CBAS2
MCID: BLC008
MIFTS: 49

Bile Acid Synthesis Defect, Congenital, 2 (CBAS2)

Categories: Blood diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Oral diseases, Rare diseases

Aliases & Classifications for Bile Acid Synthesis Defect, Congenital, 2

MalaCards integrated aliases for Bile Acid Synthesis Defect, Congenital, 2:

Name: Bile Acid Synthesis Defect, Congenital, 2 57 13 44 70
Cholestasis with Delta(4)-3-Oxosteroid 5-Beta-Reductase Deficiency 57 12 20 43 58 72
Congenital Bile Acid Synthesis Defect 2 12 72 29 6 15
Cbas2 57 12 20 43 72
Congenital Bile Acid Synthesis Defect Type 2 43 58
Bile Acid Synthesis Defect, Congenital, Type 2 39
Congenital Bile Acid Synthesis Defect, Type 2 20
Basd2 58

Characteristics:

Orphanet epidemiological data:

58
congenital bile acid synthesis defect type 2
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: infantile;

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
neonatal onset
favorable response to oral bile acid therapy
caused by inborn error in bile acid synthesis

Inheritance:
autosomal recessive


HPO:

31
bile acid synthesis defect, congenital, 2:
Inheritance autosomal recessive inheritance
Onset and clinical course neonatal onset


Classifications:

Orphanet: 58  
Rare hepatic diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0111069
OMIM® 57 235555
OMIM Phenotypic Series 57 PS607765
MESH via Orphanet 45 C535443
ICD10 via Orphanet 33 K76.8
UMLS via Orphanet 71 C1856127
Orphanet 58 ORPHA79303
MedGen 41 C1856127
UMLS 70 C1856127

Summaries for Bile Acid Synthesis Defect, Congenital, 2

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 79303 Definition Congenital bile acid synthesis defect type 2 (BAS defect type 2) is an anomaly of bile acid synthesis (see this term) characterized by severe and rapidly progressive cholestatic liver disease, and malabsorption of fat and fat-soluble vitamins. Epidemiology Prevalence is unknown. This condition is clearly rare but is the second most common anomaly of BAS on screening infants with cholestasis. Clinical description Patients present with neonatal cholestasis and rapid progression to cirrhosis and death in infancy without intervention. The clinical presentation resembles that of congenital BAS defect type 1 (see this term) with hepatosplenomegaly, jaundice, fat-soluble vitamin malabsorption, and steatorrhea. However, the average age at diagnosis is lower, in infancy, and disease progression is more rapid and severe. Liver function tests present elevated serum transaminases (AST, ALT) and gamma-GT, markedly elevated conjugated bilirubinemia and coagulopathy. Etiology BAS defect type 2 is caused by a mutation in the delta(4)-3-oxosteroid 5-beta-reductase gene ( AKR1D1, 7q32-q33). Transmission is autosomal recessive. Liver injury is thought to be caused by diminished primary bile acid synthesis and hepatotoxicity of accumulated atypical bile acids (delta(4)-3-oxo bile acids). Diagnostic methods Diagnosis is based on urine analysis using liquid secondary ionization mass spectrometry (LSIMS) and gas chromatography - mass spectrometry (GC-MS). LSIMS urine analysis reveals elevated amounts of delta(4)-3-oxo bile acids including 3-oxo-7alpha-hydroxy-4-cholenoic and 3-oxo-7alpha, 12alpha-dihydroxy-4-cholenoic acids. Increased production of delta4-3-oxo bile acids occurs in infants during the first few weeks of life and in patients with end-stage liver disease of other causes. It is important to perform repeat LSIMS urine analysis as, on rare occasions, a resolution of the liver disease occurs with disappearance of atypical bile acids. Differential diagnosis Differential diagnoses include progressive familial intrahepatic cholestasis, diseases that present with neonatal cholestasis, which includes alpha-1-antitrypsin deficiency (ZZ phenotype ), tyrosinemia type 1, biliary atresia, choledochal cyst, cystic fibrosis, Alagille syndrome, galactosemia and hereditary fructose intolerance or diseases that present with growth failure (panhypopituitarism) (see these terms). Antenatal diagnosis Antenatal diagnosis can be established by analysis of embryonic tissue when there has been a previously identified sibling. Urine LSIMS on siblings of affected patients may be performed in the first neonatal days and therapy begun before serious morbidity develops. Management and treatment Treatment is based on oral bile acid therapy, which leads to gradual resolution of biochemical and histologic abnormalities and prevents progression of the disease. Cholic acid therapy creates a pool of bile acids which stimulates bile flow and facilitates fat soluble vitamin absorption and suppresses atypical bile acid synthesis thereby reducing the production of toxic bile acid metabolic intermediates. Ursodeoxycholic acid (UDCA) may be used but is not the therapy of choice because UDCA does not suppress atypical bile acid synthesis and the toxic metabolites that may injure the liver continue to be produced. Prognosis With early treatment, the long-term prognosis is excellent. If a patient is identified with advanced liver disease, cholic acid therapy may not be effective and liver transplantation may be required. Without treatment, the condition is generally fatal.

MalaCards based summary : Bile Acid Synthesis Defect, Congenital, 2, also known as cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency, is related to congenital bile acid synthesis defect and cholestasis, and has symptoms including diarrhea and icterus. An important gene associated with Bile Acid Synthesis Defect, Congenital, 2 is AKR1D1 (Aldo-Keto Reductase Family 1 Member D1), and among its related pathways/superpathways are Synthesis of bile acids and bile salts and Nuclear Receptor transcription pathway. Affiliated tissues include liver and heart, and related phenotypes are splenomegaly and hepatomegaly

Disease Ontology : 12 A congenital bile acid synthesis defect characterized by rapid progession of severe cholestatic liver disease, decreased levels of chenodeoxycholic acid and cholic acid in the serum and urine, and malabsorption of fat and fat-soluble vitamins that has material basis in homozygous or compound heterozygous mutation in the AKR1D1 gene on chromosome 7q33.

MedlinePlus Genetics : 43 Congenital bile acid synthesis defect type 2 is a disorder characterized by cholestasis, a condition that impairs the production and release of a digestive fluid called bile from liver cells. Bile is used during digestion to absorb fats and fat-soluble vitamins, such as vitamins A, D, E, and K. People with congenital bile acid synthesis defect type 2 cannot produce (synthesize) bile acids, which are a component of bile that stimulate bile flow and help it absorb fats and fat-soluble vitamins. As a result, an abnormal form of bile is produced.The signs and symptoms of congenital bile acid synthesis defect type 2 often develop in infancy. Affected infants usually have a failure to gain weight and grow at the expected rate (failure to thrive) and yellowing of the skin and eyes (jaundice) due to impaired bile flow and a buildup of partially formed bile. Excess fat in the feces (steatorrhea) is another feature of congenital bile acid synthesis defect type 2. As the condition progresses, affected individuals can develop liver abnormalities including inflammation or chronic liver disease (cirrhosis). Some individuals with congenital bile acid synthesis defect type 2 cannot absorb certain fat-soluble vitamins, which can result in softening and weakening of the bones (rickets) or problems with blood clotting that lead to prolonged bleeding.If left untreated, congenital bile acid synthesis defect type 2 typically leads to cirrhosis and death in childhood.

UniProtKB/Swiss-Prot : 72 Congenital bile acid synthesis defect 2: A condition characterized by jaundice, intrahepatic cholestasis and hepatic failure. Patients with this liver disease show absence or low levels of chenodeoxycholic acid and cholic acid in plasma and urine.

More information from OMIM: 235555 PS607765

Related Diseases for Bile Acid Synthesis Defect, Congenital, 2

Diseases in the Disorder of Bile Acid Synthesis family:

Bile Acid Synthesis Defect, Congenital, 4 Bile Acid Synthesis Defect, Congenital, 2
Bile Acid Synthesis Defect, Congenital, 1 Bile Acid Synthesis Defect, Congenital, 3
Bile Acid Synthesis Defect, Congenital, 5 Bile Acid Synthesis Defect, Congenital, 6
Congenital Bile Acid Synthesis Defect

Diseases related to Bile Acid Synthesis Defect, Congenital, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 50)
# Related Disease Score Top Affiliating Genes
1 congenital bile acid synthesis defect 32.5 HSD3B7 AKR1D1
2 cholestasis 28.5 SLC51B SLC10A1 NR1I3 NR1I2 NR1H4 NR0B2
3 cholestasis-lymphedema syndrome 10.3 HSD3B7 AKR1D1
4 familial intrahepatic cholestasis 10.3 NR1H4 ABCB11
5 pericholangitis 10.3 SLC10A1 ABCB11
6 bile acid synthesis defect, congenital, 3 10.3 HSD3B7 AKR1D1
7 atp8b1 deficiency 10.2 NR1H4 ABCB11
8 autosomal recessive disease 10.2
9 citrullinemia, type ii, adult-onset 10.2 HSD3B7 ABCB11
10 cholestasis, progressive familial intrahepatic, 4 10.2 NR1H4 ABCB11
11 albinism, oculocutaneous, type v 10.2 SLC45A2 NR1H4
12 alpha-methylacyl-coa racemase deficiency 10.1 SLC45A2 AKR1D1
13 biliary atresia 10.1 SLC10A1 NR1H4 ABCB11
14 bile reflux 10.1 NR1H4 GPBAR1
15 choline deficiency disease 10.1 NR1H4 GPBAR1
16 gallbladder disease 9.9 NR1H4 CYP7A1 ABCB11
17 liver benign neoplasm 9.9 NR1I3 NR1I2
18 pseudohermaphroditism 9.9 NR3C1 HSD3B1 AKR1C2
19 functional diarrhea 9.9 NR1H4 GPBAR1 CYP7A1
20 46,xy sex reversal 9.9 NR0B2 HSD3B1 AKR1C2
21 46,xy sex reversal 2 9.9 NR0B2 HSD3B1
22 crigler-najjar syndrome, type i 9.9 NR1I3 NR1I2 ABCB11
23 cholestasis, progressive familial intrahepatic, 5 9.8 NR1I3 NR1H4 NR0B2 ABCB11
24 steroid inherited metabolic disorder 9.8 NR3C2 HSD3B1
25 xanthomatosis 9.8 NR1I2 NR1H4 CYP7A1
26 acute porphyria 9.7 NR3C1 NR1I3 NR1I2
27 cholangitis 9.7 NR1I2 NR1H4 GPBAR1 ABCB11
28 cholestasis, benign recurrent intrahepatic, 2 9.7 SLC51B SLC10A1 NR1H4 CYP7A1 ABCB11
29 cholestasis, intrahepatic, of pregnancy, 1 9.7 NR1I3 NR1I2 NR1H4 ABCB11
30 extrahepatic cholestasis 9.7 SLC51B SLC10A1 NR1H4 CYP7A1 ABCB11
31 cholestasis, progressive familial intrahepatic, 3 9.7 SLC51B SLC10A1 NR1H4 CYP7A1 ABCB11
32 amelogenesis imperfecta, type ig 9.7 NR3C1 NR1I2 HSD3B1
33 sclerosing cholangitis 9.7 NR1I2 NR1H4 GPBAR1 ABCB11
34 cerebrotendinous xanthomatosis 9.6 NR1I2 NR1H4 HSD3B7 CYP7A1
35 apparent mineralocorticoid excess 9.6 NR3C2 NR3C1
36 liver disease 9.5 SLC10A1 NR1I2 NR1H4 HSD3B7 AKR1D1 ABCB11
37 intrahepatic cholestasis of pregnancy 9.5 NR1I3 NR1I2 NR1H4 GPBAR1 ABCB11
38 cholestasis, progressive familial intrahepatic, 2 9.5 SLC51B SLC10A1 NR1H4 NR0B2 CYP7A1 ABCB11
39 cholestasis, progressive familial intrahepatic, 1 9.5 SLC51B SLC10A1 NR1H4 NR0B2 CYP7A1 ABCB11
40 progressive familial intrahepatic cholestasis 9.5 SLC51B SLC10A1 NR1H4 NR0B2 CYP7A1 ABCB11
41 amelogenesis imperfecta 9.3 NR3C1 NR1I3 NR1I2 NR0B2 HSD3B1
42 heart defects, congenital, and other congenital anomalies 9.3 SLC51B SLC10A1 NR1H4 NR0B2 GPBAR1 CYP7A1
43 primary biliary cholangitis 9.2 NR1I3 NR1I2 NR1H4 GPBAR1 CYP7A1 ABCB11
44 bilirubin metabolic disorder 9.2 SLC10A1 NR1I3 NR1I2 NR1H4 HSD3B7 CYP7A1
45 cholestasis, benign recurrent intrahepatic, 1 9.1 SLC51B SLC10A1 NR1I2 NR1H4 NR0B2 CYP7A1
46 cholangitis, primary sclerosing 9.1 SLC10A1 NR1I2 NR1H4 NR0B2 GPBAR1 CYP7A1
47 bile duct disease 8.9 SLC51B SLC10A1 NR1I2 NR1H4 NR0B2 GPBAR1
48 body mass index quantitative trait locus 11 8.8 NR3C2 NR3C1 NR1I3 NR1H4 NR0B2 GPBAR1
49 biliary tract disease 8.7 SLC51B SLC10A1 NR1I3 NR1I2 NR1H4 NR0B2
50 leber plus disease 8.6 SLC51B SLC10A1 NR1I3 NR1I2 NR1H4 NR0B2

Graphical network of the top 20 diseases related to Bile Acid Synthesis Defect, Congenital, 2:



Diseases related to Bile Acid Synthesis Defect, Congenital, 2

Symptoms & Phenotypes for Bile Acid Synthesis Defect, Congenital, 2

Human phenotypes related to Bile Acid Synthesis Defect, Congenital, 2:

58 31 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 splenomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001744
2 hepatomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002240
3 malabsorption 58 31 hallmark (90%) Very frequent (99-80%) HP:0002024
4 elevated hepatic transaminase 58 31 hallmark (90%) Very frequent (99-80%) HP:0002910
5 jaundice 58 31 hallmark (90%) Very frequent (99-80%) HP:0000952
6 biliary tract abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0001080
7 neonatal cholestatic liver disease 58 31 hallmark (90%) Very frequent (99-80%) HP:0006566
8 cirrhosis 58 31 frequent (33%) Frequent (79-30%) HP:0001394
9 abnormal bleeding 58 31 frequent (33%) Frequent (79-30%) HP:0001892
10 chronic hepatic failure 58 31 frequent (33%) Frequent (79-30%) HP:0100626
11 osteoporosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000939
12 failure to thrive 31 HP:0001508
13 hepatic failure 31 HP:0001399
14 steatorrhea 31 HP:0002570
15 hyperbilirubinemia 31 HP:0002904
16 diarrhea 31 HP:0002014
17 intrahepatic cholestasis 31 HP:0001406
18 elevated alkaline phosphatase 31 HP:0003155
19 abnormality of the coagulation cascade 31 HP:0003256

Symptoms via clinical synopsis from OMIM®:

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

Abdomen Liver:
hepatomegaly
jaundice
intrahepatic cholestasis
giant cell transformation on biopsy
canalicular cholestasis
more
Abdomen Gastrointestinal:
steatorrhea
diarrhea
malabsorption of fat and fat-soluble vitamins

Hematology:
coagulopathy secondary to liver disease

Abdomen Spleen:
splenomegaly

Skin Nails Hair Skin:
jaundice

Laboratory Abnormalities:
hyperbilirubinemia
increased serum alkaline phosphatase
abnormal liver function tests
normal serum levels of gamma-ggt
decreased or absent serum and urinary chenodeoxycholic acid and cholic acid

Clinical features from OMIM®:

235555 (Updated 20-May-2021)

UMLS symptoms related to Bile Acid Synthesis Defect, Congenital, 2:


diarrhea; icterus

GenomeRNAi Phenotypes related to Bile Acid Synthesis Defect, Congenital, 2 according to GeneCards Suite gene sharing:

26 (show all 40)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-105 10.13 NR1I2
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-134 10.13 NR1I2
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-135 10.13 NR1I2
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 10.13 NR1I2
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-140 10.13 NR1I2
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 10.13 NR3C2
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-15 10.13 AKR1D1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-16 10.13 NR1H4
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-168 10.13 NR1I2
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-185 10.13 NR3C2
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-198 10.13 NR3C2
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-200 10.13 AKR1D1
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-202 10.13 AKR1D1
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-203 10.13 AKR1D1
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-27 10.13 NR3C2
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-47 10.13 AKR1D1
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 10.13 NR1H4
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-70 10.13 NR3C2
19 Decreased shRNA abundance (Z-score < -2) GR00366-A-90 10.13 NR1I2
20 Increased shRNA abundance (Z-score > 2) GR00366-A-111 9.96 NR3C1
21 Increased shRNA abundance (Z-score > 2) GR00366-A-114 9.96 NR1I2
22 Increased shRNA abundance (Z-score > 2) GR00366-A-136 9.96 GPBAR1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-14 9.96 NR3C1
24 Increased shRNA abundance (Z-score > 2) GR00366-A-144 9.96 GPBAR1
25 Increased shRNA abundance (Z-score > 2) GR00366-A-157 9.96 NR3C1
26 Increased shRNA abundance (Z-score > 2) GR00366-A-172 9.96 NR1I2
27 Increased shRNA abundance (Z-score > 2) GR00366-A-18 9.96 NR3C1
28 Increased shRNA abundance (Z-score > 2) GR00366-A-184 9.96 NR1I2
29 Increased shRNA abundance (Z-score > 2) GR00366-A-190 9.96 NR1I2
30 Increased shRNA abundance (Z-score > 2) GR00366-A-191 9.96 NR1I2
31 Increased shRNA abundance (Z-score > 2) GR00366-A-209 9.96 GPBAR1
32 Increased shRNA abundance (Z-score > 2) GR00366-A-21 9.96 NR3C1
33 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.96 NR3C1
34 Increased shRNA abundance (Z-score > 2) GR00366-A-24 9.96 GPBAR1
35 Increased shRNA abundance (Z-score > 2) GR00366-A-53 9.96 NR1I2
36 Increased shRNA abundance (Z-score > 2) GR00366-A-57 9.96 GPBAR1
37 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.96 GPBAR1
38 Increased shRNA abundance (Z-score > 2) GR00366-A-79 9.96 NR3C1
39 Increased shRNA abundance (Z-score > 2) GR00366-A-84 9.96 GPBAR1
40 shRNA abundance <= 50% GR00343-S 9.1 GPBAR1 HSD3B1 HSD3B7 NR1I2 SLC10A1 SLC45A2

MGI Mouse Phenotypes related to Bile Acid Synthesis Defect, Congenital, 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.9 ABCB11 CYP7A1 GPBAR1 HSD3B7 NR0B2 NR1H4
2 homeostasis/metabolism MP:0005376 9.73 ABCB11 CYP7A1 GPBAR1 HSD3B7 NR0B2 NR1H4
3 liver/biliary system MP:0005370 9.28 ABCB11 CYP7A1 GPBAR1 HSD3B7 NR0B2 NR1H4

Drugs & Therapeutics for Bile Acid Synthesis Defect, Congenital, 2

Search Clinical Trials , NIH Clinical Center for Bile Acid Synthesis Defect, Congenital, 2

Cochrane evidence based reviews: bile acid synthesis defect, congenital, 2

Genetic Tests for Bile Acid Synthesis Defect, Congenital, 2

Genetic tests related to Bile Acid Synthesis Defect, Congenital, 2:

# Genetic test Affiliating Genes
1 Congenital Bile Acid Synthesis Defect 2 29 AKR1D1

Anatomical Context for Bile Acid Synthesis Defect, Congenital, 2

MalaCards organs/tissues related to Bile Acid Synthesis Defect, Congenital, 2:

40
Liver, Heart

Publications for Bile Acid Synthesis Defect, Congenital, 2

Articles related to Bile Acid Synthesis Defect, Congenital, 2:

(show all 11)
# Title Authors PMID Year
1
Characterization of disease-related 5beta-reductase (AKR1D1) mutations reveals their potential to cause bile acid deficiency. 6 57
20522910 2010
2
SRD5B1 (AKR1D1) gene analysis in delta(4)-3-oxosteroid 5beta-reductase deficiency: evidence for primary genetic defect. 57 6
15030995 2004
3
Mutations in SRD5B1 (AKR1D1), the gene encoding delta(4)-3-oxosteroid 5beta-reductase, in hepatitis and liver failure in infancy. 57 6
12970144 2003
4
Delta 4-3-oxosteroid 5 beta-reductase deficiency: failure of ursodeoxycholic acid treatment and response to chenodeoxycholic acid plus cholic acid. 6 57
8707100 1996
5
Diagnosis of the first Japanese patient with 3-oxo-delta4-steroid 5beta-reductase deficiency by use of immunoblot analysis. 57
9625335 1998
6
Abnormal bile acid metabolism and neonatal hemochromatosis: a subset with poor prognosis. 57
9285385 1997
7
Gene analysis in delta 4-3-oxosteroid 5 beta-reductase deficiency. 57
9024384 1997
8
Delta 4-3-oxosteroid 5 beta-reductase deficiency causing neonatal liver failure and hemochromatosis. 57
8301429 1994
9
Resolution of liver biopsy alterations in three siblings with bile acid treatment of an inborn error of bile acid metabolism (delta 4-3-oxosteroid 5 beta-reductase deficiency). 57
8225213 1993
10
Delta 4-3-oxosteroid 5 beta-reductase deficiency described in identical twins with neonatal hepatitis. A new inborn error in bile acid synthesis. 57
3198770 1988
11
[Clinical feature and genetic analysis of a family affected by congenital bile acid synthesis defect type 2: identification of 2 novel mutations in AKR1D1 gene]. 61
28697823 2017

Variations for Bile Acid Synthesis Defect, Congenital, 2

ClinVar genetic disease variations for Bile Acid Synthesis Defect, Congenital, 2:

6 (show top 50) (show all 108)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 AKR1D1 NM_005989.4(AKR1D1):c.593C>T (p.Pro198Leu) SNV Pathogenic 5374 rs121918342 GRCh37: 7:137791367-137791367
GRCh38: 7:138106621-138106621
2 AKR1D1 AKR1D1, 1-BP DEL, 511T Deletion Pathogenic 5375 GRCh37:
GRCh38:
3 AKR1D1 NM_005989.4(AKR1D1):c.316C>T (p.Leu106Phe) SNV Pathogenic 5376 rs121918343 GRCh37: 7:137776568-137776568
GRCh38: 7:138091822-138091822
4 AKR1D1 NM_005989.4(AKR1D1):c.398C>G (p.Pro133Arg) SNV Pathogenic 5377 rs267606649 GRCh37: 7:137782631-137782631
GRCh38: 7:138097885-138097885
5 AKR1D1 NM_005989.4(AKR1D1):c.781C>T (p.Arg261Cys) SNV Pathogenic 5378 rs267606650 GRCh37: 7:137792252-137792252
GRCh38: 7:138107506-138107506
6 AKR1D1 NM_005989.4(AKR1D1):c.267G>A (p.Trp89Ter) SNV Pathogenic 915290 GRCh37: 7:137776519-137776519
GRCh38: 7:138091773-138091773
7 AKR1D1 NM_005989.4(AKR1D1):c.796C>T (p.Arg266Ter) SNV Pathogenic 915331 GRCh37: 7:137792267-137792267
GRCh38: 7:138107521-138107521
8 AKR1D1 NM_005989.4(AKR1D1):c.332T>C (p.Leu111Pro) SNV Likely pathogenic 594766 rs187887082 GRCh37: 7:137776584-137776584
GRCh38: 7:138091838-138091838
9 AKR1D1 NM_005989.4(AKR1D1):c.797G>A (p.Arg266Gln) SNV Likely pathogenic 1064451 GRCh37: 7:137792268-137792268
GRCh38: 7:138107522-138107522
10 AKR1D1 NM_005989.4(AKR1D1):c.509A>G (p.Asn170Ser) SNV Uncertain significance 1030985 GRCh37: 7:137790105-137790105
GRCh38: 7:138105359-138105359
11 AKR1D1 NM_005989.4(AKR1D1):c.647T>C (p.Ile216Thr) SNV Uncertain significance 1030986 GRCh37: 7:137791421-137791421
GRCh38: 7:138106675-138106675
12 AKR1D1 NM_005989.4(AKR1D1):c.675T>A (p.Ser225Arg) SNV Uncertain significance 1030987 GRCh37: 7:137791449-137791449
GRCh38: 7:138106703-138106703
13 AKR1D1 NM_005989.4(AKR1D1):c.*1124A>G SNV Uncertain significance 910282 GRCh37: 7:137802532-137802532
GRCh38: 7:138117786-138117786
14 AKR1D1 NM_005989.4(AKR1D1):c.*1139G>T SNV Uncertain significance 910283 GRCh37: 7:137802547-137802547
GRCh38: 7:138117801-138117801
15 AKR1D1 NM_005989.4(AKR1D1):c.*1435G>A SNV Uncertain significance 910340 GRCh37: 7:137802843-137802843
GRCh38: 7:138118097-138118097
16 AKR1D1 NM_005989.4(AKR1D1):c.*1559A>T SNV Uncertain significance 910341 GRCh37: 7:137802967-137802967
GRCh38: 7:138118221-138118221
17 AKR1D1 NM_005989.4(AKR1D1):c.*1631A>C SNV Uncertain significance 910342 GRCh37: 7:137803039-137803039
GRCh38: 7:138118293-138118293
18 AKR1D1 NM_005989.4(AKR1D1):c.-26T>G SNV Uncertain significance 911167 GRCh37: 7:137761239-137761239
GRCh38: 7:138076493-138076493
19 AKR1D1 NM_005989.4(AKR1D1):c.*375A>G SNV Uncertain significance 911240 GRCh37: 7:137801783-137801783
GRCh38: 7:138117037-138117037
20 AKR1D1 NM_005989.4(AKR1D1):c.*421T>C SNV Uncertain significance 911241 GRCh37: 7:137801829-137801829
GRCh38: 7:138117083-138117083
21 AKR1D1 NM_005989.4(AKR1D1):c.195G>A (p.Gly65=) SNV Uncertain significance 911368 GRCh37: 7:137773448-137773448
GRCh38: 7:138088702-138088702
22 AKR1D1 NM_005989.4(AKR1D1):c.297C>T (p.Arg99=) SNV Uncertain significance 911369 GRCh37: 7:137776549-137776549
GRCh38: 7:138091803-138091803
23 AKR1D1 NM_005989.4(AKR1D1):c.392T>A (p.Ile131Lys) SNV Uncertain significance 911370 GRCh37: 7:137782625-137782625
GRCh38: 7:138097879-138097879
24 AKR1D1 NM_005989.4(AKR1D1):c.454G>A (p.Glu152Lys) SNV Uncertain significance 911371 GRCh37: 7:137782687-137782687
GRCh38: 7:138097941-138097941
25 AKR1D1 NM_005989.4(AKR1D1):c.*432A>G SNV Uncertain significance 911441 GRCh37: 7:137801840-137801840
GRCh38: 7:138117094-138117094
26 AKR1D1 NM_005989.4(AKR1D1):c.*537T>C SNV Uncertain significance 911442 GRCh37: 7:137801945-137801945
GRCh38: 7:138117199-138117199
27 AKR1D1 NM_005989.4(AKR1D1):c.*598G>A SNV Uncertain significance 911443 GRCh37: 7:137802006-137802006
GRCh38: 7:138117260-138117260
28 AKR1D1 NM_005989.4(AKR1D1):c.*655T>C SNV Uncertain significance 911444 GRCh37: 7:137802063-137802063
GRCh38: 7:138117317-138117317
29 AKR1D1 NM_005989.4(AKR1D1):c.*667C>T SNV Uncertain significance 911445 GRCh37: 7:137802075-137802075
GRCh38: 7:138117329-138117329
30 AKR1D1 NM_005989.4(AKR1D1):c.*710T>C SNV Uncertain significance 911446 GRCh37: 7:137802118-137802118
GRCh38: 7:138117372-138117372
31 AKR1D1 NM_005989.4(AKR1D1):c.*1173A>C SNV Uncertain significance 911501 GRCh37: 7:137802581-137802581
GRCh38: 7:138117835-138117835
32 AKR1D1 NM_005989.4(AKR1D1):c.*1153C>T SNV Uncertain significance 358980 rs112833888 GRCh37: 7:137802561-137802561
GRCh38: 7:138117815-138117815
33 AKR1D1 NM_005989.4(AKR1D1):c.*1093C>G SNV Uncertain significance 358974 rs12540340 GRCh37: 7:137802501-137802501
GRCh38: 7:138117755-138117755
34 AKR1D1 NM_005989.4(AKR1D1):c.*294C>A SNV Uncertain significance 358960 rs886062005 GRCh37: 7:137801702-137801702
GRCh38: 7:138116956-138116956
35 AKR1D1 NM_005989.4(AKR1D1):c.*373G>A SNV Uncertain significance 358963 rs564875098 GRCh37: 7:137801781-137801781
GRCh38: 7:138117035-138117035
36 AKR1D1 NM_005989.4(AKR1D1):c.21T>G (p.Ser7Arg) SNV Uncertain significance 358952 rs769312349 GRCh37: 7:137761285-137761285
GRCh38: 7:138076539-138076539
37 AKR1D1 NM_005989.4(AKR1D1):c.380C>T (p.Pro127Leu) SNV Uncertain significance 289546 rs140421486 GRCh37: 7:137782613-137782613
GRCh38: 7:138097867-138097867
38 AKR1D1 NM_005989.4(AKR1D1):c.*944T>C SNV Uncertain significance 358969 rs886062008 GRCh37: 7:137802352-137802352
GRCh38: 7:138117606-138117606
39 AKR1D1 NM_005989.4(AKR1D1):c.*1298A>G SNV Uncertain significance 358992 rs886062011 GRCh37: 7:137802706-137802706
GRCh38: 7:138117960-138117960
40 AKR1D1 NM_005989.4(AKR1D1):c.*1185G>A SNV Uncertain significance 358983 rs551510105 GRCh37: 7:137802593-137802593
GRCh38: 7:138117847-138117847
41 AKR1D1 NM_005989.4(AKR1D1):c.*1199T>A SNV Uncertain significance 358984 rs886062010 GRCh37: 7:137802607-137802607
GRCh38: 7:138117861-138117861
42 AKR1D1 NM_005989.4(AKR1D1):c.*298A>G SNV Uncertain significance 358961 rs886062006 GRCh37: 7:137801706-137801706
GRCh38: 7:138116960-138116960
43 AKR1D1 NM_005989.4(AKR1D1):c.*897T>C SNV Uncertain significance 358967 rs886062007 GRCh37: 7:137802305-137802305
GRCh38: 7:138117559-138117559
44 AKR1D1 NM_005989.4(AKR1D1):c.*1282G>A SNV Uncertain significance 358990 rs534922267 GRCh37: 7:137802690-137802690
GRCh38: 7:138117944-138117944
45 AKR1D1 NM_005989.4(AKR1D1):c.446C>T (p.Ala149Val) SNV Uncertain significance 358955 rs202238711 GRCh37: 7:137782679-137782679
GRCh38: 7:138097933-138097933
46 AKR1D1 NM_005989.4(AKR1D1):c.*1091C>T SNV Uncertain significance 358973 rs886062009 GRCh37: 7:137802499-137802499
GRCh38: 7:138117753-138117753
47 AKR1D1 NM_005989.4(AKR1D1):c.*1173A>T SNV Uncertain significance 358982 rs111628978 GRCh37: 7:137802581-137802581
GRCh38: 7:138117835-138117835
48 AKR1D1 NM_005989.4(AKR1D1):c.*1214A>G SNV Uncertain significance 358985 rs758246977 GRCh37: 7:137802622-137802622
GRCh38: 7:138117876-138117876
49 AKR1D1 NM_005989.4(AKR1D1):c.*197G>T SNV Uncertain significance 358959 rs746014627 GRCh37: 7:137801605-137801605
GRCh38: 7:138116859-138116859
50 AKR1D1 NM_005989.4(AKR1D1):c.*1343C>T SNV Uncertain significance 358994 rs150650955 GRCh37: 7:137802751-137802751
GRCh38: 7:138118005-138118005

UniProtKB/Swiss-Prot genetic disease variations for Bile Acid Synthesis Defect, Congenital, 2:

72
# Symbol AA change Variation ID SNP ID
1 AKR1D1 p.Leu106Phe VAR_033007 rs121918343
2 AKR1D1 p.Pro198Leu VAR_033008 rs121918342
3 AKR1D1 p.Pro133Arg VAR_044430 rs267606649
4 AKR1D1 p.Arg261Cys VAR_044431 rs267606650
5 AKR1D1 p.Gly223Glu VAR_081756 rs122891871

Expression for Bile Acid Synthesis Defect, Congenital, 2

Search GEO for disease gene expression data for Bile Acid Synthesis Defect, Congenital, 2.

Pathways for Bile Acid Synthesis Defect, Congenital, 2

GO Terms for Bile Acid Synthesis Defect, Congenital, 2

Cellular components related to Bile Acid Synthesis Defect, Congenital, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin GO:0000785 9.43 NR3C2 NR3C1 NR1I3 NR1I2 NR1H4 NR0B2
2 host cell nucleus GO:0042025 8.8 NR1I3 NR1I2 NR1H4

Biological processes related to Bile Acid Synthesis Defect, Congenital, 2 according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.97 NR3C1 NR1I3 NR1I2 NR1H4 NR0B2
2 oxidation-reduction process GO:0055114 9.95 HSD3B7 HSD3B1 CYP7A1 AKR1D1 AKR1C2
3 response to organic cyclic compound GO:0014070 9.73 SLC10A1 NR0B2 CYP7A1
4 response to ethanol GO:0045471 9.71 SLC10A1 NR0B2 CYP7A1
5 cholesterol homeostasis GO:0042632 9.69 NR1H4 CYP7A1 ABCB11
6 steroid metabolic process GO:0008202 9.65 NR1I2 HSD3B1 CYP7A1 AKR1D1 AKR1C2
7 digestion GO:0007586 9.58 AKR1D1 AKR1C2
8 xenobiotic transport GO:0042908 9.57 NR1I2 ABCB11
9 intracellular receptor signaling pathway GO:0030522 9.54 NR1I3 NR1I2 NR1H4
10 bile acid metabolic process GO:0008206 9.52 NR1H4 ABCB11
11 bile acid signaling pathway GO:0038183 9.5 SLC10A1 NR1H4 CYP7A1
12 intracellular steroid hormone receptor signaling pathway GO:0030518 9.49 NR3C2 NR3C1
13 cholesterol catabolic process GO:0006707 9.48 CYP7A1 AKR1D1
14 C21-steroid hormone metabolic process GO:0008207 9.46 HSD3B1 AKR1D1
15 bile acid biosynthetic process GO:0006699 9.46 HSD3B7 CYP7A1 AKR1D1 ABCB11
16 cellular response to bile acid GO:1903413 9.43 NR1H4 GPBAR1
17 transcription initiation from RNA polymerase II promoter GO:0006367 9.43 NR3C2 NR3C1 NR1I3 NR1I2 NR1H4 NR0B2
18 regulation of bile acid biosynthetic process GO:0070857 9.4 NR1H4 CYP7A1
19 bile acid and bile salt transport GO:0015721 9.1 SLC51B SLC10A1 NR1H4 NR0B2 CYP7A1 ABCB11

Molecular functions related to Bile Acid Synthesis Defect, Congenital, 2 according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 zinc ion binding GO:0008270 9.96 NR3C2 NR3C1 NR1I3 NR1I2 NR1H4
2 DNA-binding transcription factor activity GO:0003700 9.91 NR3C2 NR3C1 NR1I3 NR1I2 NR1H4
3 oxidoreductase activity GO:0016491 9.88 HSD3B7 HSD3B1 CYP7A1 AKR1D1 AKR1C2
4 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.87 NR3C1 NR1I3 NR1I2 NR1H4
5 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.84 NR3C1 NR1I3 NR1I2 NR1H4
6 sequence-specific DNA binding GO:0043565 9.77 NR3C2 NR3C1 NR1I3 NR1I2 NR1H4
7 nuclear receptor binding GO:0016922 9.55 NR1I2 NR1H4
8 retinoid X receptor binding GO:0046965 9.52 NR1H4 NR0B2
9 alditol:NADP+ 1-oxidoreductase activity GO:0004032 9.49 AKR1D1 AKR1C2
10 bile acid binding GO:0032052 9.46 NR1H4 AKR1C2
11 steroid dehydrogenase activity GO:0016229 9.43 AKR1D1 AKR1C2
12 steroid binding GO:0005496 9.43 NR3C2 NR3C1 AKR1D1
13 3-beta-hydroxy-delta5-steroid dehydrogenase activity GO:0003854 9.4 HSD3B7 HSD3B1
14 ketosteroid monooxygenase activity GO:0047086 9.32 AKR1D1 AKR1C2
15 bile acid receptor activity GO:0038181 9.16 NR1H4 GPBAR1
16 bile acid transmembrane transporter activity GO:0015125 9.13 SLC51B SLC10A1 ABCB11
17 nuclear receptor activity GO:0004879 9.02 NR3C2 NR3C1 NR1I3 NR1I2 NR1H4

Sources for Bile Acid Synthesis Defect, Congenital, 2

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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