MCID: CHL082
MIFTS: 44

Cholestasis, Progressive Familial Intrahepatic 3

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

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic 3

MalaCards integrated aliases for Cholestasis, Progressive Familial Intrahepatic 3:

Name: Cholestasis, Progressive Familial Intrahepatic 3 54 13 69
Pfic3 50 24 56 71 52
Progressive Familial Intrahepatic Cholestasis with Elevated Serum Gamma-Glutamyltransferase 50 71
Progressive Familial Intrahepatic Cholestasis Type 3 50 56
Progressive Familial Intrahepatic Cholestasis 3 24 29
Mdr3 Deficiency 50 71
Cholestasis, Progressive Familial Intrahepatic, 3 71
Pfic 3 24

Characteristics:

Orphanet epidemiological data:

56
progressive familial intrahepatic cholestasis type 3
Inheritance: Autosomal recessive; Age of onset: All ages;

OMIM:

54
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 54 602347
Orphanet 56 ORPHA79305
MESH via Orphanet 43 C535935
UMLS via Orphanet 70 C1865643
ICD10 via Orphanet 34 K76.8
MedGen 40 C1865643
MeSH 42 D002780

Summaries for Cholestasis, Progressive Familial Intrahepatic 3

NIH Rare Diseases : 50 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. last updated: 11/4/2015

MalaCards based summary : Cholestasis, Progressive Familial Intrahepatic 3, also known as pfic3, is related to cholestasis, progressive familial intrahepatic 1 and gallbladder disease 1, and has symptoms including diarrhea, hepatomegaly and splenomegaly. 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 Decreased shRNA abundance (Z-score < -2) and liver/biliary system

UniProtKB/Swiss-Prot : 71 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.

Description from OMIM: 602347

Related Diseases for Cholestasis, Progressive Familial Intrahepatic 3

Diseases in the Intrahepatic Cholestasis family:

Cholestasis, Progressive Familial Intrahepatic 2 Cholestasis, Benign Recurrent Intrahepatic, 2
Cholestasis, Progressive Familial Intrahepatic 3 Cholestasis, Progressive Familial Intrahepatic 4
Cholestasis, Progressive Familial Intrahepatic, 5 Cholestasis, Progressive Familial Intrahepatic 1
Cholestasis, Benign Recurrent Intrahepatic Abcb11-Related Intrahepatic Cholestasis
Atp8b1-Related Intrahepatic Cholestasis 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)
id Related Disease Score Top Affiliating Genes
1 cholestasis, progressive familial intrahepatic 1 10.9
2 gallbladder disease 1 10.8
3 cholestasis 10.5
4 intrahepatic cholestasis 10.5
5 wilson disease 10.1
6 hepatitis 9.9
7 alport syndrome and thin basement membrane nephropathy 9.5 ABCB11 ATP8B1
8 isthmus cancer 9.5 ABCB11 ABCB4
9 cholestasis, intrahepatic, of pregnancy, 1 9.5 ABCB11 ATP8B1
10 acute cholangitis 9.4 ABCB11 ABCB4
11 patent foramen ovale 9.2 ABCB11 JAG1
12 cholestasis, benign recurrent intrahepatic, 2 9.1 ABCB11 ABCB4 ATP8B1
13 orbital cancer 9.1 ABCB11 ABCB4 ATP8B1
14 hemorrhoid 9.0 ABCB11 ABCB4 ATP8B1
15 lymphoblastic lymphoma 8.9 ABCB11 ABCB4 ATP8B1
16 cholestasis, intrahepatic, of pregnancy, 3 8.6 ABCB11 ABCB4 ATP8B1 JAG1
17 cholestasis, benign recurrent intrahepatic 8.6 ABCB11 ABCB4 ATP8B1 JAG1
18 bardet-biedl syndrome 6 8.6 ABCB11 ABCB4 ATP8B1 JAG1
19 chronic rheumatic pericarditis 8.6 ABCB11 ABCB4 ATP8B1 JAG1
20 eclampsia 8.6 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

Symptoms via clinical synopsis from OMIM:

54

Abdomen- Gastroin testinal:
diarrhea
malabsorption of fat and fat-soluble vitamins

Abdomen- Spleen:
splenomegaly

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

Abdomen- Liver:
hepatomegaly
jaundice
cirrhosis
intrahepatic cholestasis
end-stage liver disease before adulthood
more
Skin Nails & Hair- Skin:
jaundice
pruritus


Clinical features from OMIM:

602347

Human phenotypes related to Cholestasis, Progressive Familial Intrahepatic 3:

32 (show all 11)
id Description HPO Frequency HPO Source Accession
1 diarrhea 32 HP:0002014
2 hepatomegaly 32 HP:0002240
3 splenomegaly 32 HP:0001744
4 jaundice 32 HP:0000952
5 cirrhosis 32 HP:0001394
6 malabsorption 32 HP:0002024
7 intrahepatic cholestasis 32 HP:0001406
8 pruritus 32 HP:0000989
9 bile duct proliferation 32 HP:0001408
10 elevated hepatic transaminases 32 HP:0002910
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
id 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 ABCB11 ATP8B1
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:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 liver/biliary system MP:0005370 8.92 ATP8B1 JAG1 ABCB11 ABCB4

Drugs & Therapeutics for Cholestasis, Progressive Familial Intrahepatic 3

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


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Bile Acids and Salts
2 Gastrointestinal Agents
3 Lecithin Nutraceutical

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Second-line Therapy of Unresectable Cholangiocarcinoma by RADIOEMBOLIZATION Terminated NCT01383746 Phase 1, Phase 2
2 An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects Completed NCT03082937 Phase 1 3 mg [14C]-A4250 capsule
3 Intralumenal Effects on Cholesterol Absorption/Synthesis Completed NCT00328211 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:

id Genetic test Affiliating Genes
1 Progressive Familial Intrahepatic Cholestasis 3 29 24 ABCB4

Anatomical Context for Cholestasis, Progressive Familial Intrahepatic 3

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

39
Liver, Spleen, Testes

Publications for Cholestasis, Progressive Familial Intrahepatic 3

Variations for Cholestasis, Progressive Familial Intrahepatic 3

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

71 (show all 39)
id 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
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
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
38 ABCB4 p.Glu1125Lys VAR_073776
39 ABCB4 p.Ala1193Thr VAR_073777

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

6
id 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.2869C> T (p.Arg957Ter) single nucleotide variant Pathogenic rs121918440 GRCh37 Chromosome 7, 87041264: 87041264
3 ABCB4 NM_018849.2(ABCB4): c.1712delT (p.Val571Aspfs) deletion Pathogenic rs387906527 GRCh37 Chromosome 7, 87069002: 87069002
4 ABCB4 NM_018849.2(ABCB4): c.2169dupG (p.Leu724Alafs) duplication Pathogenic rs387906529 GRCh37 Chromosome 7, 87053264: 87053264
5 ABCB4 NM_018849.2(ABCB4): c.1207T> C (p.Tyr403His) single nucleotide variant Pathogenic rs121918443 GRCh37 Chromosome 7, 87073002: 87073002
6 ABCB4 NM_018849.2(ABCB4): c.2211+1G> A single nucleotide variant Pathogenic rs794727183 GRCh37 Chromosome 7, 87053221: 87053221
7 ABCB4 NM_018849.2(ABCB4): c.2833C> T (p.Gln945Ter) single nucleotide variant Pathogenic rs886042562 GRCh37 Chromosome 7, 87041300: 87041300
8 ABCB4 NM_018849.2(ABCB4): c.2626A> T (p.Lys876Ter) single nucleotide variant Pathogenic rs886043725 GRCh37 Chromosome 7, 87046684: 87046684
9 ABCB4 NM_018849.2(ABCB4): c.2625_2626delGAinsAT (p.Met875_Lys876delinsIleTer) indel Pathogenic rs886043734 GRCh37 Chromosome 7, 87046684: 87046685

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:

id 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:

id 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:

id 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 phospholipid translocation GO:0045332 8.96 ABCB4 ATP8B1
4 drug transmembrane transport GO:0006855 8.62 ABCB4 ATP8B1

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

id 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
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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