Cholestasis, Progressive Familial Intrahepatic, 3 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

PFIC3 MCID: CHL137 MIFTS: 51	Cholestasis, Progressive Familial Intrahepatic, 3 (PFIC3) Categories: Cancer diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Rare diseases
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Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic, 3

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

Name: Cholestasis, Progressive Familial Intrahepatic, 3 ⁵⁶ ⁷³

Pfic3 ⁵⁶ ¹² ⁵² ⁵⁸ ⁷³ ⁵⁴

Cholestasis, Progressive Familial Intrahepatic 3 ⁵⁶ ⁷⁴ ¹³ ⁴³ ⁷¹

Progressive Familial Intrahepatic Cholestasis 3 ¹² ²⁹ ⁶ ¹⁵

Mdr3 Deficiency ⁵⁶ ¹² ⁵² ⁷³

Progressive Familial Intrahepatic Cholestasis with Elevated Serum Gamma-Glutamyltransferase ⁵² ⁷³

Progressive Familial Intrahepatic Cholestasis Type 3 ⁵² ⁵⁸

Cholestasis, Progressive Familial Intrahepatic, with Elevated Serum Gamma-Glutamyltransferase ⁵⁶

Progressive Familial Intrahepatic Cholestasis with Elevated Serum Gama-Glutamyltransferase ¹²

Cholestasis, Intrahepatic, Familial, Progressive, Type 3 ³⁹

Characteristics:

Orphanet epidemiological data:

⁵⁸

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

OMIM:

⁵⁶

Inheritance:
autosomal recessive

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

HPO:

³¹

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

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases Cancer diseases
Anatomical: Liver diseases Gastrointestinal diseases

See all MalaCards categories (disease lists)

ICD10: ³³

Diseases of the digestive system

Diseases of liver

Other diseases of liver

Other specified diseases of liver

Orphanet: ⁵⁸

Rare hepatic diseases

Inborn errors of metabolism

External Ids:

Disease Ontology ¹² DOID:0070223

OMIM ⁵⁶ 602347

OMIM Phenotypic Series ⁵⁶ PS211600

MeSH ⁴³ C535935 D002780

MESH via Orphanet ⁴⁴ C535935

ICD10 via Orphanet ³³ K76.8

UMLS via Orphanet ⁷² C1865643

Orphanet ⁵⁸ ORPHA79305

MedGen ⁴¹ C1865643

SNOMED-CT via HPO ⁶⁸ 16294009 166603001 166643006 more

UMLS ⁷¹ C1865643

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Summaries for Cholestasis, Progressive Familial Intrahepatic, 3

NIH Rare Diseases : ⁵² 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 cholangitis and atp8b1 deficiency, 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 Synthesis of bile acids and bile salts and Hepatic ABC Transporters. The drugs Lecithin 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 : ⁷³ 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 : ⁷⁴ Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions... more...

More information from OMIM: 602347 PS211600

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Related Diseases for Cholestasis, Progressive Familial Intrahepatic, 3

Diseases in the 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	Progressive Familial 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 top 50) (show all 81)

#	Related Disease	Score	Top Affiliating Genes
1	cholangitis	30.4	NR1H4 ABCB4 ABCB11
2	atp8b1 deficiency	30.4	NR1H4 ATP8B1 ABCB11
3	progressive familial intrahepatic cholestasis	29.7	TJP2 SLC10A2 SLC10A1 NR1H4 ATP8B1 ABCG8
4	cholelithiasis	29.4	NR1H4 ABCG8 ABCG5 ABCB4
5	intrahepatic cholestasis of pregnancy	29.4	NR1H4 ATP8B1 ABCC2 ABCB4 ABCB11
6	cholestasis, benign recurrent intrahepatic, 1	29.3	TJP2 SLC10A2 SLC10A1 NR1H4 ATP8B1 ABCG8
7	familial intrahepatic cholestasis	29.1	TJP2 SLC10A2 NR1H4 ATP8B1 ABCC2 ABCB4
8	cholestasis, intrahepatic, of pregnancy, 1	29.0	SLC10A2 NR1H4 JAG1 ATP8B1 ABCC2 ABCB4
9	biliary atresia	29.0	SLC10A2 SLC10A1 NR1H4 JAG1 ATP8B1 ABCB4
10	cholestasis	28.3	TJP2 SLC10A2 SLC10A1 NR1H4 JAG1 ATP8B1
11	cholestasis, progressive familial intrahepatic, 1	28.1	TJP2 SLC10A2 SLC10A1 NR1H4 JAG1 GGTLC3
12	gallbladder disease 1	11.2
13	autosomal dominant non-syndromic intellectual disability 3	10.4	ABCB4 ABCB11
14	autosomal recessive disease	10.3
15	chronic cholangitis	10.3	ATP8B1 ABCB4
16	wilson disease	10.3
17	caroli disease	10.2	ATP8B1 ABCB4
18	functional diarrhea	10.2	SLC10A2 NR1H4
19	portal hypertension	10.1
20	hepatocellular carcinoma	10.1
21	cholecystitis	10.1
22	liver cirrhosis	10.1
23	splenomegaly	10.1
24	posttransplant acute limbic encephalitis	10.1
25	dubin-johnson syndrome	10.0	ATP8B1 ABCC2 ABCB11
26	sitosterolemia 2	10.0	ABCG8 ABCG5
27	bile acid synthesis defect, congenital, 2	10.0	SLC10A1 NR1H4 ABCB11
28	gallbladder disease 4	10.0	ABCG8 ABCG5
29	sitosterolemia 1	10.0	ABCG8 ABCG5
30	urea cycle disorder	10.0	ATP8B1 ABCB11
31	alagille syndrome 1	10.0	JAG1 ATP8B1 ABCB4 ABCB11
32	homozygous familial hypercholesterolemia	9.9	ABCG8 ABCG5
33	pericholangitis	9.9	SLC10A2 SLC10A1 ABCB4 ABCB11
34	sclerosing cholangitis	9.8	NR1H4 ABCC2 ABCB4 ABCB11
35	bile duct rhabdomyosarcoma	9.8	GGTLC3 GGT2
36	hypercholesterolemia, familial, 1	9.8	NR1H4 ABCG8 ABCG5
37	bile duct sarcoma	9.8	GGTLC3 GGT2
38	splenic tuberculosis	9.8	GGTLC3 GGT2
39	gallbladder papillary carcinoma	9.8	GGTLC3 GGT2
40	extrahepatic bile duct adenoma	9.8	GGTLC3 GGT2
41	cholestasis, progressive familial intrahepatic, 5	9.8	TJP2 NR1H4 ATP8B1 ABCB11
42	optic nerve astrocytoma	9.8	GGTLC3 GGT2
43	ascending cholangitis	9.7	GGTLC3 GGT2
44	myasthenic syndrome, congenital, 3b, fast-channel	9.7	GGTLC3 GGT2
45	dientamoebiasis	9.7	GGTLC3 GGT2
46	algoneurodystrophy	9.7	GGTLC3 GGT2
47	giant axonal neuropathy 1, autosomal recessive	9.7	GGTLC3 GGT2
48	acute cholangitis	9.7	GGTLC3 GGT2
49	amelogenesis imperfecta, type if	9.7	GGTLC3 GGT2
50	retinitis pigmentosa 48	9.7	GGTLC3 GGT2

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

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Symptoms & Phenotypes for Cholestasis, Progressive Familial Intrahepatic, 3

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

³¹ (show all 11)

#	Description	HPO Source Accession
1	splenomegaly ³¹	HP:0001744
2	hepatomegaly ³¹	HP:0002240
3	malabsorption ³¹	HP:0002024
4	pruritus ³¹	HP:0000989
5	cirrhosis ³¹	HP:0001394
6	elevated hepatic transaminase ³¹	HP:0002910
7	jaundice ³¹	HP:0000952
8	diarrhea ³¹	HP:0002014
9	intrahepatic cholestasis ³¹	HP:0001406
10	portal fibrosis ³¹	HP:0006580
11	bile duct proliferation ³¹	HP:0001408

Symptoms via clinical synopsis from OMIM:

⁵⁶

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:

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, 3:

⁴⁵

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	digestive/alimentary	MP:0005381	9.63	ABCB4 ABCG5 ABCG8 JAG1 NR1H4 SLC10A2
2	homeostasis/metabolism	MP:0005376	9.61	ABCB11 ABCB4 ABCC2 ABCG5 ABCG8 ATP8B1
3	liver/biliary system	MP:0005370	9.28	ABCB11 ABCB4 ABCC2 ABCG5 ABCG8 ATP8B1

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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	Lecithin
2	Bile Acids and Salts
3	Gastrointestinal Agents

Interventional clinical trials:

#	Name	Status	NCT ID	Phase	Drugs
1	Efficacy and Tolerance of RADIOEMBOLIZATION for Patients With Unresectable Intrahepatic Cholangiocarcinoma With Tumor Progression After First-line Therapy	Terminated	NCT01383746	Phase 1, Phase 2
2	Intralumenal Effects on Cholesterol Absorption/Synthesis	Completed	NCT00328211		Pluronic F-68

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

Cochrane evidence based reviews: cholestasis, progressive familial intrahepatic 3

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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

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Anatomical Context for Cholestasis, Progressive Familial Intrahepatic, 3

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

⁴⁰

Liver, Spleen, Testes

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Publications for Cholestasis, Progressive Familial Intrahepatic, 3

Articles related to Cholestasis, Progressive Familial Intrahepatic, 3:

(show top 50) (show all 56)

#	Title	Authors	PMID	Year
1	Heterozygous non-sense mutation of the MDR3 gene in familial intrahepatic cholestasis of pregnancy. ⁵⁶ ⁶	Jacquemin E...Hadchouel M	9923886	1999
2	Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. ⁵⁶ ⁶	de Vree JM...Hadchouel M	9419367	1998
3	Defect of multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis. ⁵⁶ ⁶	Deleuze JF...Hadchouel M	8666348	1996
4	Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3). ⁵⁴ ⁶¹ ⁵⁶	Degiorgio D...Coviello DA	17726488	2007
5	DHPLC screening for mutations in progressive familial intrahepatic cholestasis patients. ⁵⁴ ⁶¹	Shapiro R...Bercovich D	20414253	2010
6	The spectrum of liver diseases related to ABCB4 gene mutations: pathophysiology and clinical aspects. ⁵⁴ ⁶¹	Davit-Spraul A...Jacquemin E	20422496	2010
7	Combined features of low phospholipid-associated cholelithiasis and progressive familial intrahepatic cholestasis 3. ⁵⁴ ⁶¹	Poupon R...Housset C	19840255	2010
8	[Genetic cholestasis]. ⁵⁴ ⁶¹	Ciocca M...Alvarez F	19753442	2009
9	Progressive familial intrahepatic cholestasis. ⁵⁴ ⁶¹	Davit-Spraul A...Jacquemin E	19133130	2009
10	Novel resequencing chip customized to diagnose mutations in patients with inherited syndromes of intrahepatic cholestasis. ⁵⁴ ⁶¹	Liu C...Bezerra JA	17241866	2007
11	Genetic variability, haplotype structures, and ethnic diversity of hepatic transporters MDR3 (ABCB4) and bile salt export pump (ABCB11). ⁵⁴ ⁶¹	Lang T...Kerb R	16763017	2006
12	Effect of mdr2 mutation with combined tandem disruption of canalicular glycoprotein transporters by cyclosporine A on bile formation in mice. ⁵⁴ ⁶¹	Elamiri A...Yousef IM	12967592	2003
13	Role of multidrug resistance 3 deficiency in pediatric and adult liver disease: one gene for three diseases. ⁵⁴ ⁶¹	Jacquemin E	11745043	2001
14	Gene therapy for progressive familial intrahepatic cholestasis type 3 in a clinically relevant mouse model. ⁶¹	Weber ND...Smerdou C	31836711	2019
15	Prevention of Cholestatic Liver Disease and Reduced Tumorigenicity in a Murine Model of PFIC Type 3 Using Hybrid AAV-piggyBac Gene Therapy. ⁶¹	Siew SM...Alexander IE	31099022	2019
16	ABCB4 disease mimicking morbus Wilson: A potential diagnostic pitfall. ⁶¹	Sticova E...Jirsa M	31728073	2019
17	Progressive familial intrahepatic cholestasis type-3 and multiple sclerosis: lessons from comorbidity. ⁶¹	De Masi R...De Donno A	31568708	2019
18	Familial intrahepatic cholestasis: New and wide perspectives. ⁶¹	Vitale G...Andreone P	31105019	2019
19	Liver-directed gene therapy results in long-term correction of progressive familial intrahepatic cholestasis type 3 in mice. ⁶¹	Aronson SJ...Bosma PJ	30935993	2019
20	Biliary atresia combined with progressive familial intrahepatic cholestasis type 3: A case report and review of the literature. ⁶¹	Zhang BP...Dong C	31083246	2019
21	Structural analogues of roscovitine rescue the intracellular traffic and the function of ER-retained ABCB4 variants in cell models. ⁶¹	Vauthier V...Falguieres T	31040306	2019
22	Hydrophilic bile acids prevent liver damage caused by lack of biliary phospholipid in Mdr2-/- mice. ⁶¹	Wang R...Ling V	30416103	2019
23	Phenotypic variability in Tunisian PFIC3 patients harboring a complex genotype with a differential clinical outcome of UDCA treatment. ⁶¹	Khabou B...Fakhfakh F	30036524	2018
24	ABCB4 Gene Aberrations in Human Liver Disease: An Evolving Spectrum. ⁶¹	Reichert MC...Lammert F	30357767	2018
25	Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases. ⁶¹	Chen HL...Chang MH	30367658	2018
26	Liver Transplantation for Progressive Familial Intrahepatic Cholestasis. ⁶¹	Liu Y...Zeng ZG	30250015	2018
27	Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset. ⁶¹	Schatz SB...Baumann U	29761167	2018
28	Current and future therapies for inherited cholestatic liver diseases. ⁶¹	van der Woerd WL...van de Graaf SF	28223721	2017
29	Functional defect of variants in the adenosine triphosphate-binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770). ⁶¹	Delaunay JL...Ait-Slimane T	28012258	2017
30	A New Mutation Causing Progressive Familiar Intrahepatic Cholestasis Type 3 in Association with Autoimmune Hepatitis. ⁶¹	Oliveira HM...Pessegueiro-Miranda H	30755924	2017
31	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. ⁶¹	Khabou B...Fakhfakh F	27788395	2016
32	Molecular characterization of exons 6, 8 and 9 of ABCB4 gene in children with Progressive Familial Intrahepatic Cholestasis type 3. ⁶¹	Fathy M...Hassan N	27075526	2016
33	Functional characterization of ABCB4 mutations found in progressive familial intrahepatic cholestasis type 3. ⁶¹	Park HJ...Choi JH	27256251	2016
34	ABCB4 mutations in adult patients with cholestatic liver disease: impact and phenotypic expression. ⁶¹	Degiorgio D...Battezzati PM	26324191	2016
35	Hepatic immunohistochemistry of bile transporters in progressive familial intrahepatic cholestasis. ⁶¹	El-Guindi MA...Elsheikh NM	26845599	2016
36	Hepatic immunohistochemistry of bile transporters in progressive familial intrahepatic cholestasis. ⁶¹	El-Guindi MA...Elsheikh NM	31196404	2016
37	Presentation of Progressive Familial Intrahepatic Cholestasis Type 3 Mimicking Wilson Disease: Molecular Genetic Diagnosis and Response to Treatment. ⁶¹	Boga S...Schilsky ML	26473142	2015
38	Elevated copper impairs hepatic nuclear receptor function in Wilson's disease. ⁶¹	Wooton-Kee CR...Moore DD	26241054	2015
39	Novel mutation in a Chinese patient with progressive familial intrahepatic cholestasis type 3. ⁶¹	Sun HZ...Shen XZ	25593501	2015
40	Functional analysis of ABCB4 mutations relates clinical outcomes of progressive familial intrahepatic cholestasis type 3 to the degree of MDR3 floppase activity. ⁶¹	Gordo-Gilart R...Alvarez L	24594635	2015
41	Phospholipid flippase activities and substrate specificities of human type IV P-type ATPases localized to the plasma membrane. ⁶¹	Takatsu H...Shin HW	25315773	2014
42	Hepatic cytochrome P450 deficiency in mouse models for intrahepatic cholestasis predispose to bile salt-induced cholestasis. ⁶¹	Kunne C...Paulusma CC	25068656	2014
43	ABCB4: Insights from pathobiology into therapy. ⁶¹	Falguieres T...Maurice M	24953525	2014
44	Progressive familial intrahepatic cholestasis. ⁶¹	Srivastava A	25755532	2014
45	Progressive familial intrahepatic cholestasis. ⁶¹	Jacquemin E	23141890	2012
46	Hepatobiliary transport in health and disease. ⁶¹	Chan J...Vandeberg JL	22859919	2012
47	First description of ABCB4 gene deletions in familial low phospholipid-associated cholelithiasis and oral contraceptives-induced cholestasis. ⁶¹	Pasmant E...Parfait B	21989363	2012
48	Canalicular ABC transporters and liver disease. ⁶¹	Nicolaou M...Linton KJ	21984474	2012
49	Liver disease associated with canalicular transport defects: current and future therapies. ⁶¹	Stapelbroek JM...Houwen RH	20034695	2010
50	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. ⁶¹	Delaunay JL...Maurice M	19185004	2009

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Genes for Cholestasis, Progressive Familial Intrahepatic, 3

Genes related to Cholestasis, Progressive Familial Intrahepatic, 3 (1 elite genes):

(show all 13)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	ABCB4	ATP Binding Cassette Subfamily B Member 4	Protein Coding	1591.19	Molecular basis known ⁵⁶ Pathogenic ⁶ Causative germline mutation (loss of function) ⁵⁸ Causative variation ⁷³ DISEASES inferred ¹⁵ Novoseek inferred ⁵⁴ GeneCards inferred via : Disorders Variants (show sections)	8666348 9923886 9419367 (more) 11745043 17726488 20422496 19840255 12671900 12967592 20414253 17241866 16763017 14527955 19133130 10975791 19753442
2	ATP8B1	ATPase Phospholipid Transporting 8B1	Protein Coding	20.47	DISEASES inferred ¹⁵ Novoseek inferred ⁵⁴	19753442 20414253 17241866
3	ABCB11	ATP Binding Cassette Subfamily B Member 11	Protein Coding	19.35	DISEASES inferred ¹⁵ Novoseek inferred ⁵⁴	19753442 20414253 17241866
4	JAG1	Jagged Canonical Notch Ligand 1	Protein Coding	15.18	DISEASES inferred ¹⁵ Novoseek inferred ⁵⁴	17241866
5	SLC10A2	Solute Carrier Family 10 Member 2	Protein Coding	6.71	DISEASES inferred ¹⁵
6	NR1H4	Nuclear Receptor Subfamily 1 Group H Member 4	Protein Coding	6.63	DISEASES inferred ¹⁵
7	ABCG5	ATP Binding Cassette Subfamily G Member 5	Protein Coding	6.5	DISEASES inferred ¹⁵
8	SLC10A1	Solute Carrier Family 10 Member 1	Protein Coding	6.48	DISEASES inferred ¹⁵
9	ABCC2	ATP Binding Cassette Subfamily C Member 2	Protein Coding	6.28	DISEASES inferred ¹⁵
10	TJP2	Tight Junction Protein 2	Protein Coding	6.22	DISEASES inferred ¹⁵
11	ABCG8	ATP Binding Cassette Subfamily G Member 8	Protein Coding	6.14	DISEASES inferred ¹⁵
12	GGT2	Gamma-Glutamyltransferase 2	Protein Coding	6.04	DISEASES inferred ¹⁵
13	GGTLC3	Gamma-Glutamyltransferase Light Chain Family Member 3	Protein Coding	6.04	DISEASES inferred ¹⁵

Sources

Variations for Cholestasis, Progressive Familial Intrahepatic, 3

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

⁶ (show all 15) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	GRCh37 Pos	GRCh38 Pos
1	ABCB4	NM_000443.4(ABCB4):c.394_400del (p.Tyr132fs)	deletion	Pathogenic	13686	rs387906526	7:87082396-87082402	7:87453080-87453086
2	ABCB4	NM_000443.4(ABCB4):c.1712del (p.Val571fs)	deletion	Pathogenic	13688	rs387906527	7:87069002-87069002	7:87439686-87439686
3	ABCB4	NM_000443.4(ABCB4):c.2169dup (p.Leu724fs)	duplication	Pathogenic	13694	rs387906529	7:87053263-87053264	7:87423947-87423948
4	ABCB4	NM_000443.4(ABCB4):c.1207T>C (p.Tyr403His)	SNV	Pathogenic	13695	rs121918443	7:87073002-87073002	7:87443686-87443686
5	ABCB4	NM_000443.4(ABCB4):c.3136C>T (p.Arg1046Ter)	SNV	Pathogenic	587488	rs759202962	7:87037496-87037496	7:87408180-87408180
6	ABCB4	NM_000443.4(ABCB4):c.3077del (p.Lys1026fs)	deletion	Pathogenic	635317		7:87038556-87038556	7:87409240-87409240
7	ABCB4	NM_000443.4(ABCB4):c.2869C>T (p.Arg957Ter)	SNV	Likely pathogenic	13687	rs121918440	7:87041264-87041264	7:87411948-87411948
8	ABCB4	NM_000443.4(ABCB4):c.1210C>G (p.Pro404Ala)	SNV	Likely pathogenic	242455	rs863225298	7:87072999-87072999	7:87443683-87443683
9	ABCB4	NM_000443.4(ABCB4):c.101C>T (p.Thr34Met)	SNV	Conflicting interpretations of pathogenicity	196273	rs142794414	7:87101971-87101971	7:87472655-87472655
10	ABCB4	NM_000443.4(ABCB4):c.959C>T (p.Ser320Phe)	SNV	Conflicting interpretations of pathogenicity	13690	rs72552778	7:87076396-87076396	7:87447080-87447080
11	ABCB4	NM_000443.4(ABCB4):c.1769G>A (p.Arg590Gln)	SNV	Conflicting interpretations of pathogenicity	13697	rs45575636	7:87060844-87060844	7:87431528-87431528
12	ABCB4	NM_000443.4(ABCB4):c.217C>G (p.Leu73Val)	SNV	Uncertain significance	374521	rs8187788	7:87092143-87092143	7:87462827-87462827
13	ABCB4	NM_000443.4(ABCB4):c.2906G>A (p.Arg969His)	SNV	Uncertain significance	191220	rs752916287	7:87041227-87041227	7:87411911-87411911
14	ABCB4	NM_000443.4(ABCB4):c.431G>A (p.Arg144Gln)	SNV	Uncertain significance	242454	rs863225299	7:87082365-87082365	7:87453049-87453049
15	ABCB4	NM_000443.4(ABCB4):c.1954A>G (p.Arg652Gly)	SNV	Benign	256160	rs2230028	7:87056176-87056176	7:87426860-87426860

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

⁷³ (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

Sources

Expression for Cholestasis, Progressive Familial Intrahepatic, 3

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

Sources

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	Synthesis of bile acids and bile salts ⁶⁵ Show member pathways Bile acid and bile salt metabolism ⁶⁵ bile acid biosynthesis, neutral pathway ¹ Primary bile acid biosynthesis ³⁶ Recycling of bile acids and salts ⁶⁵ Synthesis of bile acids and bile salts via 24-hydroxycholesterol ⁶⁵ Synthesis of bile acids and bile salts via 27-hydroxycholesterol ⁶⁵ Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol ⁶⁵	11.91	SLC10A2 SLC10A1 NR1H4 ABCB11
2	Hepatic ABC Transporters ⁶³ Show member pathways MODY (Maturity-Onset Diabetes of Young) ⁶³	11.72	SLC10A1 ABCC2 ABCB4 ABCB11
3	Statin Pathway ¹ Show member pathways Cholesterol metabolism ³⁶ Composition of Lipid Particles ¹ Statin Pathway, Pharmacodynamics ⁶⁰	11.65	ABCG8 ABCG5 ABCB11
4	Bile secretion ³⁶	11.08	SLC10A2 SLC10A1 NR1H4 ABCG8 ABCG5 ABCC2
5	Nuclear Receptors in Lipid Metabolism and Toxicity ¹	10.9	NR1H4 ABCG5 ABCC2 ABCB4 ABCB11
6	Farnesoid X Receptor Pathway ¹	10.84	SLC10A1 NR1H4 ABCB4 ABCB11
7	Drug Induction of Bile Acid Pathway ¹	10.69	SLC10A1 NR1H4 ABCC2 ABCB11

Sources

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	plasma membrane	GO:0005886	10	TJP2 SLC10A2 SLC10A1 JAG1 GGT2 ATP8B1
2	integral component of plasma membrane	GO:0005887	9.61	SLC10A2 SLC10A1 JAG1 ATP8B1 ABCG8 ABCG5
3	apical part of cell	GO:0045177	9.54	JAG1 ABCG5 ABCB11
4	intercellular canaliculus	GO:0046581	9.33	ABCC2 ABCB4 ABCB11
5	ATP-binding cassette (ABC) transporter complex	GO:0043190	9.32	ABCG8 ABCG5
6	apical plasma membrane	GO:0016324	9.17	SLC10A2 JAG1 ATP8B1 ABCG8 ABCG5 ABCC2

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

(show all 17)

#	Name	GO ID	Score	Top Affiliating Genes
1	cholesterol homeostasis	GO:0042632	9.69	NR1H4 ABCG8 ABCG5
2	lipid transport	GO:0006869	9.62	ATP8B1 ABCG8 ABCG5 ABCB4
3	lipid homeostasis	GO:0055088	9.57	NR1H4 ABCB4
4	excretion	GO:0007588	9.56	ABCG8 ABCG5
5	phospholipid translocation	GO:0045332	9.55	ATP8B1 ABCB4
6	cholesterol efflux	GO:0033344	9.54	ABCG8 ABCG5
7	bile acid metabolic process	GO:0008206	9.52	NR1H4 ATP8B1
8	transmembrane transport	GO:0055085	9.5	SLC10A2 SLC10A1 ABCG8 ABCG5 ABCC2 ABCB4
9	leukotriene D4 biosynthetic process	GO:1901750	9.49	GGTLC3 GGT2
10	intestinal cholesterol absorption	GO:0030299	9.48	ABCG8 ABCG5
11	drug transmembrane transport	GO:0006855	9.46	ATP8B1 ABCC2
12	glutathione catabolic process	GO:0006751	9.43	GGTLC3 GGT2
13	sterol transport	GO:0015918	9.4	ABCG8 ABCG5
14	canalicular bile acid transport	GO:0015722	9.37	ABCC2 ABCB11
15	negative regulation of intestinal cholesterol absorption	GO:0045796	9.26	ABCG8 ABCG5
16	negative regulation of intestinal phytosterol absorption	GO:0010949	9.16	ABCG8 ABCG5
17	bile acid and bile salt transport	GO:0015721	9.1	SLC10A2 SLC10A1 NR1H4 ATP8B1 ABCC2 ABCB11

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	9.85	ATP8B1 ABCG8 ABCG5 ABCC2 ABCB4 ABCB11
2	ATPase activity	GO:0016887	9.35	ABCG8 ABCG5 ABCC2 ABCB4 ABCB11
3	intermembrane cholesterol transfer activity	GO:0120020	9.32	ABCG8 ABCG5
4	glutathione hydrolase activity	GO:0036374	9.26	GGTLC3 GGT2
5	bile acid:sodium symporter activity	GO:0008508	9.16	SLC10A2 SLC10A1
6	ATPase activity, coupled to transmembrane movement of substances	GO:0042626	9.02	ABCG8 ABCG5 ABCC2 ABCB4 ABCB11

Sources

Sources for Cholestasis, Progressive Familial Intrahepatic, 3

¹ BioSystems

² BitterDB

³ CDC

⁴ Cell Signaling Technology

⁵ ClinicalTrials

⁶ ClinVar

⁷ CNVD

⁸ Cochrane Library

⁹ Cosmic

¹⁰ dbSNP

¹¹ DGIdb

¹² Disease Ontology

¹³ diseasecard

¹⁴ DiseaseEnhancer

¹⁵ DISEASES

¹⁶ DrugBank

¹⁷ EFO

¹⁸ ExPASy

¹⁹ FMA

²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ Genetics Home Reference

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

²⁹ GTR

³⁰ HMDB

³¹ HPO

³² ICD10

³³ ICD10 via Orphanet

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ KEGG

³⁷ LifeMap

³⁸ LncRNADisease

³⁹ LOVD

⁴⁰ MalaCards

⁴¹ MedGen

⁴² MedlinePlus

⁴³ MeSH

⁴⁴ MESH via Orphanet

⁴⁵ MGI

⁴⁶ miR2Disease

⁴⁷ NCBI Bookshelf

⁴⁸ NCI

⁴⁹ NCIt

⁵⁰ NDF-RT

⁵¹ NIH Clinical Center

⁵² NIH Rare Diseases

⁵³ NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM

⁵⁷ OMIM via Orphanet

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubMed

⁶² PubMed Health

⁶³ QIAGEN

⁶⁴ R&D Systems

⁶⁵ Reactome

⁶⁶ Sino Biological

⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ TGDB

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ Wikipedia

Cholestasis, Progressive Familial Intrahepatic, 3 (PFIC3)

Aliases & Classifications for Cholestasis, Progressive Familial Intrahepatic, 3

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Characteristics:

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Summaries for Cholestasis, Progressive Familial Intrahepatic, 3

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

Expression 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:

GO Terms for Cholestasis, Progressive Familial Intrahepatic, 3

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

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

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

Sources for Cholestasis, Progressive Familial Intrahepatic, 3