile acid:sodium symporter activity GO:0008508 9.4 SLC10A2 SLC10A1
6 ATP binding GO:0005524 9.36 MYO5B ATP8B2 ATP8B1 ATP8A2 ATP8A1 ATP11C
7 aminophospholipid transmembrane transporter activity GO:0015247 9.13 TMEM30A ATP8B1 ATP8A2

Sources for Cholestasis, Progressive Familial Intrahepatic, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....