MCID: CHL137
MIFTS: 47

Cholestasis, Progressive Familial Intrahepatic, 3

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

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic, 3

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

Name: Cholestasis, Progressive Familial Intrahepatic, 3 57 75
Pfic3 57 53 59 75 55
Cholestasis, Progressive Familial Intrahepatic 3 57 76 13 73
Mdr3 Deficiency 57 53 75
Progressive Familial Intrahepatic Cholestasis with Elevated Serum Gamma-Glutamyltransferase 53 75
Progressive Familial Intrahepatic Cholestasis Type 3 53 59
Progressive Familial Intrahepatic Cholestasis 3 29 6
Cholestasis, Progressive Familial Intrahepatic, with Elevated Serum Gamma-Glutamyltransferase 57
Cholestasis, Intrahepatic, Familial, Progressive, Type 3 40

Characteristics:

Orphanet epidemiological data:

59
progressive familial intrahepatic cholestasis type 3
Inheritance: Autosomal recessive; Age of onset: All ages;

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
cholestasis, progressive familial intrahepatic, 3:
Onset and clinical course infantile onset
Inheritance heterogeneous autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 602347
Orphanet 59 ORPHA79305
MESH via Orphanet 45 C535935
UMLS via Orphanet 74 C1865643
ICD10 via Orphanet 34 K76.8
MedGen 42 C1865643
MeSH 44 D002780
UMLS 73 C1865643

Summaries for Cholestasis, Progressive Familial Intrahepatic, 3

NIH Rare Diseases : 53 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 diarrhea, icterus and pruritus. 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 Bile Acids and Salts and Gastrointestinal Agents have been mentioned in the context of this disorder. Affiliated tissues include liver, spleen and testes, and related phenotypes are splenomegaly and hepatomegaly

UniProtKB/Swiss-Prot : 75 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 : 76 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

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

Symptoms via clinical synopsis from OMIM:

57
AbdomenSpleen:
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

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

32 (show all 11)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 32 HP:0001744
2 hepatomegaly 32 HP:0002240
3 malabsorption 32 HP:0002024
4 pruritus 32 HP:0000989
5 elevated hepatic transaminases 32 HP:0002910
6 cirrhosis 32 HP:0001394
7 jaundice 32 HP:0000952
8 diarrhea 32 HP:0002014
9 intrahepatic cholestasis 32 HP:0001406
10 bile duct proliferation 32 HP:0001408
11 portal fibrosis 32 HP:0006580

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


diarrhea, icterus, pruritus

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 9.5 ATP8B1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-14 9.5 ABCB11
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.5 ATP8B1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-179 9.5 ATP8B1 ABCB11
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.5 ATP8B1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-75 9.5 ABCB11
7 Decreased vaccinia virus (VACV-LREV ) gene expression GR00351-A-2 8.62 ATP8B1 JAG1

MGI Mouse Phenotypes related to Cholestasis, Progressive Familial Intrahepatic, 3:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.26 ABCB4 ATP8B1 JAG1 ABCB11
2 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 Bile Acids and Salts Not Applicable
2 Gastrointestinal Agents Not Applicable
3 Lecithin Nutraceutical 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

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 29 ABCB4

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic, 3

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

41
Liver, Spleen, Testes

Publications for Cholestasis, Progressive Familial Intrahepatic, 3

Articles related to Cholestasis, Progressive Familial Intrahepatic, 3:

(show all 16)
# Title Authors Year
1
Liver transplantation for decompensated liver cirrhosis caused by progressive familial intrahepatic cholestasis type 3: A case report. ( 29390323 )
2017
2
Molecular characterization of exons 6, 8 and 9 of ABCB4 gene in children with Progressive Familial Intrahepatic Cholestasis type 3. ( 27075526 )
2016
3
Functional characterization of ABCB4 mutations found in progressive familial intrahepatic cholestasis type 3. ( 27256251 )
2016
4
Presentation of Progressive Familial Intrahepatic Cholestasis Type 3 Mimicking Wilson Disease: Molecular Genetic Diagnosis and Response to Treatment. ( 26473142 )
2015
5
Novel mutation in a Chinese patient with progressive familial intrahepatic cholestasis type 3. ( 25593501 )
2015
6
A functional classification of ABCB4 variations causing progressive familial intrahepatic cholestasis type 3. ( 26474921 )
2015
7
Functional analysis of ABCB4 mutations relates clinical outcomes of progressive familial intrahepatic cholestasis type 3 to the degree of MDR3 floppase activity. ( 24594635 )
2014
8
Clinical utility gene card for: Progressive familial intrahepatic cholestasis type 3. ( 24002166 )
2013
9
The histidine-loop is essential for transport activity of human MDR3. A novel mutation of MDR3 in a patient with progressive familial intrahepatic cholestasis type 3. ( 22766396 )
2012
10
Progressive familial intrahepatic cholestasis type 3: overlapping presentation with Wilson disease. ( 22669981 )
2012
11
Clinical features and genotype-phenotype correlations in children with progressive familial intrahepatic cholestasis type 3 related to ABCB4 mutations. ( 21119540 )
2011
12
Two novel mutations in African and Asian children with progressive familial intrahepatic cholestasis type 3. ( 21514256 )
2011
13
A missense mutation in ABCB4 gene involved in progressive familial intrahepatic cholestasis type 3 leads to a folding defect that can be rescued by low temperature. ( 19185004 )
2009
14
Turning over or turning around: hepatic phosphatidylcholine in the mouse model for progressive familial intrahepatic cholestasis type 3. ( 18783539 )
2008
15
Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3). ( 17726488 )
2007
16
Progressive familial intrahepatic cholestasis type 3 revealed by oral contraceptive pills. ( 12713886 )
2003

Variations for Cholestasis, Progressive Familial Intrahepatic, 3

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

75 (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
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
13 ABCB4 p.Gly70Arg VAR_073732
14 ABCB4 p.Leu73Val VAR_073734 rs8187788
15 ABCB4 p.Gly126Glu VAR_073738 rs1021988376Cholestasis,
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
25 ABCB4 p.Leu481Arg VAR_073751
26 ABCB4 p.Ala511Thr VAR_073753
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 rs1051861187Cholestasis,
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 40)
# 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_018849.2(ABCB4): c.2169dupG (p.Leu724Alafs) duplication Pathogenic rs387906529 GRCh37 Chromosome 7, 87053264: 87053264
8 ABCB4 NM_018849.2(ABCB4): c.2169dupG (p.Leu724Alafs) duplication Pathogenic rs387906529 GRCh38 Chromosome 7, 87423948: 87423948
9 ABCB4 NM_018849.2(ABCB4): c.1207T> C (p.Tyr403His) single nucleotide variant Pathogenic rs121918443 GRCh37 Chromosome 7, 87073002: 87073002
10 ABCB4 NM_018849.2(ABCB4): c.1207T> C (p.Tyr403His) single nucleotide variant Pathogenic rs121918443 GRCh38 Chromosome 7, 87443686: 87443686
11 ABCB4 NM_018849.2(ABCB4): c.2906G> A (p.Arg969His) single nucleotide variant Uncertain significance rs752916287 GRCh37 Chromosome 7, 87041227: 87041227
12 ABCB4 NM_018849.2(ABCB4): c.2906G> A (p.Arg969His) single nucleotide variant Uncertain significance rs752916287 GRCh38 Chromosome 7, 87411911: 87411911
13 ABCB4 NM_018849.2(ABCB4): c.2211+1G> A single nucleotide variant Pathogenic rs794727183 GRCh37 Chromosome 7, 87053221: 87053221
14 ABCB4 NM_018849.2(ABCB4): c.2211+1G> A single nucleotide variant Pathogenic rs794727183 GRCh38 Chromosome 7, 87423905: 87423905
15 ABCB4 NM_018849.2(ABCB4): c.2177C> T (p.Pro726Leu) single nucleotide variant Likely pathogenic rs141677867 GRCh37 Chromosome 7, 87053256: 87053256
16 ABCB4 NM_018849.2(ABCB4): c.2177C> T (p.Pro726Leu) single nucleotide variant Likely pathogenic rs141677867 GRCh38 Chromosome 7, 87423940: 87423940
17 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
18 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
19 ABCB4 NM_018849.2(ABCB4): c.431G> A (p.Arg144Gln) single nucleotide variant no interpretation for the single variant rs863225299 GRCh37 Chromosome 7, 87082365: 87082365
20 ABCB4 NM_018849.2(ABCB4): c.431G> A (p.Arg144Gln) single nucleotide variant no interpretation for the single variant rs863225299 GRCh38 Chromosome 7, 87453049: 87453049
21 ABCB4 NM_018849.2(ABCB4): c.2833C> T (p.Gln945Ter) single nucleotide variant Pathogenic rs886042562 GRCh37 Chromosome 7, 87041300: 87041300
22 ABCB4 NM_018849.2(ABCB4): c.2833C> T (p.Gln945Ter) single nucleotide variant Pathogenic rs886042562 GRCh38 Chromosome 7, 87411984: 87411984
23 ABCB4 NM_018849.2(ABCB4): c.3629C> G (p.Ser1210Ter) single nucleotide variant Pathogenic rs748842753 GRCh37 Chromosome 7, 87032476: 87032476
24 ABCB4 NM_018849.2(ABCB4): c.3629C> G (p.Ser1210Ter) single nucleotide variant Pathogenic rs748842753 GRCh38 Chromosome 7, 87403160: 87403160
25 ABCB4 NM_018849.2(ABCB4): c.2626A> T (p.Lys876Ter) single nucleotide variant Pathogenic rs886043725 GRCh37 Chromosome 7, 87046684: 87046684
26 ABCB4 NM_018849.2(ABCB4): c.2626A> T (p.Lys876Ter) single nucleotide variant Pathogenic rs886043725 GRCh38 Chromosome 7, 87417368: 87417368
27 ABCB4 NM_018849.2(ABCB4): c.2625_2626delGAinsAT (p.Met875_Lys876delinsIleTer) indel Pathogenic rs886043734 GRCh37 Chromosome 7, 87046684: 87046685
28 ABCB4 NM_018849.2(ABCB4): c.2625_2626delGAinsAT (p.Met875_Lys876delinsIleTer) indel Pathogenic rs886043734 GRCh38 Chromosome 7, 87417368: 87417369
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.1144G> T (p.Glu382Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 7, 87073065: 87073065
32 ABCB4 NM_018849.2(ABCB4): c.1144G> T (p.Glu382Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 7, 87443749: 87443749
33 ABCB4 NM_018849.2(ABCB4): c.1006-1G> T single nucleotide variant Pathogenic rs772823352 GRCh37 Chromosome 7, 87074292: 87074292
34 ABCB4 NM_018849.2(ABCB4): c.1006-1G> T single nucleotide variant Pathogenic rs772823352 GRCh38 Chromosome 7, 87444976: 87444976
35 ABCB4 NM_018849.2(ABCB4): c.2446delA (p.Arg816Aspfs) deletion Pathogenic GRCh37 Chromosome 7, 87047885: 87047885
36 ABCB4 NM_018849.2(ABCB4): c.2446delA (p.Arg816Aspfs) deletion Pathogenic GRCh38 Chromosome 7, 87418569: 87418569
37 ABCB4 NM_018849.2(ABCB4): c.100delAinsAA (p.Thr34Asnfs) indel Pathogenic GRCh37 Chromosome 7, 87101972: 87101972
38 ABCB4 NM_018849.2(ABCB4): c.100delAinsAA (p.Thr34Asnfs) indel Pathogenic GRCh38 Chromosome 7, 87472656: 87472656
39 ABCB4 NM_018849.2(ABCB4): c.139C> T (p.Arg47Ter) single nucleotide variant Pathogenic rs376926391 GRCh37 Chromosome 7, 87092221: 87092221
40 ABCB4 NM_018849.2(ABCB4): c.139C> T (p.Arg47Ter) single nucleotide variant Pathogenic rs376926391 GRCh38 Chromosome 7, 87462905: 87462905

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 plasma membrane GO:0005887 9.56 ABCB11 ABCB4 ATP8B1 JAG1
2 apical plasma membrane GO:0016324 9.33 ABCB4 ATP8B1 JAG1
3 brush border membrane GO:0031526 9.32 ABCB4 ATP8B1
4 intercellular canaliculus GO:0046581 8.96 ABCB11 ABCB4
5 apical part of cell GO:0045177 8.8 ABCB11 ABCB4 JAG1

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

# Name GO ID Score Top Affiliating Genes
1 lipid transport GO:0006869 9.26 ABCB4 ATP8B1
2 bile acid and bile salt transport GO:0015721 9.16 ABCB11 ATP8B1
3 drug transmembrane transport GO:0006855 8.96 ABCB4 ATP8B1
4 phospholipid translocation GO:0045332 8.62 ABCB4 ATP8B1

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

# Name GO ID Score Top Affiliating Genes
1 ATPase activity GO:0016887 8.96 ABCB11 ABCB4
2 ATPase activity, coupled to transmembrane movement of substances GO:0042626 8.62 ABCB11 ABCB4

Sources for Cholestasis, Progressive Familial Intrahepatic, 3

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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