PFIC1
MCID: CHL132
MIFTS: 53

Cholestasis, Progressive Familial Intrahepatic, 1 (PFIC1)

Categories: Cancer diseases, Endocrine 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 57 75
Byler Disease 57 53 59 75 55
Pfic1 57 12 53 59 75
Cholestasis, Progressive Familial Intrahepatic 1 57 76 13 44
Progressive Familial Intrahepatic Cholestasis 1 12 53 15
Fic1 Deficiency 12 59
Cholestasis, Intrahepatic, Familial, Progressive, Type 1 40
Progressive Familial Intrahepatic Cholestasis Type 1 59
Cholestasis, Progressive Familial Intrahepatic 3 73
Progressive Familial Intrahepatic Cholestasis 53
Progressive Intrahepatic Cholestasis 73
Cholestasis, Fatal Intrahepatic 53
Fatal Intrahepatic Cholestasis 75
Severe Atp8b1 Deficiency 53
Byler's Disease 53

Characteristics:

Orphanet epidemiological data:

59
progressive familial intrahepatic cholestasis type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
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:

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


Classifications:



External Ids:

OMIM 57 211600
Disease Ontology 12 DOID:0070226
Orphanet 59 ORPHA79306
ICD10 via Orphanet 34 K76.8
MESH via Orphanet 45 C535933
MedGen 42 C0268312

Summaries for Cholestasis, Progressive Familial Intrahepatic, 1

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79306Disease definitionPFIC1, 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.EpidemiologyEstimated 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 descriptionIts 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.EtiologyPFIC1 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 methodsPFIC1 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 diagnosisIn the scope of cholestasis with normal gamma-GT, differential diagnosis includes mainly primary bile acid synthesis defects and PFIC2 (see these terms).Antenatal diagnosisPrenatal diagnosis can be proposed if a mutation has been identified in each parent.Genetic counselingTransmission is autosomal recessive.Management and treatmentUrsodeoxycholic 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 byler disease, 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 Synthesis of bile acids and bile salts. The drugs Pharmaceutical Solutions and Liver Extracts have been mentioned in the context of this disorder. Affiliated tissues include liver, bone and pancreas, and related phenotypes are failure to thrive and splenomegaly

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 : 57 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 : 75 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 : 76 Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions... more...

Related Diseases for Cholestasis, Progressive Familial Intrahepatic, 1

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

(show all 43)
# Related Disease Score Top Affiliating Genes
1 cholestasis, progressive familial intrahepatic, 4 33.3 ABCB11 ABCB4 ATP8B1
2 cholestasis, progressive familial intrahepatic, 3 33.0 ABCB11 ABCB4 ABCG8 ATP11C ATP8B1 JAG1
3 cholestasis, progressive familial intrahepatic, 2 32.8 ABCB11 ABCB4 ABCG5 ATP8B1 NR0B2 NR1H4
4 atp8b1 deficiency 31.8 ABCB11 ATP8B1 NR1H4
5 cholestasis, progressive familial intrahepatic, 5 31.5 NR0B2 NR1H4
6 liver disease 30.2 ABCB11 ABCB4 ATP8B1 NR1H4
7 alagille syndrome 1 30.2 ABCB11 ABCB4 ATP8B1 JAG1
8 progressive familial intrahepatic cholestasis 29.8 ABCB11 ABCB4 ATP8B1 NR1H4 SLC10A2
9 cholelithiasis 29.6 ABCB4 ABCG5 ABCG8 NR1H4
10 intrahepatic cholestasis of pregnancy 29.2 ABCB11 ABCB4 ATP8B1 JAG1 NR0B2 NR1H4
11 cholestasis 29.1 ABCB11 ABCB4 ATP8B1 JAG1 NR0B2 NR1H4
12 cholestasis, benign recurrent intrahepatic, 1 29.0 ABCB11 ABCG5 ABCG8 ATP11C ATP8B1 SLC10A2
13 myo5b-related progressive familial intrahepatic cholestasis 12.4
14 bile acid synthesis defect, congenital, 1 11.9
15 arthrogryposis, renal dysfunction, and cholestasis 1 11.3
16 bile acid synthesis defect, congenital, 2 11.3
17 wilson disease 10.2
18 liver cirrhosis 10.2
19 cholestasis, benign recurrent intrahepatic, 2 10.1 ABCB11 ATP8B1
20 hepatocellular carcinoma 10.0
21 cholangiocarcinoma 10.0
22 dilated cardiomyopathy 10.0
23 pancreas adenocarcinoma 10.0
24 bone disease 10.0
25 diarrhea 10.0
26 adenocarcinoma 10.0
27 hepatoblastoma 10.0
28 sclerosing cholangitis 10.0 ABCB11 ABCB4 NR1H4
29 amyloidosis 10.0
30 al amyloidosis 10.0
31 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 9.9
32 sensorineural hearing loss 9.9
33 osteomalacia 9.9
34 cholecystitis 9.9
35 gallbladder disease 4 9.9 ABCG5 ABCG8
36 homozygous familial hypercholesterolemia 9.9 ABCG5 ABCG8
37 biliary atresia 9.9 ATP8B1 JAG1 NR1H4 SLC10A2
38 aortic atherosclerosis 9.8 ABCG5 ABCG8
39 gallbladder disease 9.8 ABCB4 ABCG5 ABCG8
40 biliary tract disease 9.8 ABCB11 ABCB4 ATP8B1 NR1H4 SLC10A2
41 sitosterolemia 9.8 ABCG5 ABCG8
42 hypercholesterolemia, familial 9.7 ABCG5 ABCG8 NR1H4 SLC10A2
43 bile duct disease 9.5 ABCB11 ABCB4 ATP8B1 NR0B2 NR1H4 SLC10A2

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 via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive
growth retardation

Abdomen Liver:
hepatomegaly
cirrhosis
jaundice
intrahepatic cholestasis
intracanalicular cholestasis shown on biopsy
more
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 Spleen:
splenomegaly

Growth Height:
short stature

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


Clinical features from OMIM:

211600

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

32 (show all 11)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 splenomegaly 32 HP:0001744
3 hepatomegaly 32 HP:0002240
4 pruritus 32 HP:0000989
5 cirrhosis 32 HP:0001394
6 jaundice 32 HP:0000952
7 diarrhea 32 HP:0002014
8 severe short stature 32 HP:0003510
9 conjugated hyperbilirubinemia 32 HP:0002908
10 fat malabsorption 32 HP:0002630
11 intrahepatic cholestasis with episodic jaundice 32 HP:0006575

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


pruritus, diarrhea, icterus

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

26
# 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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.86 ABCB4 ABCG5 ABCG8 JAG1 MYO5B NR0B2
2 growth/size/body region MP:0005378 9.81 ABCB11 ABCB4 ABCG5 ATP8B1 JAG1 MYO5B
3 homeostasis/metabolism MP:0005376 9.7 ABCB11 ABCB4 ABCG5 ABCG8 ATP11C ATP8B1
4 liver/biliary system MP:0005370 9.28 ABCB11 ABCB4 ABCG5 ABCG8 ATP8B1 JAG1

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 21)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Pharmaceutical Solutions Phase 3
2 Liver Extracts Phase 2
3 Bile Acids and Salts Phase 2
4 Cholestyramine Resin Phase 1
5 Cola Phase 1
6 Anticholesteremic Agents Phase 1
7 Lipid Regulating Agents Phase 1
8 Antimetabolites Phase 1
9 Hypolipidemic Agents Phase 1
10
Pancrelipase Approved, Investigational 53608-75-6
11
Iron Approved 7439-89-6 23925
12
Glycerol Approved, Investigational 56-81-5 753
13 Estrogens
14 Protein C Inhibitor
15 Alpha 1-Antitrypsin
16 pancreatin
17 Gastrointestinal Agents
18 Hematinics
19
Bilirubin 635-65-4 5280352
20 4-phenylbutyric acid
21 Protective Agents

Interventional clinical trials:

(show all 15)
# Name Status NCT ID Phase Drugs
1 This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC 1 or 2 Recruiting NCT03566238 Phase 3 A4250;Placebo
2 Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC Types 1 & 2 Enrolling by invitation NCT03659916 Phase 3 A4250
3 Efficacy and Safety of Maralixibat (SHP625) in the Treatment of Participants With Progressive Familial Intrahepatic Cholestasis (PFIC) Not yet recruiting NCT03353454 Phase 3 Maralixibat;Placebo
4 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 LUM001
5 An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects Completed NCT03082937 Phase 1 3 mg [14C]-A4250 capsule
6 A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384 Completed NCT02963077 Phase 1 A4250;CRC (A3384);Questran;Placebo
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 Shear Wave Sonoelastography in Pediatric Liver Fibrosis Completed NCT02372682
10 Evaluating the Genetic Causes and Progression of Cholestatic Liver Diseases (LOGIC) Recruiting NCT00571272
11 Sulfation of Bile Acids as a Biomarker for Hepatobiliary Diseases Recruiting NCT01200082
12 China Registry for Genetic / Metabolic Liver Diseases Recruiting NCT03131427 Standard of care
13 Buphenyl Therapy for 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 Temporarily not available NCT02094222 RAVICTI

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

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic, 1

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

41
Liver, Bone, Pancreas

Publications for Cholestasis, Progressive Familial Intrahepatic, 1

Articles related to Cholestasis, Progressive Familial Intrahepatic, 1:

(show all 16)
# Title Authors Year
1
Multiple Looser zones of osteomalacia in Byler disease with associated vitamin D deficiency, phosphaturia, and elevated FGF23. ( 26771453 )
2016
2
Possible Phenylacetate Hepatotoxicity During 4-Phenylbutyrate Therapy of Byler Disease. ( 26756876 )
2016
3
Byler disease: early natural history. ( 25825852 )
2015
4
Byler disease associated with acute cholecystitis. ( 11972230 )
2002
5
[Progressive familial intrahepatic cholestasis (Byler disease): current genetics and therapy]. ( 10812555 )
2000
6
Living related liver transplantation in two Byler disease families. ( 11120125 )
2000
7
Sensorineural hearing loss associated with Byler disease. ( 10458497 )
1999
8
Ursodeoxycholic acid treatment in children with Byler disease. ( 10618887 )
1999
9
Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): evidence for heterogeneity. ( 9214465 )
1997
10
Mapping of a locus for progressive familial intrahepatic cholestasis (Byler disease) to 18q21-q22, the benign recurrent intrahepatic cholestasis region. ( 7655458 )
1995
11
Evidence for defective primary bile acid secretion in children with progressive familial intrahepatic cholestasis (Byler disease). ( 8088298 )
1994
12
Hepatoma complicating Byler disease. ( 1321560 )
1992
13
Orthotopic liver transplantation for Byler disease. ( 2238055 )
1990
14
Pathology of chronic vitamin E deficiency in fatal familial intrahepatic cholestasis (Byler disease). ( 7135826 )
1982
15
Fatal familial intrahepatic cholestasis (Byler disease). ( 607765 )
1977
16
Byler disease. Fatal familial intrahepatic cholestasis in an Amish kindred. ( 5762004 )
1969

Variations for Cholestasis, Progressive Familial Intrahepatic, 1

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

75 (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

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

6 (show top 50) (show all 86)
# Gene Variation Type Significance SNP ID Assembly Location
1 ATP8B1 NM_005603.5(ATP8B1): c.923G> T (p.Gly308Val) single nucleotide variant Pathogenic rs111033609 GRCh37 Chromosome 18, 55362420: 55362420
2 ATP8B1 NM_005603.5(ATP8B1): c.923G> T (p.Gly308Val) single nucleotide variant Pathogenic rs111033609 GRCh38 Chromosome 18, 57695188: 57695188
3 ATP8B1 NM_005603.4(ATP8B1): c.2674G> A (p.Gly892Arg) single nucleotide variant Pathogenic rs121909098 GRCh37 Chromosome 18, 55328439: 55328439
4 ATP8B1 NM_005603.4(ATP8B1): c.2674G> A (p.Gly892Arg) single nucleotide variant Pathogenic rs121909098 GRCh38 Chromosome 18, 57661207: 57661207
5 ATP8B1 NM_005603.5(ATP8B1): c.863T> C (p.Leu288Ser) single nucleotide variant Pathogenic rs121909099 GRCh37 Chromosome 18, 55362480: 55362480
6 ATP8B1 NM_005603.5(ATP8B1): c.863T> C (p.Leu288Ser) single nucleotide variant Pathogenic rs121909099 GRCh38 Chromosome 18, 57695248: 57695248
7 ATP8B1 NM_005603.4(ATP8B1): c.2097+2T> C single nucleotide variant Pathogenic rs387906381 GRCh37 Chromosome 18, 55336548: 55336548
8 ATP8B1 NM_005603.4(ATP8B1): c.2097+2T> C single nucleotide variant Pathogenic rs387906381 GRCh38 Chromosome 18, 57669316: 57669316
9 ATP8B1 ATP8B1, 1.4-KB DEL deletion Pathogenic
10 ATP8B1 NM_005603.4(ATP8B1): c.1982T> C (p.Ile661Thr) single nucleotide variant Pathogenic rs121909100 GRCh37 Chromosome 18, 55336665: 55336665
11 ATP8B1 NM_005603.4(ATP8B1): c.1982T> C (p.Ile661Thr) single nucleotide variant Pathogenic rs121909100 GRCh38 Chromosome 18, 57669433: 57669433
12 ATP8B1 NM_005603.5(ATP8B1): c.1660G> A (p.Asp554Asn) single nucleotide variant Pathogenic rs121909101 GRCh37 Chromosome 18, 55342225: 55342225
13 ATP8B1 NM_005603.5(ATP8B1): c.1660G> A (p.Asp554Asn) single nucleotide variant Pathogenic rs121909101 GRCh38 Chromosome 18, 57674993: 57674993
14 ATP8B1 NM_005603.5(ATP8B1): c.208G> A (p.Asp70Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs34719006 GRCh37 Chromosome 18, 55373793: 55373793
15 ATP8B1 NM_005603.5(ATP8B1): c.208G> A (p.Asp70Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs34719006 GRCh38 Chromosome 18, 57706561: 57706561
16 ATP8B1 NM_005603.5(ATP8B1): c.1367C> T (p.Thr456Met) single nucleotide variant Pathogenic rs121909104 GRCh37 Chromosome 18, 55355593: 55355593
17 ATP8B1 NM_005603.5(ATP8B1): c.1367C> T (p.Thr456Met) single nucleotide variant Pathogenic rs121909104 GRCh38 Chromosome 18, 57688361: 57688361
18 ATP8B1 NM_005603.5(ATP8B1): c.1804C> T (p.Arg602Ter) single nucleotide variant Pathogenic rs121909105 GRCh37 Chromosome 18, 55342081: 55342081
19 ATP8B1 NM_005603.5(ATP8B1): c.1804C> T (p.Arg602Ter) single nucleotide variant Pathogenic rs121909105 GRCh38 Chromosome 18, 57674849: 57674849
20 ATP8B1 NM_005603.4(ATP8B1): c.1993G> T (p.Glu665Ter) single nucleotide variant Pathogenic rs515726137 GRCh37 Chromosome 18, 55336654: 55336654
21 ATP8B1 NM_005603.4(ATP8B1): c.1993G> T (p.Glu665Ter) single nucleotide variant Pathogenic rs515726137 GRCh38 Chromosome 18, 57669422: 57669422
22 ATP8B1 NM_005603.5(ATP8B1): c.625C> A (p.Pro209Thr) single nucleotide variant Pathogenic rs515726138 GRCh38 Chromosome 18, 57697797: 57697797
23 ATP8B1 NM_005603.5(ATP8B1): c.625C> A (p.Pro209Thr) single nucleotide variant Pathogenic rs515726138 GRCh37 Chromosome 18, 55365029: 55365029
24 ABCB4 NM_000443.3(ABCB4): c.504C> T (p.Asn168=) single nucleotide variant Benign rs1202283 GRCh37 Chromosome 7, 87082292: 87082292
25 ABCB4 NM_000443.3(ABCB4): c.504C> T (p.Asn168=) single nucleotide variant Benign rs1202283 GRCh38 Chromosome 7, 87452976: 87452976
26 NR1H4 NM_005123.3(NR1H4): c.419_420insAAA (p.Tyr139_Asn140insLys) insertion Pathogenic rs879255644 GRCh37 Chromosome 12, 100904895: 100904896
27 NR1H4 NM_005123.3(NR1H4): c.419_420insAAA (p.Tyr139_Asn140insLys) insertion Pathogenic rs879255644 GRCh38 Chromosome 12, 100511117: 100511118
28 NR1H4 NM_005123.3(NR1H4): c.526C> T (p.Arg176Ter) single nucleotide variant Pathogenic rs113090017 GRCh37 Chromosome 12, 100926316: 100926316
29 NR1H4 NM_005123.3(NR1H4): c.526C> T (p.Arg176Ter) single nucleotide variant Pathogenic rs113090017 GRCh38 Chromosome 12, 100532538: 100532538
30 NR1H4 NC_000012.11: g.100886254_100917988del31735 deletion Pathogenic GRCh37 Chromosome 12, 100886254: 100917988
31 ABCB4 NM_000443.3(ABCB4): c.1954A> G (p.Arg652Gly) single nucleotide variant Benign rs2230028 GRCh38 Chromosome 7, 87426860: 87426860
32 ABCB4 NM_000443.3(ABCB4): c.1954A> G (p.Arg652Gly) single nucleotide variant Benign rs2230028 GRCh37 Chromosome 7, 87056176: 87056176
33 ABCB4 NM_000443.3(ABCB4): c.1893+6T> C single nucleotide variant Conflicting interpretations of pathogenicity rs8187798 GRCh37 Chromosome 7, 87060714: 87060714
34 ABCB4 NM_000443.3(ABCB4): c.1893+6T> C single nucleotide variant Conflicting interpretations of pathogenicity rs8187798 GRCh38 Chromosome 7, 87431398: 87431398
35 ABCB4 NM_000443.3(ABCB4): c.711A> T (p.Ile237=) single nucleotide variant Benign/Likely benign rs2109505 GRCh37 Chromosome 7, 87079406: 87079406
36 ABCB4 NM_000443.3(ABCB4): c.711A> T (p.Ile237=) single nucleotide variant Benign/Likely benign rs2109505 GRCh38 Chromosome 7, 87450090: 87450090
37 ABCB4 NM_000443.3(ABCB4): c.459T> C (p.Phe153=) single nucleotide variant Benign/Likely benign rs2230027 GRCh37 Chromosome 7, 87082337: 87082337
38 ABCB4 NM_000443.3(ABCB4): c.459T> C (p.Phe153=) single nucleotide variant Benign/Likely benign rs2230027 GRCh38 Chromosome 7, 87453021: 87453021
39 ABCB4 NM_000443.3(ABCB4): c.175C> T (p.Leu59=) single nucleotide variant Benign rs2302387 GRCh37 Chromosome 7, 87092185: 87092185
40 ABCB4 NM_000443.3(ABCB4): c.175C> T (p.Leu59=) single nucleotide variant Benign rs2302387 GRCh38 Chromosome 7, 87462869: 87462869
41 ABCB4 NM_000443.3(ABCB4): c.147C> T (p.Ser49=) single nucleotide variant Benign/Likely benign rs8187789 GRCh37 Chromosome 7, 87092213: 87092213
42 ABCB4 NM_000443.3(ABCB4): c.147C> T (p.Ser49=) single nucleotide variant Benign/Likely benign rs8187789 GRCh38 Chromosome 7, 87462897: 87462897
43 ABCB4 NM_000443.3(ABCB4): c.-1G> A single nucleotide variant Benign/Likely benign rs45449704 GRCh37 Chromosome 7, 87104782: 87104782
44 ABCB4 NM_000443.3(ABCB4): c.-1G> A single nucleotide variant Benign/Likely benign rs45449704 GRCh38 Chromosome 7, 87475466: 87475466
45 ABCB4 NM_000443.3(ABCB4): c.3037A> C (p.Arg1013=) single nucleotide variant Conflicting interpretations of pathogenicity rs2230029 GRCh37 Chromosome 7, 87038596: 87038596
46 ABCB4 NM_000443.3(ABCB4): c.3037A> C (p.Arg1013=) single nucleotide variant Conflicting interpretations of pathogenicity rs2230029 GRCh38 Chromosome 7, 87409280: 87409280
47 ATP8B1 NM_005603.5(ATP8B1): c.3410C> G (p.Ser1137Ter) single nucleotide variant Pathogenic rs74414989 GRCh37 Chromosome 18, 55317720: 55317720
48 ATP8B1 NM_005603.5(ATP8B1): c.3410C> G (p.Ser1137Ter) single nucleotide variant Pathogenic rs74414989 GRCh38 Chromosome 18, 57650488: 57650488
49 ATP8B1 NM_005603.5(ATP8B1): c.279G> A (p.Ala93=) single nucleotide variant Pathogenic rs761575295 GRCh37 Chromosome 18, 55373722: 55373722
50 ATP8B1 NM_005603.5(ATP8B1): c.279G> A (p.Ala93=) single nucleotide variant Pathogenic rs761575295 GRCh38 Chromosome 18, 57706490: 57706490

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 COSM521 KRAS biliary tract,gallbladder,other,metaplasia c.35G>A p.G12D 12:25245350-25245350 2

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
12.86 ABCB4 ABCG5 ABCG8 ATP11C ATP8B1 MYO5B
2
Show member pathways
11.82 ABCB11 NR1H4 SLC10A2
3
Show member pathways
11.57 ABCB11 ABCG5 ABCG8
4
Show member pathways
11.1 ABCG5 ABCG8
5 11.08 ABCG5 ABCG8
6 11.02 ABCB11 ABCB4 ABCG5 ABCG8 NR0B2 NR1H4
7 11 ABCB11 ABCB4 ABCG5 NR1H4
8 10.6 ABCB11 NR1H4
9 10.54 ABCB11 ABCB4 NR0B2 NR1H4

GO Terms for Cholestasis, Progressive Familial Intrahepatic, 1

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

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.97 ABCB11 ABCB4 ABCG5 ABCG8 ATP11C ATP8B1
2 apical part of cell GO:0045177 9.5 ABCB11 ABCG5 JAG1
3 integral component of plasma membrane GO:0005887 9.5 ABCB11 ABCB4 ABCG5 ABCG8 ATP8B1 JAG1
4 ATP-binding cassette (ABC) transporter complex GO:0043190 9.26 ABCG5 ABCG8
5 intercellular canaliculus GO:0046581 9.16 ABCB11 ABCB4
6 apical plasma membrane GO:0016324 9.1 ABCB4 ABCG5 ABCG8 ATP8B1 JAG1 SLC10A2

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

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.83 ABCB11 ABCB4 ABCG5 ABCG8 SLC10A2
2 response to drug GO:0042493 9.74 ABCB4 ABCG5 ABCG8
3 Notch signaling pathway GO:0007219 9.69 JAG1 NR0B2 NR1H4
4 cholesterol homeostasis GO:0042632 9.63 ABCG5 ABCG8 NR1H4
5 phospholipid transport GO:0015914 9.58 ABCG8 ATP11C ATP8B1
6 steroid hormone mediated signaling pathway GO:0043401 9.56 NR0B2 NR1H4
7 lipid homeostasis GO:0055088 9.55 ABCB4 NR1H4
8 lipid transport GO:0006869 9.55 ABCB4 ABCG5 ABCG8 ATP11C ATP8B1
9 excretion GO:0007588 9.54 ABCG5 ABCG8
10 cholesterol efflux GO:0033344 9.52 ABCG5 ABCG8
11 bile acid metabolic process GO:0008206 9.49 ATP8B1 NR1H4
12 intestinal cholesterol absorption GO:0030299 9.48 ABCG5 ABCG8
13 phospholipid translocation GO:0045332 9.43 ABCB4 ATP11C ATP8B1
14 negative regulation of intestinal cholesterol absorption GO:0045796 9.37 ABCG5 ABCG8
15 negative regulation of intestinal phytosterol absorption GO:0010949 9.32 ABCG5 ABCG8
16 bile acid and bile salt transport GO:0015721 9.26 ABCB11 ATP8B1 NR1H4 SLC10A2
17 drug transmembrane transport GO:0006855 8.92 ABCB4 ABCG5 ABCG8 ATP8B1

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

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.5 ABCB11 ABCB4 ABCG5 ABCG8 ATP11C ATP8B1
2 ATPase activity GO:0016887 9.46 ABCB11 ABCB4 ABCG5 ABCG8
3 steroid hormone receptor activity GO:0003707 9.43 NR0B2 NR1H4
4 cholesterol transporter activity GO:0017127 9.4 ABCG5 ABCG8
5 phospholipid-translocating ATPase activity GO:0004012 9.37 ATP11C ATP8B1
6 retinoid X receptor binding GO:0046965 9.32 NR0B2 NR1H4
7 drug transmembrane transporter activity GO:0015238 9.26 ABCG5 ABCG8
8 ATPase activity, coupled to transmembrane movement of substances GO:0042626 8.92 ABCB11 ABCB4 ABCG5 ABCG8

Sources for Cholestasis, Progressive Familial Intrahepatic, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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