Details of Disease

General Information of Disease (ID: DIS3J8HT)

Disease Name	Progressive familial intrahepatic cholestasis
Synonyms	PFIC; cholestasis, progressive familial intrahepatic
Disease Class	5C58: Inborn porphyrin/heme metabolism error
Definition	Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin.
Disease Hierarchy	DIS6SVEE: Syndromic disease DIS5RL11: Familial intrahepatic cholestasis DISFGCQF: Inborn disorder of bilirubin metabolism DIS3J8HT: Progressive familial intrahepatic cholestasis
ICD Code	ICD-11 ICD-11: 5C58.03 ICD-10 ICD-10: K76.8 Expand ICD-11 '5C58.03 Expand ICD-10 'K76.8
Disease Identifiers	MONDO ID MONDO_0015762 UMLS CUI C0268312 MedGen ID 75668 Orphanet ID 172 SNOMED CT ID 74162007

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Maralixibat	DMJCF1O	Approved	Small molecular drug	[1]
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This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
LUM001	DMQZXDW	Phase 2	NA	[2]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ABCC4	TTUEAFL	Limited	Genetic Variation	[3]
ABCB11	TTUXCAF	Strong	Genetic Variation	[4]
ABCB4	TTJUXV6	Strong	Biomarker	[5]
GGT1	TTZVT7O	Strong	Genetic Variation	[6]
NR1H4	TTS4UGC	Strong	Biomarker	[7]
SLC10A2	TTPI1M5	Strong	Altered Expression	[8]
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⏷ Show the Full List of 6 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A13	DTDSYAQ	Strong	Genetic Variation	[9]
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This Disease Is Related to 9 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
HSD3B7	OT2Y9IW4	Limited	Genetic Variation	[10]
KLHL1	OTAX6SAD	Limited	Biomarker	[11]
MYO5B	OTCKL3W3	Limited	Genetic Variation	[12]
SYCE1L	OTXU44F3	Limited	Biomarker	[11]
TJP2	OTQUY6BV	Limited	Genetic Variation	[13]
ATP8B1	OTALGS63	Strong	Biomarker	[14]
GGTLC1	OTWJKUHQ	Strong	Altered Expression	[15]
IBSP	OT29944Y	Strong	Genetic Variation	[16]
IMMT	OTBDSLE7	Strong	Genetic Variation	[12]
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⏷ Show the Full List of 9 DOT(s)

References

1	ClinicalTrials.gov (NCT04185363) An Extension Study of Maralixibat in Patients With Progressive Familial Intrahepatic Cholestasis (PFIC). U.S. National Institutes of Health.
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	MDR3 (ABCB4) defects: a paradigm for the genetics of adult cholestatic syndromes.Semin Liver Dis. 2007 Feb;27(1):77-98. doi: 10.1055/s-2006-960172.
4	Drugs and hepatic transporters: A review.Pharmacol Res. 2020 Apr;154:104234. doi: 10.1016/j.phrs.2019.04.018. Epub 2019 Apr 17.
5	ABCB4 disease: Many faces of one gene deficiency.Ann Hepatol. 2020 Mar-Apr;19(2):126-133. doi: 10.1016/j.aohep.2019.09.010. Epub 2019 Oct 31.
6	Long-term outcomes after cholecystocolostomy for progressive familial intrahepatic cholestasis.Hepatol Res. 2018 Dec;48(13):1163-1171. doi: 10.1111/hepr.13222. Epub 2018 Jul 27.
7	Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases.J Biomed Sci. 2018 Oct 26;25(1):75. doi: 10.1186/s12929-018-0475-8.
8	Progressive familial intrahepatic cholestasis, type 1, is associated with decreased farnesoid X receptor activity.Gastroenterology. 2004 Mar;126(3):756-64. doi: 10.1053/j.gastro.2003.12.013.
9	Utility of oligonucleotide array-based comparative genomic hybridization for detection of target gene deletions.Clin Chem. 2008 Jul;54(7):1141-8. doi: 10.1373/clinchem.2008.103721. Epub 2008 May 16.
10	Cryptogenic cholestasis in young and adults: ATP8B1, ABCB11, ABCB4, and TJP2 gene variants analysis by high-throughput sequencing.J Gastroenterol. 2018 Aug;53(8):945-958. doi: 10.1007/s00535-017-1423-1. Epub 2017 Dec 13.
11	Bile acid transport correlative protein mRNA expression profile in human placenta with intrahepatic cholestasis of pregnancy.Saudi Med J. 2009 Nov;30(11):1406-10.
12	A Molecular Mechanism Underlying Genotype-Specific Intrahepatic Cholestasis Resulting From MYO5B Mutations.Hepatology. 2020 Jul;72(1):213-229. doi: 10.1002/hep.31002. Epub 2020 Apr 23.
13	Novel compound heterozygote mutations of TJP2 in a Chinese child with progressive cholestatic liver disease.BMC Med Genet. 2019 Jan 18;20(1):18. doi: 10.1186/s12881-019-0753-7.
14	Dual catenin loss in murine liver causes tight junctional deregulation and progressive intrahepatic cholestasis.Hepatology. 2018 Jun;67(6):2320-2337. doi: 10.1002/hep.29585. Epub 2018 Apr 19.
15	Comorbidity between progressive familial intrahepatic cholestasis and atopic dermatitis in a 19-month-old child.BMJ Case Rep. 2019 Oct 18;12(10):e230152. doi: 10.1136/bcr-2019-230152.
16	A study of inheritance in progressive intrahepatic cholestasis: hepatic excretory function in unaffected family members.Pediatr Res. 1979 Sep;13(9):1002-5. doi: 10.1203/00006450-197909000-00010.