MCID: CHL132
MIFTS: 52

Cholestasis, Progressive Familial Intrahepatic, 1

Categories: Genetic diseases, Rare diseases, Liver diseases, Metabolic diseases, Reproductive diseases, Gastrointestinal diseases, Endocrine 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 25 59 75 55
Pfic1 57 53 59 75
Cholestasis, Progressive Familial Intrahepatic 1 57 76 13
Progressive Familial Intrahepatic Cholestasis 53 25 59
Abcb4-Related Intrahepatic Cholestasis 25 6
Fic1 Deficiency 25 59
Cholestasis, Intrahepatic, Familial, Progressive, Type 1 40
Progressive Familial Intrahepatic Cholestasis Type 1 59
Cholestasis, Progressive Familial Intrahepatic 3 73
Cholestasis, Intrahepatic, Familial, Progressive 40
Progressive Familial Intrahepatic Cholestasis 1 53
Low Γ-Gt Familial Intrahepatic Cholestasis 25
Abcb11-Related Intrahepatic Cholestasis 25
Atp8b1-Related Intrahepatic Cholestasis 25
Progressive Intrahepatic Cholestasis 73
Cholestasis, Fatal Intrahepatic 53
Fatal Intrahepatic Cholestasis 75
Severe Atp8b1 Deficiency 53
Mdr3 Deficiency 25
Byler's Disease 53
Bsep Deficiency 25
Byler Syndrome 25
Pfic 59

Characteristics:

Orphanet epidemiological data:

59
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;

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:



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, 2 and cholestasis, benign recurrent intrahepatic, 1, and has symptoms including diarrhea, icterus and pruritus. 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 Pharmaceutical Solutions and Liver Extracts have been mentioned in the context of this disorder. Affiliated tissues include liver and bone, and related phenotypes are failure to thrive and splenomegaly

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.

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 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 25)
# Related Disease Score Top Affiliating Genes
1 cholestasis, progressive familial intrahepatic, 2 32.9 ABCB11 ABCB4 ATP8B1
2 cholestasis, benign recurrent intrahepatic, 1 32.0 ABCB11 ATP8B1
3 cholestasis, progressive familial intrahepatic, 3 31.6 ABCB11 ABCB4 ATP8B1 JAG1
4 atp8b1 deficiency 31.2 ABCB11 ATP8B1 NR1H4
5 intrahepatic cholestasis 25.4 ABCB11 ABCB4 ATP8B1 GGT1 JAG1 NR1H4
6 cholestasis 25.4 ABCB11 ABCB4 ATP8B1 GGT1 JAG1 NR1H4
7 myo5b-related progressive familial intrahepatic cholestasis 12.2
8 bile acid synthesis defect, congenital, 1 11.8
9 cholestasis, progressive familial intrahepatic, 4 11.5
10 cholestasis, progressive familial intrahepatic, 5 10.9
11 cholelithiasis 10.0 ABCB4 NR1H4
12 extrahepatic cholestasis 9.9 ABCB4 GGT1
13 familial mediterranean fever 9.8
14 brucellosis 9.8
15 cholangitis, primary sclerosing 9.7 ABCB4 GGT1
16 biliary atresia, extrahepatic 9.6 GGT1 JAG1
17 primary biliary cirrhosis 9.5 ABCB4 GGT1 NR1H4
18 sclerosing cholangitis 9.4 ABCB11 ABCB4 GGT1
19 cholangitis 9.4 ABCB11 ABCB4 GGT1
20 gastrointestinal system disease 9.3 ABCB11 GGT1
21 alagille syndrome 1 9.3 ABCB4 ATP8B1 JAG1
22 biliary atresia 8.7 ATP8B1 JAG1 NR1H4 SLC10A2
23 liver disease 8.6 ABCB11 ABCB4 ATP8B1 GGT1 NR1H4
24 bile duct disease 7.9 ABCB11 ABCB4 ATP8B1 GGT1 NR1H4 SLC10A2
25 biliary tract disease 7.9 ABCB11 ABCB4 ATP8B1 GGT1 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

AbdomenSpleen:
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:

59 32 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
2 splenomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001744
3 hepatomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0002240
4 delayed skeletal maturation 59 32 frequent (33%) Frequent (79-30%) HP:0002750
5 malabsorption 59 32 hallmark (90%) Very frequent (99-80%) HP:0002024
6 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
7 cognitive impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0100543
8 neoplasm 59 32 occasional (7.5%) Occasional (29-5%) HP:0002664
9 reduced bone mineral density 59 32 frequent (33%) Frequent (79-30%) HP:0004349
10 jaundice 59 32 hallmark (90%) Very frequent (99-80%) HP:0000952
11 hypocalcemia 59 32 frequent (33%) Frequent (79-30%) HP:0002901
12 abnormality of coagulation 59 32 hallmark (90%) Very frequent (99-80%) HP:0001928
13 pruritus 32 HP:0000989
14 cirrhosis 32 HP:0001394
15 abnormality of thrombocytes 59 Frequent (79-30%)
16 cholestasis 59 Very frequent (99-80%)
17 diarrhea 32 HP:0002014
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
22 abnormal thrombocyte morphology 32 frequent (33%) HP:0001872

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
# 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 growth/size/body region MP:0005378 9.76 SLC10A2 ABCB11 ABCB4 ATP8B1 GGT1 JAG1
2 digestive/alimentary MP:0005381 9.65 NR1H4 SLC10A2 ABCB4 JAG1 MYO5B
3 homeostasis/metabolism MP:0005376 9.56 SLC10A2 ABCB11 ABCB4 ATP8B1 GGT1 JAG1
4 liver/biliary system MP:0005370 9.1 SLC10A2 ABCB11 ABCB4 ATP8B1 JAG1 NR1H4

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 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
Pancrelipase Approved, Investigational 53608-75-6
11
Iron Approved 7439-89-6 23925
12
Glycerol Approved, Investigational 56-81-5 753
13 pancreatin
14 Alpha 1-Antitrypsin
15 Estrogens
16 Protein C Inhibitor
17
Bilirubin 635-65-4 5280352
18 Gastrointestinal Agents
19 Hematinics
20 4-phenylbutyric acid
21 Protective Agents

Interventional clinical trials:

(show all 14)
# 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 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
3 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
4 An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects Completed NCT03082937 Phase 1 3 mg [14C]-A4250 capsule
5 A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384 Completed NCT02963077 Phase 1 A4250;CRC (A3384);Questran;Placebo
6 Validation of the Itch Reported Outcome (ItchRO) Diaries in Pediatric Cholestatic Liver Disease Completed NCT02131623
7 ABCB4 Gene Mutations in Intrahepatic Cholestasis of Pregnancy and Controls Completed NCT00700232
8 Shear Wave Sonoelastography in Pediatric Liver Fibrosis Completed NCT02372682
9 Evaluating the Genetic Causes and Progression of Cholestatic Liver Diseases (LOGIC) Recruiting NCT00571272
10 Sulfation of Bile Acids as a Biomarker for Hepatobiliary Diseases Recruiting NCT01200082
11 China Registry for Genetic / Metabolic Liver Diseases Recruiting NCT03131427 Standard of care
12 Buphenyl Therapy for Byler's Disease No longer available NCT01784718 Buphenyl
13 Transition From Buphenyl to RAVICTI for the Therapy of Byler Disease No longer available NCT01949766 Glycerol phenylbutyrate
14 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

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

Publications for Cholestasis, Progressive Familial Intrahepatic, 1

Articles related to Cholestasis, Progressive Familial Intrahepatic, 1:

# Title Authors Year
1
Multiple Looser zones of osteomalacia in Byler disease with associated vitamin D deficiency, phosphaturia, and elevated FGF23. ( 26771453 )
2016
2
[Progressive familial intrahepatic cholestasis (Byler disease): current genetics and therapy]. ( 10812555 )
2000
3
Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): evidence for heterogeneity. ( 9214465 )
1997
4
Mapping of a locus for progressive familial intrahepatic cholestasis (Byler disease) to 18q21-q22, the benign recurrent intrahepatic cholestasis region. ( 7655458 )
1995
5
Evidence for defective primary bile acid secretion in children with progressive familial intrahepatic cholestasis (Byler disease). ( 8088298 )
1994
6
Orthotopic liver transplantation for Byler disease. ( 2238055 )
1990
7
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
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 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.1367C> T (p.Thr456Met) single nucleotide variant Pathogenic rs121909104 GRCh37 Chromosome 18, 55355593: 55355593
15 ATP8B1 NM_005603.5(ATP8B1): c.1367C> T (p.Thr456Met) single nucleotide variant Pathogenic rs121909104 GRCh38 Chromosome 18, 57688361: 57688361
16 ATP8B1 NM_005603.5(ATP8B1): c.1804C> T (p.Arg602Ter) single nucleotide variant Pathogenic rs121909105 GRCh37 Chromosome 18, 55342081: 55342081
17 ATP8B1 NM_005603.5(ATP8B1): c.1804C> T (p.Arg602Ter) single nucleotide variant Pathogenic rs121909105 GRCh38 Chromosome 18, 57674849: 57674849
18 ATP8B1 NM_005603.4(ATP8B1): c.1993G> T (p.Glu665Ter) single nucleotide variant Pathogenic rs515726137 GRCh37 Chromosome 18, 55336654: 55336654
19 ATP8B1 NM_005603.4(ATP8B1): c.1993G> T (p.Glu665Ter) single nucleotide variant Pathogenic rs515726137 GRCh38 Chromosome 18, 57669422: 57669422
20 ATP8B1 NM_005603.5(ATP8B1): c.625C> A (p.Pro209Thr) single nucleotide variant Pathogenic rs515726138 GRCh38 Chromosome 18, 57697797: 57697797
21 ATP8B1 NM_005603.5(ATP8B1): c.625C> A (p.Pro209Thr) single nucleotide variant Pathogenic rs515726138 GRCh37 Chromosome 18, 55365029: 55365029
22 ABCB4 NM_000443.3(ABCB4): c.140G> A (p.Arg47Gln) single nucleotide variant Uncertain significance rs372685632 GRCh37 Chromosome 7, 87092220: 87092220
23 ABCB4 NM_000443.3(ABCB4): c.140G> A (p.Arg47Gln) single nucleotide variant Uncertain significance rs372685632 GRCh38 Chromosome 7, 87462904: 87462904
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

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:

# 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:

# Name GO ID Score Top Affiliating Genes
1 lipid homeostasis GO:0055088 9.32 ABCB4 NR1H4
2 drug transmembrane transport GO:0006855 9.26 ABCB4 ATP8B1
3 phospholipid translocation GO:0045332 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:

# 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
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
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42 MedGen
44 MeSH
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46 MGI
49 NCI
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51 NDF-RT
54 NINDS
55 Novoseek
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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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