PFIC3
MCID: CHL137
MIFTS: 46

Cholestasis, Progressive Familial Intrahepatic, 3 (PFIC3)

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

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic, 3

MalaCards integrated aliases for Cholestasis, Progressive Familial Intrahepatic, 3:

Name: Cholestasis, Progressive Familial Intrahepatic, 3 58 76
Pfic3 58 12 54 60 76 56
Cholestasis, Progressive Familial Intrahepatic 3 58 77 13 45 74
Progressive Familial Intrahepatic Cholestasis 3 12 30 6 15
Mdr3 Deficiency 58 12 54 76
Progressive Familial Intrahepatic Cholestasis with Elevated Serum Gamma-Glutamyltransferase 54 76
Progressive Familial Intrahepatic Cholestasis Type 3 54 60
Cholestasis, Progressive Familial Intrahepatic, with Elevated Serum Gamma-Glutamyltransferase 58
Progressive Familial Intrahepatic Cholestasis with Elevated Serum Gama-Glutamyltransferase 12
Cholestasis, Intrahepatic, Familial, Progressive, Type 3 41

Characteristics:

Orphanet epidemiological data:

60
progressive familial intrahepatic cholestasis type 3
Inheritance: Autosomal recessive; Age of onset: All ages;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in early infancy
genetic heterogeneity (see pfic1, )
carrier females may develop intrahepatic cholestasis of pregnancy (icp, )


HPO:

33
cholestasis, progressive familial intrahepatic, 3:
Onset and clinical course infantile onset
Inheritance heterogeneous autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0070223
OMIM 58 602347
MESH via Orphanet 46 C535935
ICD10 via Orphanet 35 K76.8
UMLS via Orphanet 75 C1865643
Orphanet 60 ORPHA79305
MedGen 43 C1865643
UMLS 74 C1865643

Summaries for Cholestasis, Progressive Familial Intrahepatic, 3

NIH Rare Diseases : 54 Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare condition that affects the liver. People with this condition generally develop signs and symptoms during late infancy or early childhood, which may include severe itching, jaundice, failure to thrive, portal hypertension (high blood pressure in the vein that provides blood to the liver) and hepatosplenomegaly (enlarged liver and spleen). The condition may progress to liver failure during childhood or adulthood. PFIC3 is caused by change (mutations) in the ABCB4 gene and is inherited in an autosomal recessive manner. Treatment may include ursodeoxycholic acid therapy to prevent liver damage, surgery and/or liver transplantation.

MalaCards based summary : Cholestasis, Progressive Familial Intrahepatic, 3, also known as pfic3, is related to cholestasis, benign recurrent intrahepatic, 1 and cholestasis, progressive familial intrahepatic, 1, and has symptoms including pruritus, diarrhea and icterus. An important gene associated with Cholestasis, Progressive Familial Intrahepatic, 3 is ABCB4 (ATP Binding Cassette Subfamily B Member 4), and among its related pathways/superpathways are Hepatic ABC Transporters and Bile secretion. The drugs Gastrointestinal Agents and Bile Acids and Salts have been mentioned in the context of this disorder. Affiliated tissues include liver, spleen and testes, and related phenotypes are splenomegaly and hepatomegaly

Disease Ontology : 12 A progressive familial intrahepatic cholestasis characterized by autosomal recessive inheritance of intrahepatic cholestasis and elevated serum GGT1 activity that has material basis in mutation in the ABCB4 gene on chromosome 7q21.12.

UniProtKB/Swiss-Prot : 76 Cholestasis, progressive familial intrahepatic, 3: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood.

Wikipedia : 77 Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions... more...

Description from OMIM: 602347

Related Diseases for Cholestasis, Progressive Familial Intrahepatic, 3

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

(show all 20)
# Related Disease Score Top Affiliating Genes
1 cholestasis, benign recurrent intrahepatic, 1 31.8 ABCB11 ATP11C ATP8B1
2 cholestasis, progressive familial intrahepatic, 1 31.0 ABCB11 ABCB4 ATP11C ATP8B1 JAG1
3 progressive familial intrahepatic cholestasis 29.9 ABCB11 ABCB4 ATP8B1
4 biliary atresia 29.7 ATP8B1 JAG1
5 cholestasis 29.4 ABCB11 ABCB4 ATP8B1 JAG1
6 gallbladder disease 1 11.1
7 wilson disease 10.3
8 liver cirrhosis 10.3
9 cholelithiasis 10.1
10 atp8b1 deficiency 10.0 ABCB11 ATP8B1
11 cholestasis, benign recurrent intrahepatic, 2 10.0 ABCB11 ATP8B1
12 sclerosing cholangitis 9.9 ABCB11 ABCB4
13 cholangitis 9.9 ABCB11 ABCB4
14 cholestasis, progressive familial intrahepatic, 4 9.8 ABCB11 ABCB4 ATP8B1
15 cholestasis, progressive familial intrahepatic, 2 9.8 ABCB11 ABCB4 ATP8B1
16 bile duct disease 9.8 ABCB11 ABCB4 ATP8B1
17 biliary tract disease 9.8 ABCB11 ABCB4 ATP8B1
18 liver disease 9.7 ABCB11 ABCB4 ATP8B1
19 alagille syndrome 1 9.5 ABCB11 ABCB4 ATP8B1 JAG1
20 intrahepatic cholestasis of pregnancy 9.4 ABCB11 ABCB4 ATP8B1 JAG1

Graphical network of the top 20 diseases related to Cholestasis, Progressive Familial Intrahepatic, 3:



Diseases related to Cholestasis, Progressive Familial Intrahepatic, 3

Symptoms & Phenotypes for Cholestasis, Progressive Familial Intrahepatic, 3

Human phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 3:

33 (show all 11)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 33 HP:0001744
2 hepatomegaly 33 HP:0002240
3 malabsorption 33 HP:0002024
4 pruritus 33 HP:0000989
5 elevated hepatic transaminase 33 HP:0002910
6 cirrhosis 33 HP:0001394
7 jaundice 33 HP:0000952
8 diarrhea 33 HP:0002014
9 intrahepatic cholestasis 33 HP:0001406
10 portal fibrosis 33 HP:0006580
11 bile duct proliferation 33 HP:0001408

Symptoms via clinical synopsis from OMIM:

58
Abdomen Spleen:
splenomegaly

Skin Nails Hair Skin:
pruritus
jaundice

Laboratory Abnormalities:
abnormal liver function tests
increased serum bile acids
increased serum gamma-ggt

Abdomen Liver:
hepatomegaly
cirrhosis
jaundice
intrahepatic cholestasis
end-stage liver disease before adulthood
more
Abdomen Gastrointestinal:
diarrhea
malabsorption of fat and fat-soluble vitamins

Clinical features from OMIM:

602347

UMLS symptoms related to Cholestasis, Progressive Familial Intrahepatic, 3:


pruritus, diarrhea, icterus

GenomeRNAi Phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 3 according to GeneCards Suite gene sharing:

27
# 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, 3:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 liver/biliary system MP:0005370 8.92 ABCB11 ABCB4 ATP8B1 JAG1

Drugs & Therapeutics for Cholestasis, Progressive Familial Intrahepatic, 3

Drugs for Cholestasis, Progressive Familial Intrahepatic, 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Gastrointestinal Agents Not Applicable
2 Bile Acids and Salts Not Applicable
3 Lecithin Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Second-line Therapy of Unresectable Cholangiocarcinoma by RADIOEMBOLIZATION Terminated NCT01383746 Phase 1, Phase 2
2 Intralumenal Effects on Cholesterol Absorption/Synthesis Completed NCT00328211 Not Applicable Pluronic F-68

Search NIH Clinical Center for Cholestasis, Progressive Familial Intrahepatic, 3

Cochrane evidence based reviews: cholestasis, progressive familial intrahepatic 3

Genetic Tests for Cholestasis, Progressive Familial Intrahepatic, 3

Genetic tests related to Cholestasis, Progressive Familial Intrahepatic, 3:

# Genetic test Affiliating Genes
1 Progressive Familial Intrahepatic Cholestasis 3 30 ABCB4

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic, 3

MalaCards organs/tissues related to Cholestasis, Progressive Familial Intrahepatic, 3:

42
Liver, Spleen, Testes

Publications for Cholestasis, Progressive Familial Intrahepatic, 3

Articles related to Cholestasis, Progressive Familial Intrahepatic, 3:

# Title Authors Year
1
Phenotypic variability in Tunisian PFIC3 patients harboring a complex genotype with a differential clinical outcome of UDCA treatment. ( 30036524 )
2018
2
A Novel Mutation of ABCB4 in Progressive Familial Intrahepatic Cholestasis 3: Like Mother, Like Daughter. ( 26796082 )
2016
3
In silico investigation of the impact of synonymous variants in ABCB4 gene on mRNA stability/structure, splicing accuracy and codon usage: Potential contribution to PFIC3 disease. ( 27788395 )
2016
4
Combined features of low phospholipid-associated cholelithiasis and progressive familial intrahepatic cholestasis 3. ( 19840255 )
2010
5
Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3). ( 17726488 )
2007
6
Heterozygous non-sense mutation of the MDR3 gene in familial intrahepatic cholestasis of pregnancy. ( 9923886 )
1999
7
Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. ( 9419367 )
1998
8
Defect of multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis. ( 8666348 )
1996

Variations for Cholestasis, Progressive Familial Intrahepatic, 3

UniProtKB/Swiss-Prot genetic disease variations for Cholestasis, Progressive Familial Intrahepatic, 3:

76 (show all 39)
# Symbol AA change Variation ID SNP ID
1 ABCB4 p.Trp138Arg VAR_043080 rs72552781
2 ABCB4 p.Ser346Ile VAR_043084 rs67876345
3 ABCB4 p.Glu395Gly VAR_043086 rs72552777
4 ABCB4 p.Thr424Ala VAR_043087 rs126356547
5 ABCB4 p.Val425Met VAR_043088
6 ABCB4 p.Gly535Asp VAR_043091
7 ABCB4 p.Ile541Phe VAR_043092 rs66904256
8 ABCB4 p.Leu556Arg VAR_043093
9 ABCB4 p.Asp564Gly VAR_043094
10 ABCB4 p.Phe711Ser VAR_043097 rs72552773
11 ABCB4 p.Gly983Ser VAR_043103 rs56187107
12 ABCB4 p.Gly68Arg VAR_073731 rs134366790
13 ABCB4 p.Gly70Arg VAR_073732
14 ABCB4 p.Leu73Val VAR_073734 rs8187788
15 ABCB4 p.Gly126Glu VAR_073738 rs102198837
16 ABCB4 p.Thr201Met VAR_073740 rs753318087
17 ABCB4 p.Ala250Pro VAR_073741
18 ABCB4 p.Ala286Val VAR_073742 rs765478923
19 ABCB4 p.Phe357Leu VAR_073743
20 ABCB4 p.Ala364Val VAR_073744
21 ABCB4 p.Tyr403His VAR_073745 rs121918443
22 ABCB4 p.Asp459His VAR_073748
23 ABCB4 p.Val475Ala VAR_073749
24 ABCB4 p.Pro479Leu VAR_073750 rs748657435
25 ABCB4 p.Leu481Arg VAR_073751
26 ABCB4 p.Ala511Thr VAR_073753 rs125788715
27 ABCB4 p.Glu558Lys VAR_073757
28 ABCB4 p.Thr593Ala VAR_073759
29 ABCB4 p.Met630Val VAR_073761 rs372476723
30 ABCB4 p.Leu701Pro VAR_073763 rs988987669
31 ABCB4 p.Thr715Ile VAR_073764 rs138773456
32 ABCB4 p.Gly723Glu VAR_073765
33 ABCB4 p.Pro726Thr VAR_073767
34 ABCB4 p.Ala737Val VAR_073769 rs147134978
35 ABCB4 p.Ala840Asp VAR_073770
36 ABCB4 p.Gly954Ser VAR_073771 rs779829759
37 ABCB4 p.Ser978Pro VAR_073774 rs105186118
38 ABCB4 p.Glu1125Lys VAR_073776
39 ABCB4 p.Ala1193Thr VAR_073777

ClinVar genetic disease variations for Cholestasis, Progressive Familial Intrahepatic, 3:

6 (show all 34)
# Gene Variation Type Significance SNP ID Assembly Location
1 ABCB4 NM_018849.2(ABCB4): c.394_400delTATATAC (p.Tyr132Lysfs) deletion Pathogenic rs387906526 GRCh37 Chromosome 7, 87082396: 87082402
2 ABCB4 NM_018849.2(ABCB4): c.394_400delTATATAC (p.Tyr132Lysfs) deletion Pathogenic rs387906526 GRCh38 Chromosome 7, 87453080: 87453086
3 ABCB4 NM_018849.2(ABCB4): c.2869C> T (p.Arg957Ter) single nucleotide variant Pathogenic rs121918440 GRCh37 Chromosome 7, 87041264: 87041264
4 ABCB4 NM_018849.2(ABCB4): c.2869C> T (p.Arg957Ter) single nucleotide variant Pathogenic rs121918440 GRCh38 Chromosome 7, 87411948: 87411948
5 ABCB4 NM_018849.2(ABCB4): c.1712delT (p.Val571Aspfs) deletion Pathogenic rs387906527 GRCh37 Chromosome 7, 87069002: 87069002
6 ABCB4 NM_018849.2(ABCB4): c.1712delT (p.Val571Aspfs) deletion Pathogenic rs387906527 GRCh38 Chromosome 7, 87439686: 87439686
7 ABCB4 NM_000443.3(ABCB4): c.959C> T (p.Ser320Phe) single nucleotide variant Conflicting interpretations of pathogenicity rs72552778 GRCh37 Chromosome 7, 87076396: 87076396
8 ABCB4 NM_000443.3(ABCB4): c.959C> T (p.Ser320Phe) single nucleotide variant Conflicting interpretations of pathogenicity rs72552778 GRCh38 Chromosome 7, 87447080: 87447080
9 ABCB4 NM_018849.2(ABCB4): c.2169dupG (p.Leu724Alafs) duplication Pathogenic rs387906529 GRCh37 Chromosome 7, 87053264: 87053264
10 ABCB4 NM_018849.2(ABCB4): c.2169dupG (p.Leu724Alafs) duplication Pathogenic rs387906529 GRCh38 Chromosome 7, 87423948: 87423948
11 ABCB4 NM_018849.2(ABCB4): c.1207T> C (p.Tyr403His) single nucleotide variant Pathogenic rs121918443 GRCh37 Chromosome 7, 87073002: 87073002
12 ABCB4 NM_018849.2(ABCB4): c.1207T> C (p.Tyr403His) single nucleotide variant Pathogenic rs121918443 GRCh38 Chromosome 7, 87443686: 87443686
13 ABCB4 NM_000443.3(ABCB4): c.1769G> A (p.Arg590Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs45575636 GRCh37 Chromosome 7, 87060844: 87060844
14 ABCB4 NM_000443.3(ABCB4): c.1769G> A (p.Arg590Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs45575636 GRCh38 Chromosome 7, 87431528: 87431528
15 ABCB4 NM_018849.2(ABCB4): c.2906G> A (p.Arg969His) single nucleotide variant Uncertain significance rs752916287 GRCh37 Chromosome 7, 87041227: 87041227
16 ABCB4 NM_018849.2(ABCB4): c.2906G> A (p.Arg969His) single nucleotide variant Uncertain significance rs752916287 GRCh38 Chromosome 7, 87411911: 87411911
17 ABCB4 NM_018849.2(ABCB4): c.101C> T (p.Thr34Met) single nucleotide variant Uncertain significance rs142794414 GRCh37 Chromosome 7, 87101971: 87101971
18 ABCB4 NM_018849.2(ABCB4): c.101C> T (p.Thr34Met) single nucleotide variant Uncertain significance rs142794414 GRCh38 Chromosome 7, 87472655: 87472655
19 ABCB4 NM_018849.2(ABCB4): c.1210C> G (p.Pro404Ala) single nucleotide variant no interpretation for the single variant rs863225298 GRCh37 Chromosome 7, 87072999: 87072999
20 ABCB4 NM_018849.2(ABCB4): c.1210C> G (p.Pro404Ala) single nucleotide variant no interpretation for the single variant rs863225298 GRCh38 Chromosome 7, 87443683: 87443683
21 ABCB4 NM_018849.2(ABCB4): c.431G> A (p.Arg144Gln) single nucleotide variant Uncertain significance rs863225299 GRCh37 Chromosome 7, 87082365: 87082365
22 ABCB4 NM_018849.2(ABCB4): c.431G> A (p.Arg144Gln) single nucleotide variant Uncertain significance rs863225299 GRCh38 Chromosome 7, 87453049: 87453049
23 ABCB4 NM_000443.3(ABCB4): c.1954A> G (p.Arg652Gly) single nucleotide variant Benign rs2230028 GRCh38 Chromosome 7, 87426860: 87426860
24 ABCB4 NM_000443.3(ABCB4): c.1954A> G (p.Arg652Gly) single nucleotide variant Benign rs2230028 GRCh37 Chromosome 7, 87056176: 87056176
25 ABCB4 NM_018849.2(ABCB4): c.3629C> G (p.Ser1210Ter) single nucleotide variant Pathogenic rs748842753 GRCh37 Chromosome 7, 87032476: 87032476
26 ABCB4 NM_018849.2(ABCB4): c.3629C> G (p.Ser1210Ter) single nucleotide variant Pathogenic rs748842753 GRCh38 Chromosome 7, 87403160: 87403160
27 ABCB4 NM_018849.2(ABCB4): c.217C> G (p.Leu73Val) single nucleotide variant Uncertain significance rs8187788 GRCh37 Chromosome 7, 87092143: 87092143
28 ABCB4 NM_018849.2(ABCB4): c.217C> G (p.Leu73Val) single nucleotide variant Uncertain significance rs8187788 GRCh38 Chromosome 7, 87462827: 87462827
29 ABCB4 NM_018849.2(ABCB4): c.3081+1G> C single nucleotide variant Pathogenic rs750829010 GRCh37 Chromosome 7, 87038551: 87038551
30 ABCB4 NM_018849.2(ABCB4): c.3081+1G> C single nucleotide variant Pathogenic rs750829010 GRCh38 Chromosome 7, 87409235: 87409235
31 ABCB4 NM_018849.2(ABCB4): c.1006-1G> T single nucleotide variant Pathogenic rs772823352 GRCh37 Chromosome 7, 87074292: 87074292
32 ABCB4 NM_018849.2(ABCB4): c.1006-1G> T single nucleotide variant Pathogenic rs772823352 GRCh38 Chromosome 7, 87444976: 87444976
33 ABCB4 NM_018849.2(ABCB4): c.3136C> T (p.Arg1046Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 7, 87037496: 87037496
34 ABCB4 NM_018849.2(ABCB4): c.3136C> T (p.Arg1046Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 7, 87408180: 87408180

Expression for Cholestasis, Progressive Familial Intrahepatic, 3

Search GEO for disease gene expression data for Cholestasis, Progressive Familial Intrahepatic, 3.

Pathways for Cholestasis, Progressive Familial Intrahepatic, 3

Pathways related to Cholestasis, Progressive Familial Intrahepatic, 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.35 ABCB11 ABCB4
2 11.01 ABCB11 ABCB4
3 10.5 ABCB11 ABCB4
4 9.9 ABCB11 ABCB4

GO Terms for Cholestasis, Progressive Familial Intrahepatic, 3

Cellular components related to Cholestasis, Progressive Familial Intrahepatic, 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 9.63 ABCB11 ABCB4 ATP11C ATP8B1 JAG1 NDUFB3
2 integral component of plasma membrane GO:0005887 9.56 ABCB11 ABCB4 ATP8B1 JAG1
3 apical part of cell GO:0045177 9.32 ABCB11 JAG1
4 apical plasma membrane GO:0016324 9.13 ABCB4 ATP8B1 JAG1
5 intercellular canaliculus GO:0046581 8.62 ABCB11 ABCB4

Biological processes related to Cholestasis, Progressive Familial Intrahepatic, 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phospholipid transport GO:0015914 9.32 ATP11C ATP8B1
2 bile acid and bile salt transport GO:0015721 9.26 ABCB11 ATP8B1
3 lipid transport GO:0006869 9.13 ABCB4 ATP11C ATP8B1
4 drug transmembrane transport GO:0006855 8.85 ATP8B1
5 phospholipid translocation GO:0045332 8.8 ABCB4 ATP11C ATP8B1

Molecular functions related to Cholestasis, Progressive Familial Intrahepatic, 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.46 ABCB11 ABCB4 ATP11C ATP8B1
2 ATPase activity, coupled to transmembrane movement of substances GO:0042626 8.96 ABCB11 ABCB4
3 phospholipid-translocating ATPase activity GO:0004012 8.62 ATP11C ATP8B1

Sources for Cholestasis, Progressive Familial Intrahepatic, 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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