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CN1
MCID: CRG003
MIFTS: 63

Crigler-Najjar Syndrome, Type I (CN1)

Categories: Blood diseases, Genetic diseases, Liver diseases, Metabolic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Crigler-Najjar Syndrome, Type I

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MalaCards integrated aliases for Crigler-Najjar Syndrome, Type I:

Name: Crigler-Najjar Syndrome, Type I 56 12 52 13 37 39
Crigler-Najjar Syndrome 56 12 74 25 58 36 29 54 6 15 32
Crigler-Najjar Syndrome Type 1 58 29 6
Hereditary Unconjugated Hyperbilirubinemia 25 58
Crigler Najjar Syndrome, Type 1 52 71
Crigler Najjar Syndrome 12 25
Bilirubin Uridinediphosphate Glucuronosyltransferase Deficiency Type 1 58
Bilirubin Uridinediphosphate Glucuronosyltransferase Deficiency 58
Familial Nonhemolytic Unconjugated Hyperbilirubinemia 25
Hyperbilirubinemia, Crigler-Najjar Type I; Hblrcn1 56
Hereditary Unconjugated Hyperbilirubinemia Type 1 58
Bilirubin Udp Glucuronyl Transferase Deficiency 12
Hyperbilirubinemia, Crigler-Najjar Type I 56
Bilirubin-Ugt Deficiency Type 1 58
Crigler-Najjar Syndrome Type I 73
Crigler-Najjar Syndrome 1 73
Bilirubin-Ugt Deficiency 58
Ugt Deficiency Type 1 58
Ugt Deficiency 58
Hblrcn1 56
Cn-I 73
Cn1 73

Characteristics:

Orphanet epidemiological data:

58
crigler-najjar syndrome
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe),1-9/100000 (Europe); Age of onset: Neonatal; Age of death: normal life expectancy;
crigler-najjar syndrome type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

56
Miscellaneous:
very rare
death in infancy secondary to kernicterus
no response to phenobarbital

Inheritance:
autosomal recessive


HPO:

31
crigler-najjar syndrome, type i:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases
Anatomical: Liver diseases Neuronal diseases Blood diseases
See all MalaCards categories (disease lists)
ICD10: 32 33
Orphanet: 58  
Rare hepatic diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:3803
OMIM 56 218800
OMIM Phenotypic Series 56 PS237450
KEGG 36 H02054
NCIt 49 C84656
SNOMED-CT 67 8933000
ICD10 32 E80.5
MESH via Orphanet 44 C536212 D003414
ICD10 via Orphanet 33 E80.5
UMLS via Orphanet 72 C0010324 C2931131
MedGen 41 C0010324
UMLS 71 C0010324
Sources

Summaries for Crigler-Najjar Syndrome, Type I

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Genetics Home Reference : 25 Crigler-Najjar syndrome is a severe condition characterized by high levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin is produced when red blood cells are broken down. This substance is removed from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form of bilirubin (called unconjugated bilirubin) to a nontoxic form called conjugated bilirubin. People with Crigler-Najjar syndrome have a buildup of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia). Bilirubin has an orange-yellow tint, and hyperbilirubinemia causes yellowing of the skin and whites of the eyes (jaundice). In Crigler-Najjar syndrome, jaundice is apparent at birth or in infancy. Severe unconjugated hyperbilirubinemia can lead to a condition called kernicterus, which is a form of brain damage caused by the accumulation of unconjugated bilirubin in the brain and nerve tissues. Babies with kernicterus are often extremely tired (lethargic) and may have weak muscle tone (hypotonia). These babies may experience episodes of increased muscle tone (hypertonia) and arching of their backs. Kernicterus can lead to other neurological problems, including involuntary writhing movements of the body (choreoathetosis), hearing problems, or intellectual disability. Crigler-Najjar syndrome is divided into two types. Type 1 (CN1) is very severe, and affected individuals can die in childhood due to kernicterus, although with proper treatment, they may survive longer. Type 2 (CN2) is less severe. People with CN2 are less likely to develop kernicterus, and most affected individuals survive into adulthood.

MalaCards based summary : Crigler-Najjar Syndrome, Type I, also known as crigler-najjar syndrome, is related to inherited metabolic disorder and crigler-najjar syndrome, type ii. An important gene associated with Crigler-Najjar Syndrome, Type I is UGT1A1 (UDP Glucuronosyltransferase Family 1 Member A1), and among its related pathways/superpathways are Porphyrin and chlorophyll metabolism and Metabolism. The drugs Diazepam and Anesthetics have been mentioned in the context of this disorder. Affiliated tissues include Liver, brain and eye, and related phenotypes are jaundice and prolonged neonatal jaundice

Disease Ontology : 12 A bilirubin metabolic disorder that involves a build up of bilirubin as bilirubin is not being broken down as a result of a lack or deficiency of the enzyme uridine diphosphate glycosyltransferase (UGT).

NIH Rare Diseases : 52 Crigler Najjar syndrome , type 1 is an inherited disorder in which bilirubin , a substance made by the liver, cannot be broken down. This condition occurs when the enzyme that normally converts bilirubin into a form that can easily be removed from the body does not work correctly. Without this enzyme, bilirubin can build up in the body and lead to jaundice and damage to the brain, muscles, and nerves. Crigler Najjar syndrome, type 1 is caused by mutations in the UGT1A1 gene . The condition is inherited in an autosomal recessive manner. Treatment relies on regular phototherapy throughout life. Blood transfusions and calcium compounds have also been used. Liver transplantation may be considered in some individuals.

KEGG : 36 Crigler-Najjar (CN) syndrome is a familial unconjugated hyperbilirubinemia. It is caused by deficiency of bilirubin-UDP-glucuronosyltransferase (UGT1A1) which is involved in the detoxification of bilirubin. There are two forms of CN. CN-1 is characterized by almost complete absence of UGT1A1 enzyme activity. Left untreated, CN-1 almost invariably results in death from bilirubin encephalopathy (kernicterus). CN-2 is characterized by intermediate levels of hyperbilirubinemia, due to a severe, but incomplete lack of UGT1A1 activity.

UniProtKB/Swiss-Prot : 73 Crigler-Najjar syndrome 1: Patients have severe hyperbilirubinemia and usually die of kernicterus (bilirubin accumulation in the basal ganglia and brainstem nuclei) within the first year of life. CN1 inheritance is autosomal recessive.

Wikipedia : 74 Crigler-Najjar syndrome is a rare inherited disorder affecting the metabolism of bilirubin, a chemical... more...

More information from OMIM: 218800 PS237450
Sources

Related Diseases for Crigler-Najjar Syndrome, Type I

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Diseases in the Crigler-Najjar Syndrome, Type I family:

Crigler-Najjar Syndrome, Type Ii

Diseases related to Crigler-Najjar Syndrome, Type I via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 78)
# Related Disease Score Top Affiliating Genes
1 inherited metabolic disorder 30.5 UGT1A8 UGT1A6 UGT1A1
2 crigler-najjar syndrome, type ii 30.0 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
3 gilbert syndrome 30.0 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
4 kernicterus 29.3 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A1
5 bilirubin metabolic disorder 28.0 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
6 bilirubin, serum level of, quantitative trait locus 1 27.7 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
7 olfactory nerve disease 11.3
8 porphyria 10.7
9 cholestasis 10.6
10 autosomal recessive disease 10.6
11 liver disease 10.6
12 hemophilia 10.6
13 congenital nonhemolytic jaundice 10.6
14 hyperbilirubinemia, transient familial neonatal 10.5
15 branchiootic syndrome 1 10.5
16 hepatitis 10.5
17 neonatal jaundice 10.5
18 tremor 10.5
19 ataxia and polyneuropathy, adult-onset 10.3
20 severe combined immunodeficiency 10.3
21 encephalopathy 10.3
22 spasticity 10.3
23 pfeiffer syndrome 10.3
24 hypercholesterolemia, familial, 1 10.3
25 otitis media 10.3
26 hemophilia a 10.3
27 ichthyosis, x-linked 10.3
28 kearns-sayre syndrome 10.3
29 gallbladder disease 1 10.3
30 beta-thalassemia 10.3
31 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 10.3
32 x-linked recessive disease 10.3
33 thalassemia 10.3
34 portal vein thrombosis 10.3
35 hepatitis a 10.3
36 hepatic coma 10.3
37 hereditary spherocytosis 10.3
38 hepatic encephalopathy 10.3
39 familial hypercholesterolemia 10.3
40 acute cholangitis 10.3
41 ichthyosis 10.3
42 cholecystitis 10.3
43 cerebral palsy 10.3
44 gastroenteritis 10.3
45 acute kidney failure 10.3
46 liver cirrhosis 10.3
47 dystonia 10.3
48 kidney disease 10.3
49 appendicitis 10.3
50 cholangitis 10.3

Graphical network of the top 20 diseases related to Crigler-Najjar Syndrome, Type I:



Diseases related to Crigler-Najjar Syndrome, Type I
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Symptoms & Phenotypes for Crigler-Najjar Syndrome, Type I

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Human phenotypes related to Crigler-Najjar Syndrome, Type I:

58 31 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 jaundice 58 31 hallmark (90%) Very frequent (99-80%) HP:0000952
2 prolonged neonatal jaundice 58 31 hallmark (90%) Very frequent (99-80%) HP:0006579
3 biliary tract abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0001080
4 kernicterus 58 31 hallmark (90%) Very frequent (99-80%) HP:0001343
5 neonatal hyperbilirubinemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003265
6 unconjugated hyperbilirubinemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008282
7 infantile muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008947
8 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
9 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0000365
10 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
11 delayed speech and language development 58 31 occasional (7.5%) Occasional (29-5%) HP:0000750
12 tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0001337
13 memory impairment 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0002354
14 vertigo 58 31 occasional (7.5%) Occasional (29-5%) HP:0002321
15 ophthalmoparesis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000597
16 lethargy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001254
17 encephalitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002383
18 oculomotor nerve palsy 58 31 occasional (7.5%) Occasional (29-5%) HP:0012246
19 seizure 31 occasional (7.5%) HP:0001250
20 seizures 58 Occasional (29-5%),Occasional (29-5%)
21 cognitive impairment 58 Occasional (29-5%)
22 abnormality of the liver 58 Very frequent (99-80%),Very frequent (99-80%)
23 encephalopathy 31 HP:0001298

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
kernicterus
bilirubin encephalopathy

Laboratory Abnormalities:
hyperbilirubinemia, unconjugated, 20-30mg/dl
absence of hepatic udp-glucuronyl-transferase
normal liver histology
normal liver function tests

Skin Nails Hair Skin:
jaundice, congenital nonhemolytic

Clinical features from OMIM:

218800

GenomeRNAi Phenotypes related to Crigler-Najjar Syndrome, Type I according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-14 9.32 UGT1A4
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-147 9.32 UGT1A3 UGT1A7
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.32 UGT1A7
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-20 9.32 UGT1A4 UGT1A7
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-200 9.32 UGT1A3 UGT1A4
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-211 9.32 UGT1A3 UGT1A4
Sources

Drugs & Therapeutics for Crigler-Najjar Syndrome, Type I

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Drugs for Crigler-Najjar Syndrome, Type I (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 24)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Diazepam Approved, Illicit, Investigational, Vet_approved Phase 4 439-14-5 3016
2 Anesthetics Phase 4
3 Hypnotics and Sedatives Phase 4
4 Psychotropic Drugs Phase 4
5 Anti-Anxiety Agents Phase 4
6 Anesthetics, General Phase 4
7 GABA Modulators Phase 4
8 Antiemetics Phase 4
9 Anesthetics, Intravenous Phase 4
10 Neurotransmitter Agents Phase 4
11 Gastrointestinal Agents Phase 4
12 Anticonvulsants Phase 4
13
carbamide peroxide Approved Phase 1 124-43-6
14
Ornithine Approved, Nutraceutical Phase 1 70-26-8, 3184-13-2 6262
15 Liver Extracts Phase 1
16
Acetylcholine Approved, Investigational 51-84-3 187
17
Orlistat Approved, Investigational 96829-58-2 3034010
18 abobotulinumtoxinA
19 Cholinergic Agents
20 Botulinum Toxins
21 Botulinum Toxins, Type A
22 Anti-Obesity Agents
23 Lipid Regulating Agents
24
Bilirubin 69853-43-6, 635-65-4 21252250 5280352

Interventional clinical trials:

(show all 14)
# Name Status NCT ID Phase Drugs
1 Rectal Versus Oral Diazepam Administration in the Treatment of Levator Ani Syndrome in Participants Who Have Not Responded to Physical Therapy Treatment: A Prospective Randomized Study Recruiting NCT04216797 Phase 4 Diazepam Tablets
2 A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Promethera HepaStem in Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN) Paediatric Patients. Completed NCT01765283 Phase 1, Phase 2
3 VALENS: A Phase 1/2, Randomized, Open-Label, Ascending-Dose, Delayed-Treatment Concurrent Control Clinical Study to Evaluate the Safety and Preliminary Efficacy of AT342, an AAV8-Delivered Gene Transfer Therapy in Crigler-Najjar Syndrome Subjects Aged 1 Year and Older Suspended NCT03223194 Phase 1, Phase 2
4 In-Vitro Transdifferentiation of Mesenchymal Stem Cells to Hepatocytes and Allogenic Transplantation of Hepatocytes to the Patients With Homozygous Familial Hypercholesterolemia Completed NCT00515307 Phase 1
5 Hepatocyte Transplantation for Liver Based Metabolic Disorders Suspended NCT01345578 Phase 1 human hepatocyte transplantation
6 Trial of a New Phototherapy Device for Treating Hyperbilirubinemia in Crigler-Najjar Patients : a New Concept Unknown status NCT02356978
7 Comparison of Biofeedback Therapy and Botulinum Toxin Type A Injections for Treatment of Painful Levator Ani Syndrome in Women: A Randomized, Prospective Trial Unknown status NCT00564707
8 Establishing Novel Detection Techniques for Various Genetic-Related Diseases by Applying DHPLC Platform. Unknown status NCT00154960
9 LUSTRO: A Clinical Assessment Study in Crigler-Najjar Syndrome Completed NCT03078881
10 Study of the Prevalence of Pre-existing Immunity Against the Adeno-associated Virus (AAV) in Patients With Crigler-Najjar Syndrome Completed NCT02302690
11 Long-term Safety Follow-up Study of Patients Having Received Infusions of HepaStem Completed NCT02051049
12 Orlistat Treatment of Unconjugated Hyperbilirubinemia in Crigler-Najjar Disease; A Randomized Controlled Trial Completed NCT00461799 orlistat
13 A Phase I/II, Open Label, Escalating Dose Study to Evaluate Safety and Efficacy of an Intravenous Injection of GNT0003 (AAV Vector Expressing the UGT1A1 Transgene) in Patients With Severe Crigler-Najjar Syndrome Requiring Phototherapy Recruiting NCT03466463
14 HepaStem Long-Term Safety Registry - Registry for Patients Who Have Been Administered HepaStem Enrolling by invitation NCT03343756

Search NIH Clinical Center for Crigler-Najjar Syndrome, Type I

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Read about Crigler-Najjar Syndrome, Type I cell therapies at LifeMap Discovery.
Stem-cell-based therapeutic approaches for Crigler-Najjar Syndrome, Type I:
Hepatocyte transplantation for treatment of liver disorders
Hepatocyte transplantation for treatment of liver failure and inherited metabolic diseases
Promethera HepaStem, human adult liver progenitor cells for liver diseases
Embryonic/Adult Cultured Cells Related to Crigler-Najjar Syndrome, Type I:
Hepatocytes PMIDs: 12777539 22167636 22789058 9580649 15239608
Adult liver progenitor cells PMIDs: 22525602 23211283 24142276 22900053 19091822
Sources

Genetic Tests for Crigler-Najjar Syndrome, Type I

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Genetic tests related to Crigler-Najjar Syndrome, Type I:

# Genetic test Affiliating Genes
1 Crigler-Najjar Syndrome 29
2 Crigler-Najjar Syndrome Type 1 29 UGT1A1
Sources

Anatomical Context for Crigler-Najjar Syndrome, Type I

About this section

MalaCards organs/tissues related to Crigler-Najjar Syndrome, Type I:

40
Liver, Brain, Eye, Skin, Testes, Thymus, Heart
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Crigler-Najjar Syndrome, Type I:
# Tissue Anatomical CompartmentCell Relevance
1 Liver Liver Lobule Hepatocytes Affected by disease, potential therapeutic candidate
Sources

Publications for Crigler-Najjar Syndrome, Type I

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Articles related to Crigler-Najjar Syndrome, Type I:

(show top 50) (show all 437)
# Title Authors PMID Year
1
Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2. 6 56 61
8276413 1993
2
Identification of a genetic alteration in the code for bilirubin UDP-glucuronosyltransferase in the UGT1 gene complex of a Crigler-Najjar type I patient. 61 6 56
1634606 1992
3
Prolonged survival in three brothers with severe type 2 Crigler-Najjar syndrome. Ultrastructural and metabolic studies. 61 56 6
805737 1975
4
Co-occurrence of three different mutations in the bilirubin UDP-glucuronosyltransferase gene in a Chinese family with Crigler-Najjar syndrome type I and Gilbert's syndrome. 6 54 61
14616765 2003
5
Rapid proteasomal degradation of translocation-deficient UDP-glucuronosyltransferase 1A1 proteins in patients with Crigler-Najjar type II. 6 61 54
14550264 2003
6
Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate- glucuronosyltransferase gene. 6 61 54
11061796 2000
7
Molecular analysis of patients of Sardinian descent with Crigler-Najjar syndrome type I. 6 54 61
9039987 1997
8
A new type of defect in the gene for bilirubin uridine 5'-diphosphate-glucuronosyltransferase in a patient with Crigler-Najjar syndrome type I. 54 61 6
7936809 1994
9
Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I. 61 54 6
1634050 1992
10
Immunochemical analysis of uridine diphosphate-glucuronosyltransferase in four patients with the Crigler-Najjar syndrome type I. 61 56 54
2108190 1990
11
Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates. 61 6
18004206 2007
12
Paternal isodisomy for chromosome 2 as the cause of Crigler-Najjar type I syndrome. 6 61
15586176 2005
13
Crigler-Najjar syndrome type I in Tunisia may be associated with a founder effect related to the Q357R mutation within the UGT1 gene. 61 6
11968090 2002
14
Neurologic perspectives of Crigler-Najjar syndrome type I. 61 56
9660509 1998
15
Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. 61 56
9580649 1998
16
Splice-site mutations: a novel genetic mechanism of Crigler-Najjar syndrome type 1. 6 61
9497253 1998
17
Analysis of bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II. 6 61
9621515 1998
18
A neurophysiological study in children and adolescents with Crigler-Najjar syndrome type I. 61 56
9413009 1997
19
Current therapy for Crigler-Najjar syndrome type 1: report of a world registry. 61 56
8690398 1996
20
The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. 6 61
7565971 1995
21
A mutation in bilirubin uridine 5'-diphosphate-glucuronosyltransferase isoform 1 causing Crigler-Najjar syndrome type II. 61 6
8514037 1993
22
Investigation of the molecular basis of the genetic deficiency of UDP-glucuronosyltransferase in Crigler-Najjar syndrome. 56 61
1749222 1991
23
Crigler-Najjar syndrome type I: treatment by home phototherapy followed by orthotopic hepatic transplantation. 56 61
3546653 1987
24
Clinical conference. Crigler-Najjar syndrome (type I) in an adult male. 61 56
422012 1979
25
Association of polymorphisms in four bilirubin metabolism genes with serum bilirubin in three Asian populations. 6
19243019 2009
26
Molecular pathogenesis of Gilbert's syndrome: decreased TATA-binding protein binding affinity of UGT1A1 gene promoter. 6
17496722 2007
27
Global gene expression as a function of germline genetic variation. 6
15857854 2005
28
Hyperbilirubinemia in homozygous HbE disease is associated with the UGT1A1 gene polymorphism. 6
16114182 2005
29
Pharmacogenetics and drug development: the path to safer and more effective drugs. 6
15372086 2004
30
UDP-glucuronosyltransferase 1 gene promoter polymorphism is associated with increased serum bilirubin levels and cholecystectomy in patients with sickle cell anemia. 6
12859413 2003
31
The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): hematologic and evolutionary implications. 6
12850492 2003
32
Association of a homozygous (TA)8 promoter polymorphism and a N400D mutation of UGT1A1 in a child with Crigler-Najjar type II syndrome. 6
12402338 2002
33
Genetic determinants of jaundice and gallstones in haemoglobin E beta thalassaemia. 6
11425418 2001
34
Interaction of coding region mutations and the Gilbert-type promoter abnormality of the UGT1A1 gene causes moderate degrees of unconjugated hyperbilirubinaemia and may lead to neonatal kernicterus. 6
11370628 2001
35
Molecular diagnosis of a familial nonhemolytic hyperbilirubinemia (Gilbert's syndrome) in healthy subjects. 6
11003624 2000
36
Gilbert's syndrome and hyperbilirubinaemia in ABO-incompatible neonates. 6
10968441 2000
37
Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn. 6
10190918 1999
38
Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? 6
9653159 1998
39
UGT1 promoter polymorphism accounts for increased neonatal appearance of hereditary spherocytosis. 6
9446675 1998
40
Hyperbilirubinaemia in heterozygous beta-thalassaemia is related to co-inherited Gilbert's syndrome. 6
9375768 1997
41
The expression of uridine diphosphate glucuronosyltransferase gene is a major determinant of bilirubin level in heterozygous beta-thalassaemia and in glucose-6-phosphate dehydrogenase deficiency. 6
9375769 1997
42
Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia. 6
9342374 1997
43
Induction of central tolerance by intrathymic inoculation of adenoviral antigens into the host thymus permits long-term gene therapy in Gunn rats. 56
8958229 1996
44
A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II. 6
8706880 1996
45
Gilbert's syndrome is caused by a heterozygous missense mutation in the gene for bilirubin UDP-glucuronosyltransferase. 6
8528206 1995
46
Identification of two single base substitutions in the UGT1 gene locus which abolish bilirubin uridine diphosphate glucuronosyltransferase activity in vitro. 6
7906695 1994
47
A phenylalanine codon deletion at the UGT1 gene complex locus of a Crigler-Najjar type I patient generates a pH-sensitive bilirubin UDP-glucuronosyltransferase. 6
8226884 1993
48
New developments in glucuronidation research: report of a workshop on "glucuronidation, its role in health and disease". 56
1531971 1992
49
Suppression of bilirubin production in the Crigler-Najjar type I syndrome: studies with the heme oxygenase inhibitor tin-mesoporphyrin. 56
1734381 1992
50
Molecular basis of multiple UDP-glucuronosyltransferase isoenzyme deficiencies in the hyperbilirubinemic rat (Gunn rat). 56
1748678 1991
Sources

Variations for Crigler-Najjar Syndrome, Type I

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ClinVar genetic disease variations for Crigler-Najjar Syndrome, Type I:

6 (show top 50) (show all 64) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 UGT1A1 NM_001072.4(UGT1A6):c.862-6525C>ASNV Pathogenic 437210 rs72551340 2:234669155-234669155 2:233760509-233760509
2 UGT1A1 NM_000463.3(UGT1A1):c.622_625dup (p.Arg209fs)duplication Pathogenic 437209 rs766536479 2:234669555-234669558 2:233760908-233760909
3 UGT1A1 NM_001072.4(UGT1A6):c.874_887delinsA (p.Tyr292fs)indel Pathogenic 12266 rs587776761 2:234675692-234675705 2:233767046-233767059
4 UGT1A1 NM_001072.4(UGT1A6):c.1121C>T (p.Ser374Phe)SNV Pathogenic 12267 rs72551353 2:234676905-234676905 2:233768259-233768259
5 UGT1A1 NM_000463.3(UGT1A1):c.991C>T (p.Gln331Ter)SNV Pathogenic 12268 rs111033539 2:234675806-234675806 2:233767160-233767160
6 UGT1A1 NM_000463.3(UGT1A1):c.1021C>T (p.Arg341Ter)SNV Pathogenic 12269 rs72551349 2:234676519-234676519 2:233767873-233767873
7 UGT1A1 NM_001072.4(UGT1A6):c.862-6234_862-6232delshort repeat Pathogenic 12271 rs587776762 2:234669441-234669443 2:233760795-233760797
8 UGT1A1 NM_001072.4(UGT1A6):c.920G>A (p.Gly307Glu)SNV Pathogenic 12272 rs62625011 2:234675738-234675738 2:233767092-233767092
9 UGT1A1 NM_001072.4(UGT1A6):c.862-5907C>ASNV Pathogenic 12273 rs281865418 2:234669773-234669773 2:233761127-233761127
10 UGT1A1 NM_001072.4(UGT1A6):c.862-6273_862-6272insTinsertion Pathogenic 12276 rs587776763 2:234669407-234669408 2:233760761-233760762
11 UGT1A1 NM_001072.4(UGT1A6):c.862-5882G>CSNV Pathogenic 12277 rs587776764 2:234669798-234669798 2:233761152-233761152
12 UGT1A1 NM_001072.4(UGT1A6):c.862-6602C>TSNV Pathogenic 12278 rs587776765 2:234669078-234669078 2:233760432-233760432
13 UGT1A1 NM_001072.4(UGT1A6):c.1082-2A>GSNV Pathogenic 12279 rs587776766 2:234676864-234676864 2:233768218-233768218
14 UGT1A1 NM_001072.4(UGT1A6):c.1003C>T (p.Arg335Trp)SNV Pathogenic 437450 rs139607673 2:234676504-234676504 2:233767858-233767858
15 UGT1A1 NM_000463.3(UGT1A1):c.1070A>G (p.Gln357Arg)SNV Pathogenic 12283 rs72551351 2:234676568-234676568 2:233767922-233767922
16 UGT1A1 NM_001072.4(UGT1A6):c.862-6394dupduplication Pathogenic 266037 rs748219743 2:234669280-234669281 2:233760634-233760635
17 UGT1A1 NM_001072.4(UGT1A6):c.1453T>G (p.Tyr485Asp)SNV Pathogenic/Likely pathogenic 12281 rs34993780 2:234681059-234681059 2:233772413-233772413
18 UGT1A1 NM_001072.4(UGT1A6):c.862-6122C>TSNV Pathogenic/Likely pathogenic 437211 rs72551343 2:234669558-234669558 2:233760912-233760912
19 UGT1A1 NM_001072.4(UGT1A6):c.862-6138_862-6115deldeletion Likely pathogenic 437208 rs1553620849 2:234669541-234669564 2:233760895-233760918
20 UGT1A1 NM_001072.4(UGT1A6):c.862-6558C>TSNV Conflicting interpretations of pathogenicity 500144 rs191471887 2:234669122-234669122 2:233760476-233760476
21 UGT1A1 NM_000463.3(UGT1A1):c.964A>G (p.Ile322Val)SNV Conflicting interpretations of pathogenicity 724578 2:234675779-234675779 2:233767133-233767133
22 UGT1A1 NM_001072.4(UGT1A6):c.862-6606C>TSNV Conflicting interpretations of pathogenicity 160234 rs34526305 2:234669074-234669074 2:233760428-233760428
23 UGT1A1 NM_001072.4(UGT1A6):c.862-6073T>GSNV Conflicting interpretations of pathogenicity, other 160239 rs35003977 2:234669607-234669607 2:233760961-233760961
24 UGT1A1 NM_000463.3(UGT1A1):c.*419T>CSNV Conflicting interpretations of pathogenicity 898686 2:234681624-234681624 2:233772978-233772978
25 UGT1A1 NM_001072.4(UGT1A6):c.993+15T>CSNV Conflicting interpretations of pathogenicity 160241 rs4148327 2:234675826-234675826 2:233767180-233767180
26 UGT1A1 NM_001072.4(UGT1A6):c.1425C>T (p.Pro475=)SNV Conflicting interpretations of pathogenicity 160235 rs28900406 2:234681031-234681031 2:233772385-233772385
27 UGT1A1 NM_001072.4(UGT1A6):c.1119T>C (p.Gly373=)SNV Conflicting interpretations of pathogenicity 197147 rs139698110 2:234676903-234676903 2:233768257-233768257
28 UGT1A , UGT1A1 , UGT1A10 , UGT1A3 , UGT1A4 , UGT1A5 , UGT1A6 , UGT1A7 , UGT1A8 , UGT1A9 NM_001072.4(UGT1A6):c.1088C>T (p.Pro363Leu)SNV Conflicting interpretations of pathogenicity, other 212543 rs34946978 2:234676872-234676872 2:233768226-233768226
29 UGT1A1 NM_001072.4(UGT1A6):c.862-6207A>GSNV Conflicting interpretations of pathogenicity 289602 rs148755655 2:234669473-234669473 2:233760827-233760827
30 UGT1A1 NM_001072.4(UGT1A6):c.862-6421T>CSNV Conflicting interpretations of pathogenicity 289882 rs144217005 2:234669259-234669259 2:233760613-233760613
31 UGT1A1 NM_001072.4(UGT1A6):c.862-6170G>ASNV Uncertain significance 290430 rs375974892 2:234669510-234669510 2:233760864-233760864
32 UGT1A , UGT1A1 , UGT1A10 , UGT1A3 , UGT1A4 , UGT1A5 , UGT1A6 , UGT1A7 , UGT1A8 , UGT1A9 NM_001072.4(UGT1A6):c.1321C>T (p.Arg441Cys)SNV Uncertain significance 286999 rs143033456 2:234680927-234680927 2:233772281-233772281
33 UGT1A1 NM_001072.4(UGT1A6):c.*201G>ASNV Uncertain significance 335083 rs541532523 2:234681406-234681406 2:233772760-233772760
34 UGT1A1 NM_001072.4(UGT1A6):c.*585G>TSNV Uncertain significance 335087 rs886055800 2:234681790-234681790 2:233773144-233773144
35 UGT1A1 NM_001072.4(UGT1A6):c.862-6453T>CSNV Uncertain significance 335079 rs138183896 2:234669227-234669227 2:233760581-233760581
36 UGT1A1 NM_001072.4(UGT1A6):c.862-6447T>CSNV Uncertain significance 335080 rs374655757 2:234669233-234669233 2:233760587-233760587
37 UGT1A1 NM_001072.4(UGT1A6):c.862-6270C>TSNV Uncertain significance 335081 rs199766420 2:234669410-234669410 2:233760764-233760764
38 UGT1A1 NM_001072.4(UGT1A6):c.1319T>C (p.Met440Thr)SNV Uncertain significance 335082 rs202172337 2:234680925-234680925 2:233772279-233772279
39 UGT1A1 NM_000463.3(UGT1A1):c.*461G>TSNV Uncertain significance 895706 2:234681666-234681666 2:233773020-233773020
40 UGT1A1 NM_000463.3(UGT1A1):c.*674G>ASNV Uncertain significance 895991 2:234681879-234681879 2:233773233-233773233
41 UGT1A1 NM_001072.4(UGT1A6):c.1204C>T (p.Arg402Cys)SNV Uncertain significance 498359 rs778766461 2:234676988-234676988 2:233768342-233768342
42 UGT1A1 NM_001072.4(UGT1A6):c.862-5999T>CSNV Uncertain significance 160240 rs57307513 2:234669681-234669681 2:233761035-233761035
43 UGT1A1 NM_000463.3(UGT1A1):c.25C>T (p.Arg9Cys)SNV Uncertain significance 895439 2:234668958-234668958 2:233760312-233760312
44 UGT1A1 NM_000463.3(UGT1A1):c.288G>A (p.Gly96=)SNV Uncertain significance 897334 2:234669221-234669221 2:233760575-233760575
45 UGT1A1 NM_000463.3(UGT1A1):c.361G>C (p.Ala121Pro)SNV Uncertain significance 895502 2:234669294-234669294 2:233760648-233760648
46 UGT1A1 NM_000463.3(UGT1A1):c.584G>A (p.Arg195Lys)SNV Uncertain significance 897407 2:234669517-234669517 2:233760871-233760871
47 UGT1A1 NM_000463.3(UGT1A1):c.1180T>C (p.Phe394Leu)SNV Uncertain significance 895576 2:234676961-234676961 2:233768315-233768315
48 UGT1A1 NM_000463.3(UGT1A1):c.1410C>T (p.Gly470=)SNV Uncertain significance 896983 2:234681013-234681013 2:233772367-233772367
49 UGT1A1 NM_000463.3(UGT1A1):c.1411G>A (p.Ala471Thr)SNV Uncertain significance 897467 2:234681014-234681014 2:233772368-233772368
50 UGT1A1 NM_000463.3(UGT1A1):c.1518C>A (p.Thr506=)SNV Uncertain significance 897468 2:234681121-234681121 2:233772475-233772475

UniProtKB/Swiss-Prot genetic disease variations for Crigler-Najjar Syndrome, Type I:

73 (show all 21)
# Symbol AA change Variation ID SNP ID
1 UGT1A1 p.Cys177Arg VAR_007697 rs72551342
2 UGT1A1 p.Gly276Arg VAR_007699 rs72551345
3 UGT1A1 p.Ala292Val VAR_007700 rs758873309
4 UGT1A1 p.Gly308Glu VAR_007701 rs62625011
5 UGT1A1 p.Gln357Arg VAR_007703 rs72551351
6 UGT1A1 p.Ala368Thr VAR_007704 rs72551352
7 UGT1A1 p.Ser375Phe VAR_007705 rs72551353
8 UGT1A1 p.Ser381Arg VAR_007706 rs72551354
9 UGT1A1 p.Ala401Pro VAR_007707 rs72551355
10 UGT1A1 p.Lys428Glu VAR_007708 rs72551356
11 UGT1A1 p.His39Asp VAR_026135 rs72551339
12 UGT1A1 p.Glu291Val VAR_026138
13 UGT1A1 p.Arg336Leu VAR_026140
14 UGT1A1 p.Arg336Gln VAR_026141 rs750453538
15 UGT1A1 p.His376Arg VAR_026144 rs134903776
16 UGT1A1 p.Gly377Val VAR_026145 rs128365272
17 UGT1A1 p.Pro387Ser VAR_026146 rs901936528
18 UGT1A1 p.Gly395Val VAR_026147 rs367897068
19 UGT1A1 p.Trp461Arg VAR_026149 rs147650032
20 UGT1A1 p.Lys402Thr VAR_064960
21 UGT1A1 p.Asp36Asn VAR_071402

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Expression for Crigler-Najjar Syndrome, Type I

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Search GEO for disease gene expression data for Crigler-Najjar Syndrome, Type I.
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Pathways for Crigler-Najjar Syndrome, Type I

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Pathways related to Crigler-Najjar Syndrome, Type I according to KEGG:

36
# Name Kegg Source Accession
1 Porphyrin and chlorophyll metabolism hsa00860

Pathways related to Crigler-Najjar Syndrome, Type I according to GeneCards Suite gene sharing:

(show all 21)
# Super pathways Score Top Affiliating Genes
1
Metabolism 65
Show member pathways
 14.03 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
2
Cytochrome P450 - arranged by substrate type 65
Show member pathways
 13.2 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
3
Drug metabolism - cytochrome P450 36
Show member pathways
 12.84 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
4
Glucose / Energy Metabolism 4
12.55 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
5
Porphyrin and chlorophyll metabolism 36
Show member pathways
 12.26 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
6
NRF2 pathway 1
12.15 UGT1A9 UGT1A7 UGT1A6 UGT1A4 UGT1A3 UGT1A1
7
Statin Pathway - Generalized, Pharmacokinetics 60
Show member pathways
 11.83 UGT1A9 UGT1A3 UGT1A1
8
Carvedilol Pathway, Pharmacokinetics 60
Show member pathways
 11.8 UGT1A9 UGT1A8 UGT1A3 UGT1A10 UGT1A1
9
Acetaminophen Pathway (therapeutic doses), Pharmacokinetics 60
Show member pathways
 11.76 UGT1A9 UGT1A8 UGT1A6 UGT1A4 UGT1A3 UGT1A10
10
Phenytoin Pathway, Pharmacokinetics 60
Show member pathways
 11.67 UGT1A9 UGT1A6 UGT1A4 UGT1A1
11
Aryl Hydrocarbon Receptor Pathway 1
11.59 UGT1A9 UGT1A7 UGT1A6 UGT1A4 UGT1A3 UGT1A1
12
Irinotecan Pathway, Pharmacokinetics 60
Show member pathways
 11.53 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A4 UGT1A3
13
Tamoxifen metabolism 1
Show member pathways
 11.44 UGT1A8 UGT1A4 UGT1A3 UGT1A10
14
Steroid hormone biosynthesis 36
Show member pathways
 11.44 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
15
Constitutive Androstane Receptor Pathway 1
11.38 UGT1A9 UGT1A6 UGT1A4 UGT1A3 UGT1A1
16
Estrogen metabolism 1
Show member pathways
 11.38 UGT1A9 UGT1A8 UGT1A6 UGT1A4 UGT1A3 UGT1A1
17
Erlotinib Pathway, Pharmacokinetics 60
Show member pathways
 11.3 UGT1A9 UGT1A7 UGT1A1
18
Bile secretion 36
11.23 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
19
Bupropion Pathway, Pharmacokinetics 60
10.89 UGT1A9 UGT1A4 UGT1A3
20
Lamotrigine Pathway, Pharmacokinetics and Pharmacodynamics 60
10.77 UGT1A4 UGT1A3
21
Propranolol Pathway, Pharmacokinetics 60
10.54 UGT1A9 UGT1A10
Sources

GO Terms for Crigler-Najjar Syndrome, Type I

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Cellular components related to Crigler-Najjar Syndrome, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.85 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
2 endoplasmic reticulum membrane GO:0005789 9.61 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
3 intracellular membrane-bounded organelle GO:0043231 9.32 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4

Biological processes related to Crigler-Najjar Syndrome, Type I according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 retinoic acid metabolic process GO:0042573 9.72 UGT1A9 UGT1A8 UGT1A7 UGT1A3 UGT1A1
2 cellular glucuronidation GO:0052695 9.7 UGT1A9 UGT1A7 UGT1A6 UGT1A4 UGT1A3 UGT1A10
3 flavone metabolic process GO:0051552 9.65 UGT1A9 UGT1A8 UGT1A7 UGT1A10 UGT1A1
4 negative regulation of catalytic activity GO:0043086 9.63 UGT1A8 UGT1A7 UGT1A1
5 xenobiotic glucuronidation GO:0052697 9.61 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
6 nucleotide metabolic process GO:0009117 9.54 NT5C2 NT5C1A
7 drug metabolic process GO:0017144 9.54 UGT1A7 UGT1A1 NT5C2
8 purine nucleotide catabolic process GO:0006195 9.52 NT5C2 NT5C1A
9 adenosine metabolic process GO:0046085 9.51 NT5C2 NT5C1A
10 heme catabolic process GO:0042167 9.49 UGT1A4 UGT1A1
11 coumarin metabolic process GO:0009804 9.48 UGT1A8 UGT1A7
12 negative regulation of steroid metabolic process GO:0045939 9.43 UGT1A8 UGT1A1
13 bilirubin conjugation GO:0006789 9.4 UGT1A4 UGT1A1
14 flavonoid glucuronidation GO:0052696 9.28 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4

Molecular functions related to Crigler-Najjar Syndrome, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 10.1 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
2 protein homodimerization activity GO:0042803 9.97 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A4 UGT1A3
3 enzyme binding GO:0019899 9.92 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A4 UGT1A3
4 transferase activity, transferring glycosyl groups GO:0016757 9.91 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
5 retinoic acid binding GO:0001972 9.76 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A4 UGT1A3
6 enzyme inhibitor activity GO:0004857 9.61 UGT1A8 UGT1A7 UGT1A1
7 transferase activity, transferring hexosyl groups GO:0016758 9.61 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
8 steroid binding GO:0005496 9.48 UGT1A8 UGT1A1
9 5'-nucleotidase activity GO:0008253 9.46 NT5C2 NT5C1A
10 glucuronosyltransferase activity GO:0015020 9.28 UGT1A9 UGT1A8 UGT1A7 UGT1A6 UGT1A5 UGT1A4
Sources

Sources for Crigler-Najjar Syndrome, Type I

About this section
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
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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