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TYRSN1
MCID: TYR012
MIFTS: 66

Tyrosinemia, Type I (TYRSN1)

Categories: Blood diseases, Cancer diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Skin diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Tyrosinemia, Type I

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MalaCards integrated aliases for Tyrosinemia, Type I:

Name: Tyrosinemia, Type I 56 13 37 71
Tyrosinemia Type I 12 24 52 58 73 29 54 6 15 39
Hepatorenal Tyrosinemia 56 12 74 24 52 58 73
Fumarylacetoacetase Deficiency 56 24 52 58 73
Fah Deficiency 56 24 52 58 73
Fumarylacetoacetate Hydrolase Deficiency 24 58
Tyrosinemia Type 1 52 58
Tyrsn1 56 73
Tyrosinemia 1 73

Characteristics:

Orphanet epidemiological data:

58
tyrosinemia type 1
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Worldwide),1-9/100000,1-5/10000; Age of onset: All ages; Age of death: any age;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
high incidence in saguenay-lac st. jean region of the province of quebec, canada and northern europe
unusual cabbage-like odor
symptoms highly variable - rapidly progressive course leading to hepatic failure versus acute hepatic crisis


HPO:

31
tyrosinemia, type i:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases Cancer diseases
Anatomical: Neuronal diseases Liver diseases Nephrological diseases Eye diseases Skin diseases Gastrointestinal diseases Blood diseases Mental diseases
See all MalaCards categories (disease lists)
ICD10: 33
Orphanet: 58  
Rare neurological diseases
Rare hepatic diseases
Rare renal diseases
Inborn errors of metabolism


Sources

Summaries for Tyrosinemia, Type I

About this section
NIH Rare Diseases : 52 Tyrosinemia type 1 is a genetic disorder characterized by elevated blood levels of the amino acid tyrosine, a building block of most proteins . This condition is caused by a shortage of the enzyme fumarylacetoacetate hydrolase, one of the enzymes required for the multi-step process that breaks down tyrosine. This enzyme shortage is caused by mutations in the FAH gene . Symptoms usually appear in the first few months of life and include failure to thrive , diarrhea, vomiting, jaundice , cabbage-like odor, and increased tendency to bleed (particularly nosebleeds). Tyrosinemia type I can lead to liver and kidney failure, softening and weakening of the bones, problems affecting the nervous system, and an increased risk of liver cancer . This condition is inherited in an autosomal recessive manner. Treatment should be started as soon as the condition is diagnosed and includes a diet restricted in tyrosine and phenylalanine along with nitisinone, a medication that blocks the second step in the tyrosine degradation pathway.

MalaCards based summary : Tyrosinemia, Type I, also known as tyrosinemia type i, is related to glycine n-methyltransferase deficiency and tyrosinemia. An important gene associated with Tyrosinemia, Type I is FAH (Fumarylacetoacetate Hydrolase), and among its related pathways/superpathways are Metabolism and Viral mRNA Translation. The drugs Nitisinone and Tyrosine have been mentioned in the context of this disorder. Affiliated tissues include Liver, kidney and bone, and related phenotypes are generalized aminoaciduria and splenomegaly

Disease Ontology : 12 A tyrosinemia that has material basis in deficiency of the enzyme fumarylacetoacetate hydrolase resulting in an increase in fumarylacetoacetate which inhibits previous steps in tyrosine degradation leading to an accumulation of tyrosine in the body.

OMIM : 56 Hereditary tyrosinemia type I is an autosomal recessive disorder caused by deficiency of fumarylacetoacetase (FAH), the last enzyme of tyrosine degradation. The disorder is characterized by progressive liver disease and a secondary renal tubular dysfunction leading to hypophosphatemic rickets. Onset varies from infancy to adolescence. In the most acute form patients present with severe liver failure within weeks after birth, whereas rickets may be the major symptom in chronic tyrosinemia. Untreated, patients die from cirrhosis or hepatocellular carcinoma at a young age (summary by Bliksrud et al., 2005). (276700)

UniProtKB/Swiss-Prot : 73 Tyrosinemia 1: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and hepatorenal manifestations. Typical features include hepatic necrosis, renal tubular injury, episodic weakness, self-mutilation, and seizures. Renal tubular dysfunction is associated with phosphate loss and hypophosphataemic rickets. Progressive liver disease can lead to the development of hepatocellular carcinoma. Dietary treatment with restriction of tyrosine and phenylalanine alleviates the rickets, but liver transplantation has so far been the only definite treatment.

Wikipedia : 74 Tyrosinemia type I is a genetic disorder that disrupts the metabolism of the amino acid tyrosine,... more...

GeneReviews: NBK1515
Sources

Related Diseases for Tyrosinemia, Type I

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Diseases in the Tyrosinemia family:

Tyrosinemia, Type Ii Tyrosinemia, Type I
Tyrosinemia, Type Iii

Diseases related to Tyrosinemia, Type I via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 114)
# Related Disease Score Top Affiliating Genes
1 glycine n-methyltransferase deficiency 31.9 GNMT AHCY
2 tyrosinemia 30.8 TYR TAT SERPINA1 OTC HPD HGD
3 abdominal obesity-metabolic syndrome 1 30.1 OTC HGD FAH
4 hypermethioninemia 30.1 GNMT FAH AHCY
5 liver disease 30.0 SERPINA1 FAH CYCS AFP
6 inherited metabolic disorder 29.7 SERPINA1 PCSK9 NAGS
7 alkaptonuria 29.3 TYR TAT HPD HGD GSTZ1 FAH
8 maleylacetoacetate isomerase deficiency 11.5
9 tyrosinosis 11.3
10 bile acid synthesis defect, congenital, 1 11.3
11 folate malabsorption, hereditary 11.3
12 bile acid synthesis defect, congenital, 2 11.3
13 pediatric hepatocellular carcinoma 11.3
14 autosomal recessive disease 10.5
15 rickets 10.5
16 hepatocellular carcinoma 10.4
17 fanconi renotubular syndrome 2 10.3
18 fanconi syndrome 10.3
19 prostate calculus 10.3 HPD HGD
20 polyembryoma 10.3 SERPINA1 AFP
21 porphyria 10.3
22 liver cirrhosis 10.3
23 tyrosinemia, type ii 10.3 TAT HPD FAH
24 tyrosinemia, type iii 10.3 TAT HPD FAH
25 lower urinary tract calculus 10.3 HPD HGD
26 hawkinsinuria 10.2 TAT HPD FAH
27 ovarian mixed germ cell neoplasm 10.2 SERPINA1 AFP
28 liver sarcoma 10.2 SERPINA1 AFP
29 phenylketonuria 10.2
30 acute liver failure 10.2
31 renal osteodystrophy 10.1
32 hemifacial microsomia 10.1
33 hypophosphatemia 10.1
34 hepatoblastoma 10.1
35 craniofacial microsomia 10.1
36 fanconi renotubular syndrome 1 10.1
37 galactosemia i 10.1
38 hypophosphatemic rickets, x-linked recessive 10.1
39 renal tubular acidosis 10.1
40 pancreatoblastoma 10.1 SERPINA1 AFP
41 chromosome xp21 deletion syndrome 10.1 OTC DMD
42 ochronosis 10.1 TYR HPD HGD
43 alpha-1-antitrypsin deficiency 10.1 SERPINA1 OTC AFP
44 angelman syndrome 10.0
45 atrial standstill 1 10.0
46 attention deficit-hyperactivity disorder 10.0
47 hereditary leiomyomatosis and renal cell cancer 10.0
48 fructose-1,6-bisphosphatase deficiency 10.0
49 alacrima, achalasia, and mental retardation syndrome 10.0
50 lennox-gastaut syndrome 10.0

Graphical network of the top 20 diseases related to Tyrosinemia, Type I:



Diseases related to Tyrosinemia, Type I
Sources

Symptoms & Phenotypes for Tyrosinemia, Type I

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Human phenotypes related to Tyrosinemia, Type I:

58 31 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 generalized aminoaciduria 58 31 hallmark (90%) Very frequent (99-80%) HP:0002909
2 splenomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001744
3 hepatomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002240
4 acute hepatic failure 58 31 occasional (7.5%) Occasional (29-5%) HP:0006554
5 hepatocellular carcinoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0001402
6 rickets of the lower limbs 58 31 occasional (7.5%) Occasional (29-5%) HP:0006463
7 failure to thrive 31 HP:0001508
8 renal insufficiency 31 HP:0000083
9 hypertrophic cardiomyopathy 31 HP:0001639
10 hypoglycemia 31 HP:0001943
11 ascites 31 HP:0001541
12 cirrhosis 31 HP:0001394
13 gastrointestinal hemorrhage 31 HP:0002239
14 elevated hepatic transaminase 31 HP:0002910
15 nephrocalcinosis 31 HP:0000121
16 abnormal bleeding 31 HP:0001892
17 abnormality of coagulation 31 HP:0001928
18 elevated alpha-fetoprotein 31 HP:0006254
19 enlarged kidney 31 HP:0000105
20 pancreatic islet-cell hyperplasia 31 HP:0004510
21 periodic paralysis 31 HP:0003768
22 renal fanconi syndrome 31 HP:0001994
23 abnormality of the abdominal wall 31 HP:0004298
24 elevated urinary delta-aminolevulinic acid 31 HP:0003163
25 glomerulosclerosis 31 HP:0000096
26 hypophosphatemic rickets 31 HP:0004912
27 hypermethioninemia 31 HP:0003235
28 paralytic ileus 31 HP:0002590
29 hypertyrosinemia 31 HP:0003231
30 episodic peripheral neuropathy 31 HP:0006949

Symptoms via clinical synopsis from OMIM:

56
Abdomen Spleen:
splenomegaly

Growth Other:
failure to thrive

Skeletal:
rickets

Abdomen External Features:
ascites

Neoplasia:
hepatocellular carcinoma

Abdomen Gastrointestinal:
paralytic ileus
gi bleeding

Muscle Soft Tissue:
chronic weakness

Neurologic Central Nervous System:
episodic paralysis

Abdomen Liver:
hepatomegaly
cirrhosis
acute liver failure

Laboratory Abnormalities:
hypophosphatemia
hypoglycemia
elevated alpha-fetoprotein
elevated urinary delta-aminolevulinic acid
tyrosinemia
more
Cardiovascular Heart:
hypertrophic cardiomyopathy

Genitourinary Kidneys:
nephrocalcinosis
renal fanconi syndrome
glomerulosclerosis
renal failure
nephromegaly

Metabolic Features:
renal fanconi syndrome
hypophosphatemic rickets

Neurologic Peripheral Nervous System:
episodic peripheral neuropathy

Abdomen Pancreas:
pancreatic islet-cell hypertrophy

Hematology:
abnormal blood coagulation studies (prolonged pt and ptt)

Clinical features from OMIM:

276700

GenomeRNAi Phenotypes related to Tyrosinemia, Type I according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.55 DGUOK
2 Decreased viability GR00221-A-2 9.55 DGUOK
3 Decreased viability GR00249-S 9.55 AFP FAH TYR
4 Decreased viability GR00342-S-2 9.55 DGUOK
5 Decreased viability GR00342-S-3 9.55 DGUOK
6 Decreased viability GR00381-A-1 9.55 HGD
7 Decreased viability GR00386-A-1 9.55 AHCY ALAD GNMT HPD
8 Decreased viability GR00402-S-2 9.55 AFP AHCY ALAD CYCS DMD
9 Decreased shRNA abundance GR00297-A 9.26 AHCY CYCS DGUOK TAT

MGI Mouse Phenotypes related to Tyrosinemia, Type I:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.07 AFP ALAD ASL DMD FAH GNMT
2 behavior/neurological MP:0005386 10.02 AFP ALAD ASL CYCS DGUOK DMD
3 mortality/aging MP:0010768 9.77 AFP AHCY ALAD ASL CYCS DMD
4 liver/biliary system MP:0005370 9.76 AFP DMD FAH GNMT GSTZ1 HGD
5 renal/urinary system MP:0005367 9.23 ASL DMD FAH GSTZ1 HGD HPD
Sources

Drugs & Therapeutics for Tyrosinemia, Type I

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Drugs for Tyrosinemia, Type I (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Nitisinone Approved, Investigational Phase 2 104206-65-7 115355
2
Tyrosine Approved, Investigational, Nutraceutical Phase 2 60-18-4 6057

Interventional clinical trials:

(show all 12)
# Name Status NCT ID Phase Drugs
1 Open-label, Multicentre, Multiple-dose Trial to Evaluate Pharmacokinetics, Efficacy and Safety of Once Daily Dosing Compared to Twice Daily Dosing of Orfadin in Patients Diagnosed With Hereditary Tyrosinemia Type 1 Completed NCT02323529 Phase 3 Nitisinone
2 Phase II Study of the Enzyme Inhibitor NTBC for Tyrosinemia Type I Completed NCT00004333 Phase 2 NTBC
3 Long-Term Clinical Trial of Nitisinone in Alkaptonuria Completed NCT00107783 Phase 2 Nitisinone (NTBC)
4 Taste and Palatability of Orfadin Suspension. An Open, Non-controlled 3 Day Study in Pediatric Patients With Hereditary Tyrosinemia Type 1 Treated With Orfadin. Completed NCT01734889 Phase 1 Nitisinone
5 A Three-Period Crossover Study to Determine the Bioequivalence of Two Oral Formulations Containing Nitisinone 10 mg Compared to Reference Formulation Orfadin In Healthy Subjects Under Fasting Conditions Completed NCT02750345 Phase 1 Nitisinone;Nitisinone Baked Tablet;Orfadin
6 A Single Center, Single-Dose, Open-Label, Randomized Study to Compare the Bioavailability of an Oral Test Formulation Containing Nitisinone 10 mg in at Least 16 Healthy Male and Female Subjects Under Fasting and Fed Conditions Completed NCT02750332 Phase 1 Nitisinone
7 A Single Center, Single-Dose, Open-Label, Laboratory-Blind, Randomized, Three-Period Crossover Study to Determine the Bioequivalence of Two Oral Formulations Containing of Nitisinone 10 mg Compared to the Reference Formulation Orfadin 10 mg in at Least 18 Healthy Male and Female Subjects Under Fasting Conditions Completed NCT02750709 Phase 1 Nitisinone;Nitisinone 10 mg Tablet High Compritol;Orfadin
8 A Non-interventional Post Authorization Study (PASS) to Evaluate Long-term Safety of Orfadin Treatment in Hypertyrosinemia Type 1 (HT-1) Patients in Standard Care Completed NCT02320084 Nitisinone
9 Prevention of Dichloroacetate Toxicity Completed NCT00031161 Nitisinone (NTBC);Dichloroacetate
10 Hereditary Hepatorenal Tyrosinemia Natural History (Multicenter Clinical Study): Registry for Patients With Tyrosinemia Type I in Egypt and the Arab World Recruiting NCT03446586
11 BioTyrosin - Biomarker for the Early Diagnosis and Monitoring in Tyrosinemia Type 1 - An International, Multicenter, Epidemiological Protocol Active, not recruiting NCT03284658
12 Orfadin and Nitinosine Study Not yet recruiting NCT04113772 Nitisinone;Orfadin

Search NIH Clinical Center for Tyrosinemia, Type I

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Read about Tyrosinemia, Type I cell therapies at LifeMap Discovery.
Stem-cell-based therapeutic approaches for Tyrosinemia, Type I:
Fibroblast-reprogrammed hepatocytes to treat hereditary tyrosinemia type I
Hepatocyte transplantation for treatment of liver disorders
Embryonic/Adult Cultured Cells Related to Tyrosinemia, Type I:
Induced hepatocyte-like cells PMIDs: 21716291
Hepatocytes PMIDs: 12777539 22167636 22789058 9580649 15239608
Sources

Genetic Tests for Tyrosinemia, Type I

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Genetic tests related to Tyrosinemia, Type I:

# Genetic test Affiliating Genes
1 Tyrosinemia Type I 29 FAH
Sources

Anatomical Context for Tyrosinemia, Type I

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MalaCards organs/tissues related to Tyrosinemia, Type I:

40
Liver, Kidney, Bone, Pancreatic Islet, Testes, Bone Marrow, Lymph Node
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

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

Publications for Tyrosinemia, Type I

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Articles related to Tyrosinemia, Type I:

(show top 50) (show all 317)
# Title Authors PMID Year
1
Different clinical forms of hereditary tyrosinemia (type I) in patients with identical genotypes. 54 24 6 61
9705236 1998
2
Self-induced correction of the genetic defect in tyrosinemia type I. 56 24 54 61
7929843 1994
3
A single mutation of the fumarylacetoacetate hydrolase gene in French Canadians with hereditary tyrosinemia type I. 6 56 61
8028615 1994
4
Fumarylacetoacetase mutations in tyrosinaemia type I. 56 6
8829657 1996
5
Tyrosinaemia type I--de novo mutation in liver tissue suppressing an inborn splicing defect. 24 56
15759101 2005
6
Splicing mutations, mainly IVS6-1(G>T), account for 70% of fumarylacetoacetate hydrolase (FAH) gene alterations, including 7 novel mutations, in a survey of 29 tyrosinemia type I patients. 61 54 56
12203990 2002
7
Hepatocellular carcinoma despite long-term survival in chronic tyrosinaemia I. 24 6
11196105 2000
8
Deficient DNA-ligase activity in the metabolic disease tyrosinemia type I. 54 61 56
9770534 1998
9
Adenovirus-mediated gene therapy in a mouse model of hereditary tyrosinemia type I. 54 61 56
9095403 1997
10
Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: overview. 61 54 56
9101289 1997
11
Identification of a stop mutation in five Finnish patients suffering from hereditary tyrosinemia type I. 6 61 54
8162054 1994
12
Hereditary tyrosinemia type I. Self-induced correction of the fumarylacetoacetase defect. 61 54 56
8473520 1993
13
Mutations of the fumarylacetoacetate hydrolase gene in four patients with tyrosinemia, type I. 6 61 54
8318997 1993
14
Different molecular basis for fumarylacetoacetate hydrolase deficiency in the two clinical forms of hereditary tyrosinemia (type I). 61 54 56
2378356 1990
15
Fumarylacetoacetase measurement as a mass-screening procedure for hereditary tyrosinemia type I. 56 61 54
2378358 1990
16
Neurologic crises in hereditary tyrosinemia. 24 56
2153931 1990
17
A novel mutation causing mild, atypical fumarylacetoacetase deficiency (Tyrosinemia type I): a case report. 61 54 24
20003495 2009
18
Tyrosinemia Type I 61 6
20301688 2006
19
No evidence of maternal cell colonization in reverted liver nodules of tyrosinemia type I patients. 54 61 24
15521007 2004
20
Frequent mutation reversion inversely correlates with clinical severity in a genetic liver disease, hereditary tyrosinemia. 24 61 54
14691918 2003
21
Mutation analysis of the FAH gene in Israeli patients with tyrosinemia type I. 61 54 24
11754109 2002
22
Spectrophotometric microassay for delta-aminolevulinate dehydratase in dried-blood spots as confirmation for hereditary tyrosinemia type I. 24 54 61
11468232 2001
23
Six novel mutations in the fumarylacetoacetate hydrolase gene of patients with hereditary tyrosinemia type I. 61 56
8723690 1996
24
The nephropathy of type I tyrosinemia after liver transplantation. 56 54
7603784 1995
25
Two novel mutations involved in hereditary tyrosinemia type I. 61 6
7757089 1995
26
Identification of a frequent pseudodeficiency mutation in the fumarylacetoacetase gene, with implications for diagnosis of tyrosinemia type I. 56 61
7977370 1994
27
Hereditary tyrosinemia type I: strong association with haplotype 6 in French Canadians permits simple carrier detection and prenatal diagnosis. 61 56
7913582 1994
28
Hereditary tyrosinemia type I: lack of correlation between clinical findings and amount of immunoreactive fumarylacetoacetase protein. 56 61
1594329 1992
29
Genetic epidemiology of hereditary tyrosinemia in Quebec and in Saguenay-Lac-St-Jean. 61 56
2378355 1990
30
Visceral pathology of hereditary tyrosinemia type I. 56 61
2378357 1990
31
Hereditary tyrosinemia type I (chronic form): pathologic findings in the liver. 56 61
2536631 1989
32
Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. 61 24
28771246 2017
33
Silent Tyrosinemia Type I Without Elevated Tyrosine or Succinylacetone Associated with Liver Cirrhosis and Hepatocellular Carcinoma. 24 61
27397503 2016
34
Single dose NTBC-treatment of hereditary tyrosinemia type I. 24 61
22307209 2012
35
Maternal and fetal tyrosinemia type I. 24 61
23250512 2010
36
Hepatocellular carcinoma in hereditary tyrosinemia type I despite 2-(2 nitro-4-3 trifluoro- methylbenzoyl)-1, 3-cyclohexanedione treatment. 24 61
15625434 2005
37
Corneal opacities associated with NTBC treatment. 61 24
12140036 2002
38
Carnitine-deficient myopathy as a presentation of tyrosinemia type I. 61 24
11575602 2001
39
Point mutations in the murine fumarylacetoacetate hydrolase gene: Animal models for the human genetic disorder hereditary tyrosinemia type 1. 56
11209059 2001
40
Hepatocyte injury in tyrosinemia type 1 is induced by fumarylacetoacetate and is inhibited by caspase inhibitors. 56
9689118 1998
41
Tyrosinaemia type I and NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione). 56
9728331 1998
42
Complete rescue of lethal albino c14CoS mice by null mutation of 4-hydroxyphenylpyruvate dioxygenase and induction of apoptosis of hepatocytes in these mice by in vivo retrieval of the tyrosine catabolic pathway. 56
9305902 1997
43
Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinaemia type I. 56
8589717 1996
44
Round two for liver gene therapy. 56
8589710 1996
45
Simple detection of a (Finnish) hereditary tyrosinemia type 1 mutation. 6
8723698 1996
46
Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type I. 56
7545495 1995
47
Heterozygosity for an exon 12 splicing mutation and a W234G missense mutation in an American child with chronic tyrosinemia type 1. 56
7550234 1995
48
Hereditary tyrosinemia type I: a new clinical classification with difference in prognosis on dietary treatment. 61 24
7927251 1994
49
Characterization of the human fumarylacetoacetate hydrolase gene and identification of a missense mutation abolishing enzymatic activity. 6
8364576 1993
50
Liver transplantation for hereditary tyrosinemia--early transplantation following the patient's stabilization. 56
1440864 1992
Sources

Variations for Tyrosinemia, Type I

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ClinVar genetic disease variations for Tyrosinemia, Type I:

6 (show top 50) (show all 166) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FAH NM_000137.3(FAH):c.1021C>T (p.Arg341Trp)SNV Benign/Likely benign, other 11868 rs11555096 15:80472526-80472526 15:80180184-80180184
2 FAH NM_000137.4(FAH):c.1062+5G>ASNV Pathogenic 11870 rs80338901 15:80472572-80472572 15:80180230-80180230
3 FAH NM_000137.3(FAH):c.1069G>T (p.Glu357Ter)SNV Pathogenic 11871 rs121965075 15:80473390-80473390 15:80181048-80181048
4 FAH NM_000137.3(FAH):c.786G>A (p.Trp262Ter)SNV Pathogenic 11873 rs80338899 15:80465435-80465435 15:80173093-80173093
5 FAH NM_000137.3(FAH):c.554-1G>TSNV Pathogenic 11874 rs80338895 15:80460605-80460605 15:80168263-80168263
6 FAH NM_000137.3(FAH):c.836A>G (p.Gln279Arg)SNV Pathogenic 11875 rs121965078 15:80465485-80465485 15:80173143-80173143
7 FAH NM_000137.3(FAH):c.192G>T (p.Gln64His)SNV Pathogenic 21054 rs80338894 15:80450512-80450512 15:80158170-80158170
8 FAH NM_000137.3(FAH):c.47A>T (p.Asn16Ile)SNV Pathogenic 11865 rs121965073 15:80445443-80445443 15:80153101-80153101
9 FAH NM_000137.3(FAH):c.1090G>T (p.Glu364Ter)SNV Pathogenic 11867 rs121965076 15:80473411-80473411 15:80181069-80181069
10 FAH NM_000137.3(FAH):c.698A>T (p.Asp233Val)SNV Pathogenic 21057 rs80338897 15:80464582-80464582 15:80172240-80172240
11 FAH NM_000137.3(FAH):c.963C>A (p.Tyr321Ter)SNV Pathogenic 291075 rs886044640 15:80472468-80472468 15:80180126-80180126
12 FAH NM_000137.3(FAH):c.1A>G (p.Met1Val)SNV Pathogenic 372766 rs1057517972 15:80445397-80445397 15:80153055-80153055
13 FAH NM_000137.3(FAH):c.709C>T (p.Arg237Ter)SNV Pathogenic 437463 rs769550316 15:80465358-80465358 15:80173016-80173016
14 FAH NM_000137.3(FAH):c.1210G>A (p.Gly404Ser)SNV Pathogenic 459903 rs1297118863 15:80478501-80478501 15:80186159-80186159
15 FAH NM_000137.3(FAH):c.835del (p.Gln279fs)deletion Pathogenic 551130 rs1555441703 15:80465484-80465484 15:80173142-80173142
16 FAH NM_000137.3(FAH):c.1025C>T (p.Pro342Leu)SNV Pathogenic 551024 rs779040832 15:80472530-80472530 15:80180188-80180188
17 FAH NM_000137.3(FAH):c.707-1G>ASNV Pathogenic 558607 rs149052294 15:80465355-80465355 15:80173013-80173013
18 FAH NM_000137.4(FAH):c.978dup (p.Leu327fs)duplication Pathogenic 656983 15:80472482-80472483 15:80180140-80180141
19 FAH NM_000137.3(FAH):c.82_83del (p.Pro28fs)deletion Pathogenic 635516 15:80450402-80450403 15:80158060-80158061
20 FAH NM_000137.4(FAH):c.1003_1004del (p.Val335fs)deletion Pathogenic 803110 15:80472507-80472508 15:80180165-80180166
21 FAH NM_000137.4(FAH):c.982C>T (p.Gln328Ter)SNV Pathogenic 813492 15:80472487-80472487 15:80180145-80180145
22 FAH NM_000137.4(FAH):c.1180+1G>ASNV Pathogenic 813493 15:80473502-80473502 15:80181160-80181160
23 FAH NC_000015.10:g.(?_80177527)_(80186219_?)deldeletion Pathogenic 830521 15:80469869-80478561
24 FAH NM_000137.4(FAH):c.221del (p.Gly74fs)deletion Pathogenic 862144 15:80452124-80452124 15:80159782-80159782
25 FAH NM_000137.4(FAH):c.1063-1G>ASNV Pathogenic 848070 15:80473383-80473383 15:80181041-80181041
26 FAH NM_000137.3(FAH):c.1027G>T (p.Gly343Trp)SNV Pathogenic/Likely pathogenic 576751 rs970505762 15:80472532-80472532 15:80180190-80180190
27 FAH NM_000137.4(FAH):c.553+2_553+3delshort repeat Pathogenic/Likely pathogenic 552185 rs1555441272 15:80460491-80460492 15:80168149-80168150
28 FAH NM_000137.3(FAH):c.706+2T>GSNV Pathogenic/Likely pathogenic 550532 rs1555441597 15:80464592-80464592 15:80172250-80172250
29 FAH NM_000137.3(FAH):c.782C>T (p.Pro261Leu)SNV Pathogenic/Likely pathogenic 21058 rs80338898 15:80465431-80465431 15:80173089-80173089
30 FAH NM_000137.3(FAH):c.456G>A (p.Trp152Ter)SNV Pathogenic/Likely pathogenic 92445 rs370686447 15:80460394-80460394 15:80168052-80168052
31 FAH NM_000137.3(FAH):c.192+1G>TSNV Pathogenic/Likely pathogenic 189085 rs786204683 15:80450513-80450513 15:80158171-80158171
32 FAH NM_000137.3(FAH):c.520C>T (p.Arg174Ter)SNV Pathogenic/Likely pathogenic 188751 rs781496816 15:80460458-80460458 15:80168116-80168116
33 FAH NM_000137.3(FAH):c.1009G>A (p.Gly337Ser)SNV Pathogenic/Likely pathogenic 11869 rs80338900 15:80472514-80472514 15:80180172-80180172
34 FAH NM_000137.3(FAH):c.1141A>G (p.Arg381Gly)SNV Likely pathogenic 11872 rs121965077 15:80473462-80473462 15:80181120-80181120
35 FAH NM_000137.3(FAH):c.401C>A (p.Ala134Asp)SNV Likely pathogenic 11866 rs121965074 15:80454624-80454624 15:80162282-80162282
36 FAH NM_000137.4(FAH):c.726G>A (p.Trp242Ter)SNV Likely pathogenic 813490 15:80465375-80465375 15:80173033-80173033
37 FAH NM_000137.4(FAH):c.880A>C (p.Thr294Pro)SNV Likely pathogenic 813491 15:80467400-80467400 15:80175058-80175058
38 FAH NM_000137.4(FAH):c.745C>T (p.Pro249Ser)SNV Likely pathogenic 803109 15:80465394-80465394 15:80173052-80173052
39 FAH NM_000137.4(FAH):c.606+1G>ASNV Likely pathogenic 851025 15:80460659-80460659 15:80168317-80168317
40 FAH NM_000137.3(FAH):c.607-1G>ASNV Likely pathogenic 188755 rs771712041 15:80464490-80464490 15:80172148-80172148
41 FAH NM_000137.3(FAH):c.1190del (p.Gln397fs)deletion Likely pathogenic 188907 rs786204551 15:80478481-80478481 15:80186139-80186139
42 FAH NM_000137.3(FAH):c.2T>A (p.Met1Lys)SNV Likely pathogenic 371005 rs1057516934 15:80445398-80445398 15:80153056-80153056
43 FAH NM_000137.3(FAH):c.14del (p.Pro5fs)deletion Likely pathogenic 371526 rs1057517341 15:80445408-80445408 15:80153066-80153066
44 FAH NM_000137.3(FAH):c.81+2T>CSNV Likely pathogenic 370962 rs772895065 15:80445479-80445479 15:80153137-80153137
45 FAH NM_000137.3(FAH):c.314+1G>ASNV Likely pathogenic 370334 rs1057516408 15:80452220-80452220 15:80159878-80159878
46 FAH NM_000137.3(FAH):c.438del (p.Asn146fs)deletion Likely pathogenic 370316 rs779642226 15:80454661-80454661 15:80162319-80162319
47 FAH NM_000137.3(FAH):c.455G>A (p.Trp152Ter)SNV Likely pathogenic 370677 rs1057516679 15:80454678-80454678 15:80162336-80162336
48 FAH NM_000137.3(FAH):c.461_491del (p.His154fs)deletion Likely pathogenic 370684 rs1057516684 15:80460398-80460428 15:80168056-80168086
49 FAH NM_000137.3(FAH):c.492del (p.Ser165fs)deletion Likely pathogenic 371234 rs1057517113 15:80460429-80460429 15:80168087-80168087
50 FAH NM_000137.3(FAH):c.615del (p.Phe205fs)deletion Likely pathogenic 371201 rs1057517084 15:80464493-80464493 15:80172151-80172151

UniProtKB/Swiss-Prot genetic disease variations for Tyrosinemia, Type I:

73 (show all 20)
# Symbol AA change Variation ID SNP ID
1 FAH p.Asn16Ile VAR_005205 rs121965073
2 FAH p.Phe62Cys VAR_005206
3 FAH p.Gln64His VAR_005207 rs80338894
4 FAH p.Ala134Asp VAR_005208 rs121965074
5 FAH p.Gly158Asp VAR_005209
6 FAH p.Val166Gly VAR_005210 rs778387055
7 FAH p.Cys193Arg VAR_005211
8 FAH p.Gly207Asp VAR_005212 rs754196530
9 FAH p.Asp233Val VAR_005213 rs80338897
10 FAH p.Trp234Gly VAR_005214 rs155544159
11 FAH p.Pro249Thr VAR_005215
12 FAH p.Pro261Leu VAR_005216 rs80338898
13 FAH p.Thr294Pro VAR_005217 rs370634385
14 FAH p.Gly337Ser VAR_005218 rs80338900
15 FAH p.Pro342Leu VAR_005220 rs779040832
16 FAH p.Gly369Val VAR_005222
17 FAH p.Arg381Gly VAR_005223 rs121965077
18 FAH p.Phe405His VAR_005224
19 FAH p.Ala35Thr VAR_065454
20 FAH p.Gln279Arg VAR_065455 rs121965078

Cosmic variations for Tyrosinemia, Type I:

9 (show top 50) (show all 15406)
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)		 Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM97724722 ZXDB liver,NS,carcinoma,hepatocellular carcinoma c.1308C>A p.D436E 23:57593356-57593356 12
2 COSM94436083 ZSWIM1 liver,NS,carcinoma,hepatocellular carcinoma c.1399A>C p.S467R 20:45883991-45883991 12
3 COSM94063771 ZSCAN20 liver,NS,carcinoma,hepatocellular carcinoma c.2314G>T p.G772W 1:33494658-33494658 12
4 COSM88264637 ZRSR2 liver,NS,carcinoma,hepatocellular carcinoma c.304G>T p.E102* 23:15803788-15803788 12
5 COSM131494492 ZNRF3 liver,NS,carcinoma,hepatocellular carcinoma c.1159A>G p.M387V 22:29049340-29049340 12
6 COSM102131817 ZNFX1 liver,NS,carcinoma,hepatocellular carcinoma c.2580G>A p.L860= 20:49257501-49257501 12
7 COSM113317148 ZNF853 liver,NS,carcinoma,hepatocellular carcinoma c.1610G>T p.G537V 7:6622601-6622601 12
8 COSM128686611 ZNF829 liver,NS,carcinoma,hepatocellular carcinoma c.1072T>A p.F358I 19:36891962-36891962 12
9 COSM123949383 ZNF827 liver,NS,carcinoma,hepatocellular carcinoma c.1741C>T p.L581= 4:145885684-145885684 12
10 COSM86004822 ZNF653 liver,NS,carcinoma,hepatocellular carcinoma c.1553A>C p.H518P 19:11485673-11485673 12
11 COSM139729931 ZNF615 liver,NS,carcinoma,hepatocellular carcinoma c.141G>A p.V47= 19:52002156-52002156 12
12 COSM91868668 ZNF536 liver,NS,carcinoma,hepatocellular carcinoma c.3900G>T p.K1300N 19:30557161-30557161 12
13 COSM91880764 ZNF536 liver,NS,carcinoma,hepatocellular carcinoma c.2171-78T>G p.? 19:30534769-30534769 12
14 COSM94799980 ZNF521 liver,NS,carcinoma,hepatocellular carcinoma c.3658+205G>A p.? 18:25194955-25194955 12
15 COSM90582798 ZNF518B liver,NS,carcinoma,hepatocellular carcinoma c.1624G>T p.E542* 4:10444705-10444705 12
16 COSM87577038 ZNF462 liver,NS,carcinoma,hepatocellular carcinoma c.6715G>T p.V2239L 9:106974156-106974156 12
17 COSM151538615 ZNF385B liver,NS,carcinoma,hepatocellular carcinoma c.253+23785G>T p.? 2:179745718-179745718 12
18 COSM111609487 ZNF276 liver,NS,carcinoma,hepatocellular carcinoma c.1444C>G p.L482V 16:89734008-89734008 12
19 COSM92353291 ZNF26 liver,NS,carcinoma,hepatocellular carcinoma c.1010C>T p.T337I 12:133010889-133010889 12
20 COSM95253159 ZNF217 liver,NS,carcinoma,hepatocellular carcinoma c.*194A>T p.? 20:53569094-53569094 12
21 COSM94505616 ZMYND12 liver,NS,carcinoma,hepatocellular carcinoma c.425-1G>T p.? 1:42440026-42440026 12
22 COSM89943752 ZMYM4 liver,NS,carcinoma,hepatocellular carcinoma c.86-8201G>T p.? 1:35350724-35350724 12
23 COSM101398456 ZIC2 liver,NS,carcinoma,hepatocellular carcinoma c.-18C>T p.? 13:99982047-99982047 12
24 COSM92703312 ZGPAT liver,NS,carcinoma,hepatocellular carcinoma c.*197C>A p.? 20:63736116-63736116 12
25 COSM92032561 ZFYVE26 liver,NS,carcinoma,hepatocellular carcinoma c.663C>A p.A221= 14:67807621-67807621 12
26 COSM84360265 ZFR liver,NS,carcinoma,hepatocellular carcinoma c.1979+14C>A p.? 5:32395145-32395145 12
27 COSM84362097 ZFR liver,NS,carcinoma,hepatocellular carcinoma c.2882C>T p.P961L 5:32364229-32364229 12
28 COSM85178149 ZFP36L2 liver,NS,carcinoma,hepatocellular carcinoma c.910T>G p.S304A 2:43224894-43224894 12
29 COSM87884183 ZFP28 liver,NS,carcinoma,hepatocellular carcinoma c.1865G>A p.C622Y 19:56554650-56554650 12
30 COSM127392053 ZFHX4 liver,NS,carcinoma,hepatocellular carcinoma c.10601C>G p.S3534C 8:76864315-76864315 12
31 COSM149268658 ZFHX3 liver,NS,carcinoma,hepatocellular carcinoma c.9997C>T p.Q3333* 16:72788279-72788279 12
32 COSM149328017 ZFHX3 liver,NS,carcinoma,hepatocellular carcinoma c.10852C>A p.P3618T 16:72787424-72787424 12
33 COSM149281099 ZFHX3 liver,NS,carcinoma,hepatocellular carcinoma c.8342A>G p.Q2781R 16:72794340-72794340 12
34 COSM144309108 ZEB2 liver,NS,carcinoma,hepatocellular carcinoma c.1141A>G p.M381V 2:144400046-144400046 12
35 COSM87420403 ZCCHC14 liver,NS,carcinoma,hepatocellular carcinoma c.71A>T p.Q24L 16:87491757-87491757 12
36 COSM98996636 ZC3H7A liver,NS,carcinoma,hepatocellular carcinoma c.2866A>G p.N956D 16:11751367-11751367 12
37 COSM92255466 ZC3H15 liver,NS,carcinoma,hepatocellular carcinoma c.*55T>G p.? 2:186508788-186508788 12
38 COSM85044193 ZC3H14 liver,NS,carcinoma,hepatocellular carcinoma c.*10873G>A p.? 14:88622624-88622624 12
39 COSM106743522 ZBTB7B liver,NS,carcinoma,hepatocellular carcinoma c.*635G>C p.? 1:155017320-155017320 12
40 COSM93795261 ZBTB41 liver,NS,carcinoma,hepatocellular carcinoma c.1700G>A p.R567K 1:197178489-197178489 12
41 COSM103188148 ZBTB40 liver,NS,carcinoma,hepatocellular carcinoma c.3339C>A p.F1113L 1:22524258-22524258 12
42 COSM91488114 ZBTB4 liver,NS,carcinoma,hepatocellular carcinoma c.454G>T p.G152C 17:7466348-7466348 12
43 COSM95291738 ZBTB37 liver,NS,carcinoma,hepatocellular carcinoma c.620G>C p.S207T 1:173870845-173870845 12
44 COSM107993551 ZBTB10 liver,NS,carcinoma,hepatocellular carcinoma c.2383A>G p.I795V 8:80519295-80519295 12
45 COSM107993152 ZBTB10 liver,NS,carcinoma,hepatocellular carcinoma c.2208A>G p.T736= 8:80518852-80518852 12
46 COSM86073785 ZBED4 liver,NS,carcinoma,hepatocellular carcinoma c.2225A>C p.E742A 22:49885887-49885887 12
47 COSM142300159 YTHDF3 liver,NS,carcinoma,hepatocellular carcinoma c.1580A>G p.N527S 8:63187582-63187582 12
48 COSM90849676 YOD1 liver,NS,carcinoma,hepatocellular carcinoma c.*157T>C p.? 1:207048863-207048863 12
49 COSM90620829 YME1L1 liver,NS,carcinoma,hepatocellular carcinoma c.2006A>G p.H669R 10:27116230-27116230 12
50 COSM86902201 YEATS2 liver,NS,carcinoma,hepatocellular carcinoma c.501C>T p.N167= 3:183722100-183722100 12
Sources

Expression for Tyrosinemia, Type I

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Search GEO for disease gene expression data for Tyrosinemia, Type I.
Sources

Pathways for Tyrosinemia, Type I

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Pathways related to Tyrosinemia, Type I according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Metabolism 65
Show member pathways
 13.48 TYR TAT PCSK9 OTC NAGS HPD
2
Viral mRNA Translation 65
Show member pathways
 13.4 TYR TAT OTC NAGS HPD HGD
3
Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism 65
Show member pathways
 11.64 TAT HPD HGD GSTZ1 FAH
4
Amino Acid metabolism 1
11.54 TAT OTC FAH
5
Tyrosine metabolism 36
Show member pathways
 10.98 TYR TAT HPD HGD GSTZ1 FAH
6
Arginine biosynthesis 36
Show member pathways
 10.96 OTC NAGS ASL
7
Urea cycle and metabolism of amino groups 1
Show member pathways
 10.88 OTC NAGS ASL
8
Ubiquinol biosynthesis 65
Show member pathways
 10.79 TAT HPD
Sources

GO Terms for Tyrosinemia, Type I

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Cellular components related to Tyrosinemia, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.44 TYR TAT HPD HGD GSTZ1 GNMT
2 mitochondrial matrix GO:0005759 9.26 OTC NAGS GSTZ1 DGUOK

Biological processes related to Tyrosinemia, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular amino acid metabolic process GO:0006520 9.54 TAT OTC HGD
2 urea cycle GO:0000050 9.5 OTC NAGS ASL
3 glutamate metabolic process GO:0006536 9.46 TAT NAGS
4 aromatic amino acid family metabolic process GO:0009072 9.46 TAT HPD GSTZ1 FAH
5 response to mercury ion GO:0046689 9.43 TAT ALAD
6 arginine biosynthetic process GO:0006526 9.43 OTC NAGS ASL
7 arginine biosynthetic process via ornithine GO:0042450 9.4 OTC ASL
8 L-phenylalanine catabolic process GO:0006559 9.35 TAT HPD HGD GSTZ1 FAH
9 tyrosine catabolic process GO:0006572 9.02 TAT HPD HGD GSTZ1 FAH

Molecular functions related to Tyrosinemia, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 catalytic activity GO:0003824 9.35 TAT GSTZ1 FAH ASL ALAD
2 identical protein binding GO:0042802 9.32 TYR TAT SERPINA1 OTC HGD GSTZ1
3 amino acid binding GO:0016597 9.16 TAT OTC
Sources

Sources for Tyrosinemia, 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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