FHCA1
MCID: HYP872
MIFTS: 32

Hypercholanemia, Familial 1 (FHCA1)

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

Aliases & Classifications for Hypercholanemia, Familial 1

MalaCards integrated aliases for Hypercholanemia, Familial 1:

Name: Hypercholanemia, Familial 1 57
Hypercholanemia, Familial 57 29 13 6 39 70
Familial Hypercholanemia 58 72 36
Hereditary Hypercholanemia 58
Bile Acid, Elevated Serum 57
Fhca1 57
Fhca 72

Characteristics:

Orphanet epidemiological data:

58
familial hypercholanemia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
incomplete penetrance
onset in infancy
variable severity
liver damage may improve with age
reported in old order amish population

Inheritance:
autosomal recessive


HPO:

31
hypercholanemia, familial 1:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare hepatic diseases
Inborn errors of metabolism


External Ids:

OMIM® 57 607748
OMIM Phenotypic Series 57 PS607748
KEGG 36 H01935
MeSH 44 D008286
UMLS via Orphanet 71 C1843139
Orphanet 58 ORPHA238475
MedGen 41 C1843139
UMLS 70 C1843139

Summaries for Hypercholanemia, Familial 1

OMIM® : 57 Familial hypercholanemia-1 (FHCA1) is an autosomal recessive disorder characterized by elevated concentrations of bile acids (usually conjugated), itching, and fat malabsorption, leading to poor overall growth and deficiencies of fat-soluble vitamins. Vitamin D deficiency results in rickets, and vitamin K deficiency results in a coagulopathy (Morton et al., 2000; Shneider et al., 1997; summary by Carlton et al., 2003). See also bile acid conjugation defect-1 (BACD1; 619232), which can also show increased bile acid levels, although the bile acids in BACD1 are unconjugated. (607748) (Updated 20-May-2021)

MalaCards based summary : Hypercholanemia, Familial 1, also known as hypercholanemia, familial, is related to bile acid conjugation defect 1 and hypercholanemia, familial, 2. An important gene associated with Hypercholanemia, Familial 1 is TJP2 (Tight Junction Protein 2), and among its related pathways/superpathways is Bile secretion. Affiliated tissues include liver and bone, and related phenotypes are failure to thrive and rickets

KEGG : 36 Familial hypercholanemia is characterized by elevated serum bile acid concentrations, itching, and fat malabsorption. Mutations in EPHX1, TJP2, and BAAT may disrupt bile acid transport and circulation.

UniProtKB/Swiss-Prot : 72 Familial hypercholanemia: A disorder characterized by elevated serum bile acid concentrations, itching, and fat malabsorption.

Related Diseases for Hypercholanemia, Familial 1

Diseases in the Hypercholanemia, Familial 1 family:

Hypercholanemia, Familial, 2

Diseases related to Hypercholanemia, Familial 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 bile acid conjugation defect 1 11.1
2 hypercholanemia, familial, 2 10.9
3 cystic fibrosis 10.0
4 atp8b1 deficiency 10.0
5 cholestasis, progressive familial intrahepatic, 4 9.4 TJP2 BAAT

Graphical network of the top 20 diseases related to Hypercholanemia, Familial 1:



Diseases related to Hypercholanemia, Familial 1

Symptoms & Phenotypes for Hypercholanemia, Familial 1

Human phenotypes related to Hypercholanemia, Familial 1:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 31 HP:0001508
2 rickets 31 HP:0002748
3 steatorrhea 31 HP:0002570
4 pruritus 31 HP:0000989
5 low levels of vitamin k 31 HP:0011892
6 increased serum bile acid concentration 31 HP:0012202

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive
poor growth

Hematology:
anemia
coagulopathy due to deficiency of vitamin k-dependent clotting factors
increased pt and ptt

Abdomen Liver:
hepatomegaly (in some patients)
increased serum levels of bile acids
increased bilirubin (variable)
increased liver enzymes (variable)
intrahepatic cholestasis on liver biopsy

Laboratory Abnormalities:
elevated serum conjugated bile acids (hypercholanemia)

Skeletal:
rickets
bone fractures

Skin Nails Hair Skin:
jaundice
petechiae
ecchymoses

Abdomen Gastrointestinal:
impaired fat absorption
impaired absorption of fat-soluble vitamins (d and k)

Clinical features from OMIM®:

607748 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Hypercholanemia, Familial 1 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased Hepatitis C virus replication GR00180-A-1 8.8 BAAT TJP2
2 Decreased Hepatitis C virus replication GR00180-A-2 8.8 BAAT

Drugs & Therapeutics for Hypercholanemia, Familial 1

Search Clinical Trials , NIH Clinical Center for Hypercholanemia, Familial 1

Genetic Tests for Hypercholanemia, Familial 1

Genetic tests related to Hypercholanemia, Familial 1:

# Genetic test Affiliating Genes
1 Hypercholanemia, Familial 29 BAAT EPHX1 TJP2

Anatomical Context for Hypercholanemia, Familial 1

MalaCards organs/tissues related to Hypercholanemia, Familial 1:

40
Liver, Bone

Publications for Hypercholanemia, Familial 1

Articles related to Hypercholanemia, Familial 1:

# Title Authors PMID Year
1
Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. 61 57 6
12704386 2003
2
Abnormal hepatic sinusoidal bile acid transport in an Amish kindred is not linked to FIC1 and is improved by ursodiol. 57
10889168 2000
3
Hepatic basolateral sodium-dependent-bile acid transporter expression in two unusual cases of hypercholanemia and in extrahepatic biliary atresia. 57
9141436 1997
4
Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. 61
15521008 2004

Variations for Hypercholanemia, Familial 1

ClinVar genetic disease variations for Hypercholanemia, Familial 1:

6 (show top 50) (show all 90)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TJP2 NM_004817.4(TJP2):c.143T>C (p.Val48Ala) SNV Pathogenic 2907 rs121918299 GRCh37: 9:71831283-71831283
GRCh38: 9:69216367-69216367
2 TJP2 NM_004817.4(TJP2):c.1056+2T>C SNV Likely pathogenic 489223 rs1278244243 GRCh37: 9:71840325-71840325
GRCh38: 9:69225409-69225409
3 TJP2 NM_004817.4(TJP2):c.3371C>T (p.Thr1124Met) SNV Likely pathogenic 367235 rs376663560 GRCh37: 9:71867780-71867780
GRCh38: 9:69252864-69252864
4 TJP2 NM_004817.4(TJP2):c.185C>T (p.Thr62Met) SNV Likely pathogenic 165403 rs138241615 GRCh37: 9:71831325-71831325
GRCh38: 9:69216409-69216409
5 TJP2 NM_004817.4(TJP2):c.659G>T (p.Ser220Ile) SNV Uncertain significance 1030845 GRCh37: 9:71836119-71836119
GRCh38: 9:69221203-69221203
6 BAAT NM_001701.4(BAAT):c.1039C>T (p.His347Tyr) SNV Uncertain significance 913864 GRCh37: 9:104124928-104124928
GRCh38: 9:101362646-101362646
7 EPHX1 NM_000120.4(EPHX1):c.823A>G (p.Thr275Ala) SNV Uncertain significance 561152 rs35073925 GRCh37: 1:226027630-226027630
GRCh38: 1:225839929-225839929
8 BAAT NM_001701.4(BAAT):c.*95C>T SNV Uncertain significance 913862 GRCh37: 9:104124615-104124615
GRCh38: 9:101362333-101362333
9 BAAT NM_001701.4(BAAT):c.*1041A>G SNV Uncertain significance 915070 GRCh37: 9:104123669-104123669
GRCh38: 9:101361387-101361387
10 BAAT NM_001701.4(BAAT):c.*936T>C SNV Uncertain significance 915071 GRCh37: 9:104123774-104123774
GRCh38: 9:101361492-101361492
11 BAAT NM_001701.4(BAAT):c.561C>T (p.Ala187=) SNV Uncertain significance 915107 GRCh37: 9:104130510-104130510
GRCh38: 9:101368228-101368228
12 BAAT NM_001701.4(BAAT):c.558C>T (p.Phe186=) SNV Uncertain significance 915108 GRCh37: 9:104130513-104130513
GRCh38: 9:101368231-101368231
13 TJP2 NM_004817.4(TJP2):c.1258C>T (p.Arg420Cys) SNV Uncertain significance 178543 rs199761505 GRCh37: 9:71842728-71842728
GRCh38: 9:69227812-69227812
14 BAAT NM_001701.4(BAAT):c.1186G>T (p.Glu396Ter) SNV Uncertain significance 632531 rs371796700 GRCh37: 9:104124781-104124781
GRCh38: 9:101362499-101362499
15 BAAT NM_001701.4(BAAT):c.*1864G>T SNV Uncertain significance 912310 GRCh37: 9:104122846-104122846
GRCh38: 9:101360564-101360564
16 BAAT NM_001701.4(BAAT):c.*1828C>T SNV Uncertain significance 912311 GRCh37: 9:104122882-104122882
GRCh38: 9:101360600-101360600
17 BAAT NM_001701.4(BAAT):c.*1712G>C SNV Uncertain significance 912312 GRCh37: 9:104122998-104122998
GRCh38: 9:101360716-101360716
18 BAAT NM_001701.4(BAAT):c.*831A>G SNV Uncertain significance 912350 GRCh37: 9:104123879-104123879
GRCh38: 9:101361597-101361597
19 BAAT NM_001701.4(BAAT):c.*668A>G SNV Uncertain significance 912351 GRCh37: 9:104124042-104124042
GRCh38: 9:101361760-101361760
20 BAAT NM_001701.4(BAAT):c.*660G>T SNV Uncertain significance 912352 GRCh37: 9:104124050-104124050
GRCh38: 9:101361768-101361768
21 BAAT NM_001701.4(BAAT):c.-183T>A SNV Uncertain significance 364285 rs886063285 GRCh37: 9:104147260-104147260
GRCh38: 9:101384978-101384978
22 BAAT NM_001701.4(BAAT):c.*573G>T SNV Uncertain significance 912354 GRCh37: 9:104124137-104124137
GRCh38: 9:101361855-101361855
23 BAAT NM_001701.4(BAAT):c.390G>T (p.Arg130Ser) SNV Uncertain significance 912408 GRCh37: 9:104133297-104133297
GRCh38: 9:101371015-101371015
24 BAAT NM_001701.4(BAAT):c.147C>T (p.His49=) SNV Uncertain significance 912409 GRCh37: 9:104133540-104133540
GRCh38: 9:101371258-101371258
25 BAAT NM_001701.4(BAAT):c.126C>A (p.Asp42Glu) SNV Uncertain significance 912410 GRCh37: 9:104133561-104133561
GRCh38: 9:101371279-101371279
26 BAAT NM_001701.4(BAAT):c.*1597C>A SNV Uncertain significance 913431 GRCh37: 9:104123113-104123113
GRCh38: 9:101360831-101360831
27 BAAT NM_001701.4(BAAT):c.*1557C>A SNV Uncertain significance 913432 GRCh37: 9:104123153-104123153
GRCh38: 9:101360871-101360871
28 BAAT NM_001701.4(BAAT):c.*1528C>A SNV Uncertain significance 913433 GRCh37: 9:104123182-104123182
GRCh38: 9:101360900-101360900
29 BAAT NM_001701.4(BAAT):c.*1422A>G SNV Uncertain significance 913434 GRCh37: 9:104123288-104123288
GRCh38: 9:101361006-101361006
30 BAAT NM_001701.4(BAAT):c.*538T>C SNV Uncertain significance 913483 GRCh37: 9:104124172-104124172
GRCh38: 9:101361890-101361890
31 BAAT NM_001701.4(BAAT):c.*426A>G SNV Uncertain significance 913484 GRCh37: 9:104124284-104124284
GRCh38: 9:101362002-101362002
32 BAAT NM_001701.4(BAAT):c.*365T>C SNV Uncertain significance 913485 GRCh37: 9:104124345-104124345
GRCh38: 9:101362063-101362063
33 BAAT NM_001701.4(BAAT):c.*224A>T SNV Uncertain significance 913487 GRCh37: 9:104124486-104124486
GRCh38: 9:101362204-101362204
34 BAAT NM_001701.4(BAAT):c.22C>G (p.Pro8Ala) SNV Uncertain significance 913526 GRCh37: 9:104133665-104133665
GRCh38: 9:101371383-101371383
35 BAAT NM_001701.4(BAAT):c.17C>T (p.Ala6Val) SNV Uncertain significance 913527 GRCh37: 9:104133670-104133670
GRCh38: 9:101371388-101371388
36 BAAT NM_001701.4(BAAT):c.-92C>T SNV Uncertain significance 913528 GRCh37: 9:104147169-104147169
GRCh38: 9:101384887-101384887
37 BAAT NM_001701.4(BAAT):c.-176C>T SNV Uncertain significance 913529 GRCh37: 9:104147253-104147253
GRCh38: 9:101384971-101384971
38 BAAT NM_001701.4(BAAT):c.*1341A>G SNV Uncertain significance 913811 GRCh37: 9:104123369-104123369
GRCh38: 9:101361087-101361087
39 BAAT NM_001701.4(BAAT):c.*1307T>A SNV Uncertain significance 913812 GRCh37: 9:104123403-104123403
GRCh38: 9:101361121-101361121
40 BAAT NM_001701.4(BAAT):c.*1130A>G SNV Uncertain significance 913813 GRCh37: 9:104123580-104123580
GRCh38: 9:101361298-101361298
41 EPHX1 EPHX1, -4238T-A SNV Uncertain significance 16606 GRCh37:
GRCh38:
42 EPHX1 EPHX1, 2557C-G SNV Uncertain significance 16607 GRCh37:
GRCh38:
43 BAAT NM_001701.4(BAAT):c.*1139T>G SNV Uncertain significance 364260 rs188189145 GRCh37: 9:104123571-104123571
GRCh38: 9:101361289-101361289
44 BAAT NM_001701.4(BAAT):c.473G>T (p.Gly158Val) SNV Uncertain significance 364279 rs746409843 GRCh37: 9:104130598-104130598
GRCh38: 9:101368316-101368316
45 BAAT NM_001701.4(BAAT):c.780C>T (p.Thr260=) SNV Uncertain significance 364278 rs886063283 GRCh37: 9:104125187-104125187
GRCh38: 9:101362905-101362905
46 BAAT NM_001701.4(BAAT):c.-208C>T SNV Uncertain significance 364286 rs886063286 GRCh37: 9:104147285-104147285
GRCh38: 9:101385003-101385003
47 BAAT NM_001701.4(BAAT):c.264A>G (p.Leu88=) SNV Uncertain significance 364281 rs886063284 GRCh37: 9:104133423-104133423
GRCh38: 9:101371141-101371141
48 BAAT NM_001701.4(BAAT):c.-59-14C>A SNV Uncertain significance 364283 rs777417694 GRCh37: 9:104133759-104133759
GRCh38: 9:101371477-101371477
49 BAAT NM_001701.4(BAAT):c.*1575T>G SNV Uncertain significance 364252 rs886063281 GRCh37: 9:104123135-104123135
GRCh38: 9:101360853-101360853
50 BAAT NM_001701.4(BAAT):c.*1136A>G SNV Uncertain significance 364261 rs886063282 GRCh37: 9:104123574-104123574
GRCh38: 9:101361292-101361292

UniProtKB/Swiss-Prot genetic disease variations for Hypercholanemia, Familial 1:

72
# Symbol AA change Variation ID SNP ID
1 BAAT p.Met76Val VAR_023737 rs28937579
2 TJP2 p.Val48Ala VAR_016004 rs121918299

Expression for Hypercholanemia, Familial 1

Search GEO for disease gene expression data for Hypercholanemia, Familial 1.

Pathways for Hypercholanemia, Familial 1

Pathways related to Hypercholanemia, Familial 1 according to KEGG:

36
# Name Kegg Source Accession
1 Bile secretion hsa04976

Pathways related to Hypercholanemia, Familial 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.58 EPHX1 BAAT

GO Terms for Hypercholanemia, Familial 1

Sources for Hypercholanemia, Familial 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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