ICP3
MCID: CHL142
MIFTS: 38

Cholestasis, Intrahepatic, of Pregnancy 3 (ICP3)

Categories: Fetal diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Rare diseases, Reproductive diseases, Skin diseases

Aliases & Classifications for Cholestasis, Intrahepatic, of Pregnancy 3

MalaCards integrated aliases for Cholestasis, Intrahepatic, of Pregnancy 3:

Name: Cholestasis, Intrahepatic, of Pregnancy 3 56 29 6 17 71
Icp3 56 12 73
Cholestasis, Intrahepatic, of Pregnancy, 3 56 13
Intrahepatic Cholestasis of Pregnancy 3 12 15
Cholestasis, Intrahepatic, of Pregnancy, Type 3 39
Cholestasis of Pregnancy, Intrahepatic 3 73
Pregnancy Related Cholestasis 3 12

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant
autosomal recessive (rare)

Miscellaneous:
occurs during pregnancy, most often in the third trimester
no chronic or permanent liver damage
oral contraceptives may also cause symptoms
see for patients with homozygous abcb4 mutations and unaffected heterozygous family members
patients with abcb4 mutations benefit from ursodeoxycholic acid (udca) treatment


HPO:

31
cholestasis, intrahepatic, of pregnancy 3:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0070229
OMIM 56 614972
MeSH 43 D002780
UMLS 71 C3554241

Summaries for Cholestasis, Intrahepatic, of Pregnancy 3

OMIM : 56 Intrahepatic cholestasis of pregnancy is a reversible form of cholestasis that occurs most often in the third trimester of pregnancy and recurs in 45 to 70% of subsequent pregnancies. Symptoms include pruritus, jaundice, increased serum bile salts, and abnormal liver enzymes, all of which resolve rapidly after delivery. However, the condition is associated with fetal complications, including placental insufficiency, premature labor, fetal distress, and intrauterine death. Women with ICP are also susceptible to oral contraceptive-induced cholestasis (OCIC). Ursodeoxycholic acid (UDCA) is an effective treatment for conditions caused by ABCB4 mutations (summary by Pasmant et al., 2012). Mutation in the ABCB4 gene accounts for about 15% of ICP cases (summary by Ziol et al., 2008). For a discussion of genetic heterogeneity of ICP, see ICP1 (147480). (614972)

MalaCards based summary : Cholestasis, Intrahepatic, of Pregnancy 3, also known as icp3, is related to gallbladder disease 1 and pericholangitis. An important gene associated with Cholestasis, Intrahepatic, of Pregnancy 3 is ABCB4 (ATP Binding Cassette Subfamily B Member 4), and among its related pathways/superpathways are Nuclear Receptors in Lipid Metabolism and Toxicity and Farnesoid X Receptor Pathway. Affiliated tissues include liver, small intestine and testes, and related phenotypes are jaundice and pruritus

Disease Ontology : 12 An intrahepatic cholestasis of pregnancy characterized by autosomal dominant inheritance that has material basis in mutation in the ABCB4 gene on chromosome 7q21.

UniProtKB/Swiss-Prot : 73 Cholestasis of pregnancy, intrahepatic 3: A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimester of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. It causes fetal distress, spontaneous premature delivery and intrauterine death. Patients have spontaneous and progressive disappearance of cholestasis after delivery. Cholestasis results from abnormal biliary transport from the liver into the small intestine.

Related Diseases for Cholestasis, Intrahepatic, of Pregnancy 3

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



Diseases related to Cholestasis, Intrahepatic, of Pregnancy 3

Symptoms & Phenotypes for Cholestasis, Intrahepatic, of Pregnancy 3

Human phenotypes related to Cholestasis, Intrahepatic, of Pregnancy 3:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 jaundice 31 occasional (7.5%) HP:0000952
2 pruritus 31 HP:0000989
3 premature birth 31 HP:0001622
4 fetal distress 31 HP:0025116
5 intrahepatic cholestasis 31 HP:0001406
6 abnormal liver function tests during pregnancy 31 HP:0200148
7 increased serum bile acid concentration during pregnancy 31 HP:0200150

Symptoms via clinical synopsis from OMIM:

56
Prenatal Manifestations Movement:
fetal distress

Abdomen Liver:
intrahepatic cholestasis during pregnancy, resolves postpartum
abnormal liver function tests during pregnancy, resolves postpartum
hepatic fibrosis seen on biopsy (in some patients)
ductal proliferation seen on biopsy (in some patients)

Skin Nails Hair Skin:
pruritus during pregnancy, resolves postpartum
jaundice (in some patients), resolves postpartum

Prenatal Manifestations Delivery:
premature delivery
intrauterine fetal death

Laboratory Abnormalities:
abnormal liver function tests during pregnancy, resolves postpartum
increased serum bile acid concentration during pregnancy, resolves postpartum

Clinical features from OMIM:

614972

Drugs & Therapeutics for Cholestasis, Intrahepatic, of Pregnancy 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Novel Non-invasive Technique of Cerebral Compliance and Auto-regulation Assessment Recruiting NCT03144219

Search NIH Clinical Center for Cholestasis, Intrahepatic, of Pregnancy 3

Genetic Tests for Cholestasis, Intrahepatic, of Pregnancy 3

Genetic tests related to Cholestasis, Intrahepatic, of Pregnancy 3:

# Genetic test Affiliating Genes
1 Cholestasis, Intrahepatic, of Pregnancy 3 29 ABCB4

Anatomical Context for Cholestasis, Intrahepatic, of Pregnancy 3

MalaCards organs/tissues related to Cholestasis, Intrahepatic, of Pregnancy 3:

40
Liver, Small Intestine, Testes

Publications for Cholestasis, Intrahepatic, of Pregnancy 3

Articles related to Cholestasis, Intrahepatic, of Pregnancy 3:

(show all 17)
# Title Authors PMID Year
1
ABCB4 gene mutations and single-nucleotide polymorphisms in women with intrahepatic cholestasis of pregnancy. 56 6
19584064 2009
2
ABCB4 heterozygous gene mutations associated with fibrosing cholestatic liver disease in adults. 56 6
18482588 2008
3
MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis. 56 6
11313316 2001
4
Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking. 56 6
10767346 2000
5
Heterozygous non-sense mutation of the MDR3 gene in familial intrahepatic cholestasis of pregnancy. 6 56
9923886 1999
6
First description of ABCB4 gene deletions in familial low phospholipid-associated cholelithiasis and oral contraceptives-induced cholestasis. 56
21989363 2012
7
Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. 56
9419367 1998
8
Defect of multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis. 6
8666348 1996
9
Niche adaptation limits bacteriophage predation of Vibrio cholerae in a nutrient-poor aquatic environment. 61
30635420 2019
10
Vibrio cholerae Outer Membrane Vesicles Inhibit Bacteriophage Infection. 61
29661863 2018
11
Mechanisms of the evolutionary arms race between Vibrio cholerae and Vibriophage clinical isolates. 61
29446802 2017
12
Evidence of a dominant lineage of Vibrio cholerae-specific lytic bacteriophages shed by cholera patients over a 10-year period in Dhaka, Bangladesh. 61
21304168 2011
13
Detection by HPLC-ICP of metallothionein in serum of an epileptic child with valproate-associated hepatotoxicity. 61
1304235 1992
14
Calcium transport pathways of pancreatic acinar cells. 61
2540704 1989
15
Inositol 1,2-cyclic 4,5-trisphosphate concentration relative to inositol 1,4,5-trisphosphate in pancreatic minilobules on stimulation with carbamylcholine in the absence of lithium. Possible role as a second messenger in long- but not short-term responses. 61
3498721 1987
16
The formation of inositol 1,2-cyclic 4,5-trisphosphate and inositol 1,2-cyclic 4-bisphosphate on stimulation of mouse pancreatic minilobules with carbamylcholine. 61
3491823 1987
17
Biochemical aspects of the phosphoinositide signalling system with special reference to the formation of inositol cyclic phosphates and arachidonic acid and metabolites on agonist stimulation. 61
2823545 1987

Variations for Cholestasis, Intrahepatic, of Pregnancy 3

ClinVar genetic disease variations for Cholestasis, Intrahepatic, of Pregnancy 3:

6 (show top 50) (show all 103) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ABCB4 NM_000443.4(ABCB4):c.3486+1G>ASNV Pathogenic 501724 rs764513998 7:87035603-87035603 7:87406287-87406287
2 ABCB4 NM_000443.4(ABCB4):c.3136C>T (p.Arg1046Ter)SNV Pathogenic 587488 rs759202962 7:87037496-87037496 7:87408180-87408180
3 ABCB4 NM_000443.4(ABCB4):c.475C>T (p.Arg159Ter)SNV Pathogenic 596680 rs377160065 7:87082321-87082321 7:87453005-87453005
4 ABCB4 NM_000443.4(ABCB4):c.2044del (p.Asp682fs)deletion Pathogenic 617459 rs1562965036 7:87056086-87056086 7:87426770-87426770
5 ABCB11 NM_003742.4(ABCB11):c.3669G>C (p.Glu1223Asp)SNV Pathogenic 812747 2:169781263-169781263 2:168924753-168924753
6 ABCB4 NM_000443.4(ABCB4):c.2683-883_2783+345deldeletion Pathogenic 812921 7:87042588-87043916 7:87413272-87414600
7 ABCB4 NM_000443.4(ABCB4):c.1015dup (p.Ser339fs)duplication Pathogenic 812984 7:87074281-87074282 7:87444965-87444966
8 ABCB11 NM_003742.4(ABCB11):c.890A>G (p.Glu297Gly)SNV Pathogenic 6590 rs11568372 2:169847329-169847329 2:168990819-168990819
9 ABCB4 NM_000443.4(ABCB4):c.1712del (p.Val571fs)deletion Pathogenic 13688 rs387906527 7:87069002-87069002 7:87439686-87439686
10 ABCB4 NM_000443.4(ABCB4):c.1328_1329delinsCAA (p.Gln443fs)indel Pathogenic 13693 rs387906528 7:87072662-87072663 7:87443346-87443347
11 ABCB4 NM_000443.4(ABCB4):c.430C>T (p.Arg144Ter)SNV Pathogenic 13696 rs72552780 7:87082366-87082366 7:87453050-87453050
12 ABCB11 NM_003742.4(ABCB11):c.2012-8T>GSNV Pathogenic/Likely pathogenic 284637 rs769910565 2:169825008-169825008 2:168968498-168968498
13 ABCB4 NM_000443.4(ABCB4):c.2869C>T (p.Arg957Ter)SNV Likely pathogenic 13687 rs121918440 7:87041264-87041264 7:87411948-87411948
14 ABCB4 NM_000443.4(ABCB4):c.905G>A (p.Gly302Asp)SNV Likely pathogenic 812750 7:87076450-87076450 7:87447134-87447134
15 ABCB4 NM_000443.4(ABCB4):c.893del (p.Asn298fs)deletion Likely pathogenic 812751 7:87076462-87076462 7:87447146-87447146
16 ABCB4 NM_000443.4(ABCB4):c.652del (p.Leu218_Val219insTer)deletion Likely pathogenic 812753 7:87080995-87080995 7:87451679-87451679
17 ABCB4 NM_000443.4(ABCB4):c.449G>A (p.Arg150Lys)SNV Likely pathogenic 812754 7:87082347-87082347 7:87453031-87453031
18 ABCB11 NM_003742.4(ABCB11):c.2075+2T>CSNV Likely pathogenic 812748 2:169824935-169824935 2:168968425-168968425
19 ABCB4 NM_000443.4(ABCB4):c.1357-2A>CSNV Likely pathogenic 812982 7:87069720-87069720 7:87440404-87440404
20 ABCB4 NM_000443.4(ABCB4):c.1119+1G>TSNV Likely pathogenic 812983 7:87074177-87074177 7:87444861-87444861
21 ABCB4 NM_000443.4(ABCB4):c.834-1G>ASNV Likely pathogenic 812752 7:87076522-87076522 7:87447206-87447206
22 ABCB4 NM_000443.4(ABCB4):c.2556C>A (p.Tyr852Ter)SNV Likely pathogenic 812979 7:87046754-87046754 7:87417438-87417438
23 ABCB4 NM_000443.4(ABCB4):c.1801G>T (p.Ala601Ser)SNV Likely pathogenic 812980 7:87060812-87060812 7:87431496-87431496
24 ABCB4 NM_000443.4(ABCB4):c.1778C>T (p.Thr593Met)SNV Likely pathogenic 812981 7:87060835-87060835 7:87431519-87431519
25 ABCB11 NM_003742.4(ABCB11):c.1623C>G (p.Ile541Met)SNV Likely pathogenic 812749 2:169828372-169828372 2:168971862-168971862
26 ABCB4 NM_000443.4(ABCB4):c.3535C>T (p.Gln1179Ter)SNV Likely pathogenic 812975 7:87032549-87032549 7:87403233-87403233
27 ABCB4 NM_000443.4(ABCB4):c.3434dup (p.Ser1146fs)duplication Likely pathogenic 812976 7:87035655-87035656 7:87406339-87406340
28 ABCB4 NM_000443.4(ABCB4):c.3224A>T (p.Lys1075Met)SNV Likely pathogenic 812977 7:87037408-87037408 7:87408092-87408092
29 ABCB4 NM_000443.4(ABCB4):c.2880_2881AT[1] (p.Tyr961fs)short repeat Likely pathogenic 812978 7:87041250-87041251 7:87411934-87411935
30 ABCB11 NM_003742.4(ABCB11):c.3677G>T (p.Arg1226Leu)SNV Likely pathogenic 812746 2:169781255-169781255 2:168924745-168924745
31 ABCB4 NM_000443.4(ABCB4):c.1952C>A (p.Thr651Asn)SNV Conflicting interpretations of pathogenicity 594313 rs45476795 7:87056178-87056178 7:87426862-87426862
32 ABCB4 NM_000443.4(ABCB4):c.1769G>A (p.Arg590Gln)SNV Conflicting interpretations of pathogenicity 13697 rs45575636 7:87060844-87060844 7:87431528-87431528
33 ABCB4 NM_000443.4(ABCB4):c.959C>T (p.Ser320Phe)SNV Conflicting interpretations of pathogenicity 13690 rs72552778 7:87076396-87076396 7:87447080-87447080
34 ABCB4 NM_000443.4(ABCB4):c.3402C>T (p.Asp1134=)SNV Conflicting interpretations of pathogenicity 598178 rs371394487 7:87035688-87035688 7:87406372-87406372
35 ABCB4 NM_000443.4(ABCB4):c.101C>T (p.Thr34Met)SNV Conflicting interpretations of pathogenicity 196273 rs142794414 7:87101971-87101971 7:87472655-87472655
36 ABCB4 NM_000443.4(ABCB4):c.1893+6T>CSNV Conflicting interpretations of pathogenicity 256159 rs8187798 7:87060714-87060714 7:87431398-87431398
37 ABCB4 NM_000443.4(ABCB4):c.2800G>A (p.Ala934Thr)SNV Conflicting interpretations of pathogenicity 281139 rs61730509 7:87041333-87041333 7:87412017-87412017
38 ABCB4 NM_000443.4(ABCB4):c.3037A>C (p.Arg1013=)SNV Conflicting interpretations of pathogenicity 282951 rs2230029 7:87038596-87038596 7:87409280-87409280
39 ABCB11 NM_003742.4(ABCB11):c.1460G>A (p.Arg487His)SNV Conflicting interpretations of pathogenicity 290081 rs188824058 2:169828535-169828535 2:168972025-168972025
40 ABCB4 NM_000443.4(ABCB4):c.1529A>G (p.Asn510Ser)SNV Conflicting interpretations of pathogenicity 291252 rs375315619 7:87069546-87069546 7:87440230-87440230
41 ABCB4 NM_000443.4(ABCB4):c.3372C>T (p.Cys1124=)SNV Conflicting interpretations of pathogenicity 360790 rs886062459 7:87035718-87035718 7:87406402-87406402
42 ABCB4 NM_000443.4(ABCB4):c.3285C>T (p.Leu1095=)SNV Conflicting interpretations of pathogenicity 360791 rs561612231 7:87035805-87035805 7:87406489-87406489
43 ABCB4 NM_000443.4(ABCB4):c.3543G>A (p.Gln1181=)SNV Conflicting interpretations of pathogenicity 383483 rs140592811 7:87032541-87032541 7:87403225-87403225
44 ABCB4 NM_000443.4(ABCB4):c.2144C>T (p.Thr715Ile)SNV Conflicting interpretations of pathogenicity 381720 rs138773456 7:87053289-87053289 7:87423973-87423973
45 ABCB4 NM_000443.4(ABCB4):c.2055C>T (p.Thr685=)SNV Uncertain significance 360795 rs747255117 7:87056075-87056075 7:87426759-87426759
46 ABCB4 NM_000443.4(ABCB4):c.2047G>A (p.Val683Met)SNV Uncertain significance 360796 rs776616540 7:87056083-87056083 7:87426767-87426767
47 ABCB4 NM_000443.4(ABCB4):c.2535T>C (p.Gly845=)SNV Uncertain significance 360793 rs545534537 7:87046775-87046775 7:87417459-87417459
48 ABCB4 NM_000443.4(ABCB4):c.1858A>G (p.Lys620Glu)SNV Uncertain significance 360800 rs886062460 7:87060755-87060755 7:87431439-87431439
49 ABCB4 NM_000443.4(ABCB4):c.-18G>TSNV Uncertain significance 360805 rs886062461 7:87104961-87104961 7:87475645-87475645
50 ABCB4 NM_000443.4(ABCB4):c.217C>G (p.Leu73Val)SNV Uncertain significance 374521 rs8187788 7:87092143-87092143 7:87462827-87462827

UniProtKB/Swiss-Prot genetic disease variations for Cholestasis, Intrahepatic, of Pregnancy 3:

73
# Symbol AA change Variation ID SNP ID
1 ABCB4 p.Ala546Asp VAR_023503 rs121918441
2 ABCB4 p.Arg150Lys VAR_043081 rs757693457
3 ABCB4 p.Gly762Glu VAR_043099

Expression for Cholestasis, Intrahepatic, of Pregnancy 3

Search GEO for disease gene expression data for Cholestasis, Intrahepatic, of Pregnancy 3.

Pathways for Cholestasis, Intrahepatic, of Pregnancy 3

Pathways related to Cholestasis, Intrahepatic, of Pregnancy 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.5 ABCB4 ABCB11
2 9.9 ABCB4 ABCB11

GO Terms for Cholestasis, Intrahepatic, of Pregnancy 3

Cellular components related to Cholestasis, Intrahepatic, of Pregnancy 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 intercellular canaliculus GO:0046581 8.62 ABCB4 ABCB11

Molecular functions related to Cholestasis, Intrahepatic, of Pregnancy 3 according to GeneCards Suite gene sharing:

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

Sources for Cholestasis, Intrahepatic, of Pregnancy 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
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39 LOVD
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43 MeSH
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50 NDF-RT
53 NINDS
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56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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