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MCID: CLS049
MIFTS: 42

Classic Phenylketonuria

Categories: Metabolic diseases, Neuronal diseases, Rare diseases
Genes Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Classic Phenylketonuria

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MalaCards integrated aliases for Classic Phenylketonuria:

Name: Classic Phenylketonuria 59
Phenylketonuria Classical 55
Classical Phenylketonuria 73
Classic Pku 59

Characteristics:

Orphanet epidemiological data:

59
classic phenylketonuria
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

Classifications:

MalaCards categories:
Global: Metabolic diseases Rare diseases
Anatomical: Neuronal diseases
See all MalaCards categories (disease lists)
ICD10: 34 33
Orphanet: 59  
Rare neurological diseases
Inborn errors of metabolism


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Summaries for Classic Phenylketonuria

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MalaCards based summary : Classic Phenylketonuria, also known as phenylketonuria classical, is related to phenylketonuria and mild phenylketonuria, and has symptoms including dry skin An important gene associated with Classic Phenylketonuria is PAH (Phenylalanine Hydroxylase), and among its related pathways/superpathways are Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism and Folate biosynthesis. The drugs Verapamil and Dopamine have been mentioned in the context of this disorder. Affiliated tissues include brain, skin and testes, and related phenotypes are depressivity and seizures

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Related Diseases for Classic Phenylketonuria

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Diseases related to Classic Phenylketonuria via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 16)
# Related Disease Score Top Affiliating Genes
1 phenylketonuria 30.6 PAH PTS QDPR
2 mild phenylketonuria 11.3
3 hyperphenylalaninemia, bh4-deficient, a 11.0
4 lobar holoprosencephaly 9.7
5 autism 9.7
6 leukemia, acute lymphoblastic 9.7
7 holoprosencephaly 9.7
8 leukemia 9.7
9 lymphoblastic leukemia 9.7
10 cerebritis 9.7
11 hyperphenylalaninemia, bh4-deficient, b 9.3 PTS QDPR
12 tyrosinemia 9.2 PAH PTS
13 keratomalacia 9.1 PAH QDPR
14 mild hyperphenylalaninemia 8.8 PAH PTS QDPR
15 tetrahydrobiopterin deficiency 8.8 PAH PTS QDPR
16 hyperphenylalaninemia 8.7 PAH PTS QDPR

Graphical network of the top 20 diseases related to Classic Phenylketonuria:



Diseases related to Classic Phenylketonuria
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Symptoms & Phenotypes for Classic Phenylketonuria

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Human phenotypes related to Classic Phenylketonuria:

59 32 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 depressivity 59 32 frequent (33%) Frequent (79-30%) HP:0000716
2 seizures 59 32 frequent (33%) Frequent (79-30%) HP:0001250
3 tremor 59 32 frequent (33%) Frequent (79-30%) HP:0001337
4 hyperreflexia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001347
5 nausea and vomiting 59 32 frequent (33%) Frequent (79-30%) HP:0002017
6 cerebral calcification 59 32 occasional (7.5%) Occasional (29-5%) HP:0002514
7 self-injurious behavior 59 32 occasional (7.5%) Occasional (29-5%) HP:0100716
8 cataract 59 32 occasional (7.5%) Occasional (29-5%) HP:0000518
9 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
10 microcephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000252
11 hypertonia 59 32 frequent (33%) Frequent (79-30%) HP:0001276
12 intellectual disability, severe 59 32 hallmark (90%) Very frequent (99-80%) HP:0010864
13 lack of skin elasticity 59 32 occasional (7.5%) Occasional (29-5%) HP:0100679
14 motor deterioration 59 32 occasional (7.5%) Occasional (29-5%) HP:0002333
15 autism 59 32 frequent (33%) Frequent (79-30%) HP:0000717
16 attention deficit hyperactivity disorder 59 32 frequent (33%) Frequent (79-30%) HP:0007018
17 growth delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001510
18 memory impairment 59 32 frequent (33%) Frequent (79-30%) HP:0002354
19 hypopigmentation of hair 59 32 hallmark (90%) Very frequent (99-80%) HP:0005599
20 eczema 59 32 frequent (33%) Frequent (79-30%) HP:0000964
21 hemiplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002301
22 hypopigmentation of the skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0001010
23 paraplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0010550
24 hyperphenylalaninemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0004923
25 behavioral abnormality 59 Very frequent (99-80%)
26 mental deterioration 59 Frequent (79-30%)

UMLS symptoms related to Classic Phenylketonuria:


dry skin

MGI Mouse Phenotypes related to Classic Phenylketonuria:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 pigmentation MP:0001186 8.62 PAH PTS
Sources

Drugs & Therapeutics for Classic Phenylketonuria

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Drugs for Classic Phenylketonuria (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 68)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Verapamil Approved Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable 52-53-9 2520
2
Dopamine Approved Phase 4 51-61-6, 62-31-7 681
3
Benzocaine Approved, Investigational Phase 4 1994-09-7, 94-09-7 2337
4
Melatonin Approved, Nutraceutical, Vet_approved Phase 4 73-31-4 896
5 tannic acid Approved, Nutraceutical Phase 4
6 calcium channel blockers Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable
7 Neurotransmitter Agents Phase 4,Not Applicable
8 Anti-Arrhythmia Agents Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable
9 Vasodilator Agents Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable
10 Calcium, Dietary Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable
11 Central Nervous System Depressants Phase 4
12 Serotonin Agents Phase 4
13 Dopamine Agents Phase 4
14 Pharmaceutical Solutions Phase 4
15 Antioxidants Phase 4
16 Protective Agents Phase 4
17 phenylalanine Nutraceutical Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable
18
Serotonin Investigational, Nutraceutical Phase 4 50-67-9 5202
19 Dextrans Phase 3
20
Nitric Oxide Approved Phase 2 10102-43-9 145068 160954
21
leucovorin Approved, Nutraceutical Phase 2 58-05-9 143 6006
22
Folic Acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
23 Micronutrients Phase 2,Not Applicable
24 Trace Elements Phase 2,Not Applicable
25 Vitamins Phase 2,Not Applicable
26 Hematinics Phase 2
27 Vitamin B Complex Phase 2
28 Liver Extracts Phase 1, Phase 2
29 Folate Nutraceutical Phase 2
30 Vitamin B9 Nutraceutical Phase 2
31
Moxifloxacin Approved, Investigational Phase 1 354812-41-2, 151096-09-2 152946
32 Estradiol valerate Approved, Investigational, Vet_approved Phase 1 979-32-8
33
Norgestimate Approved, Investigational Phase 1 35189-28-7 6540478
34
Estradiol Approved, Investigational, Vet_approved Phase 1 50-28-2 5757
35
Ethinyl Estradiol Approved Phase 1 57-63-6 5991
36
Polyestradiol phosphate Approved Phase 1 28014-46-2
37 Fluoroquinolones Phase 1
38 Contraceptive Agents Phase 1
39 Contraceptives, Oral Phase 1
40 Contraceptives, Oral, Combined Phase 1
41 Topoisomerase Inhibitors Phase 1
42 Norgestimate, ethinyl estradiol drug combination Phase 1
43 Nucleic Acid Synthesis Inhibitors Phase 1
44 Anti-Bacterial Agents Phase 1
45 Estradiol 17 beta-cypionate Phase 1
46 Estradiol 3-benzoate Phase 1
47 Anti-Infective Agents Phase 1,Not Applicable
48
Menthol Approved 2216-51-5 16666
49
Coal tar Approved Not Applicable 8007-45-2
50 Fluorodeoxyglucose F18 Not Applicable

Interventional clinical trials:

(show top 50) (show all 82)
# Name Status NCT ID Phase Drugs
1 Response to Kuvan® in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period Completed NCT01082328 Phase 4 Kuvan®
2 Effects of Kuvan on Melatonin Secretion Completed NCT01617070 Phase 4 Kuvan
3 The Effectiveness of Kuvan in Amish PKU Patients Recruiting NCT02677870 Phase 4 saproterin dihydrochloride
4 Kuvan®'s Effect on the Cognition of Children With Phenylketonuria Active, not recruiting NCT01965912 Phase 4 Kuvan®
5 Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria Completed NCT01732471 Phase 3 Kuvan®
6 Kuvan® in Phenylketonuria Patients Less Than 4 Years Old Completed NCT01376908 Phase 3 Kuvan®
7 Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006 Completed NCT00332189 Phase 3 sapropterin dihydrochloride
8 Study to Evaluate the Safety and Efficacy of Phenoptinâ„¢ in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels Completed NCT00104247 Phase 3 sapropterin dihydrochloride, 6R-BH4, tetrahydrobiopterin
9 Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients Completed NCT01114737 Phase 3 Sapropterin dihydrochloride;Placebo
10 Study of Phenoptin to Increase Phenylalanine Tolerance in Phenylketonuric Children on a Phenylalanine-restricted Diet Completed NCT00272792 Phase 3 Sapropterin Dihydrochloride;Placebo
11 A Phase 3, Multicenter, Open-Label Extension Study of Phenoptin in Subjects With PKU Who Have Elevated Phenylalanine Levels Completed NCT00225615 Phase 3 sapropterin dihydrochloride
12 An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165 Completed NCT01819727 Phase 3 BMN 165
13 Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU Active, not recruiting NCT00838435 Phase 3 sapropterin dihydrochloride
14 Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU Active, not recruiting NCT01889862 Phase 3 BMN165 20mg/day;BMN165 40mg/day;Placebo
15 Long-Term Tetrahydrobiopterin Treatment in PKU Patients of 0-18 Years - Study on Phenylalanine Tolerance and Safety Terminated NCT00432822 Phase 2, Phase 3 tetrahydrobiopterin (BH4)
16 Study to Evaluate the Response to and Safety of an 8-Day Course of Phenoptinâ„¢ Treatment in Subjects With Phenylketonuria Completed NCT00104260 Phase 2 sapropterin dihydrochloride
17 Safety, Tolerability, and Efficacy Study of rAvPAL-PEG Administered Daily in Subjects With Phenylketonuria (PKU) Completed NCT01212744 Phase 2 rAvPAL-PEG
18 A Study to Evaluate Subcutaneously Administered rAvPAL-PEG in Patients With Phenylketonuria for 24 Weeks Completed NCT01560286 Phase 2
19 Dose-Finding Study to Evaluate the Safety, Efficacy, & Tolerability of Multiple Doses of rAvPAL-PEG in Subjects With PKU Completed NCT00925054 Phase 2 rAvPAL-PEG
20 Study of BH4, a New and Simple Treatment of Mild PKU Completed NCT00260000 Phase 2 5,6,7,8-tetrahydrobiopterin
21 Safety and Efficacy Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to BH4 Deficiency Completed NCT00355264 Phase 2 Phenoptin
22 Safety and Tolerability of SYNB1618 in Healthy Adult Volunteers and Adult Subjects With Phenylketonuria Recruiting NCT03516487 Phase 1, Phase 2 SYNB1618;Placebo
23 Neurovascular Transduction During Exercise in Chronic Kidney Disease Recruiting NCT02947750 Phase 2 6R-BH4
24 Long-Term Extension of Previous rAvPAL-PEG Protocols in Subjects With PKU (PAL-003) Active, not recruiting NCT00924703 Phase 2 rAvPAL-PEG
25 A Study of CNSA-001 in Primary Tetrahydrobiopterin Deficient Patients With Hyperphenylalaninemia Not yet recruiting NCT03519711 Phase 1, Phase 2 CNSA-001
26 Liver Cell Transplant for Phenylketonuria Suspended NCT01465100 Phase 1, Phase 2 Immunosuppression
27 Sapropterin on Cognitive Abilities in Young Adults With Phenylketonuria Terminated NCT01977820 Phase 2 Sapropterin;Placebo
28 Phenylketonuria, Oxidative Stress, and BH4 Terminated NCT01395394 Phase 2 Kuvan
29 Response to Phenylketonuria to Tetrahydrobiopterin (BH4) Unknown status NCT00244218 Phase 1 tetrahydrobiopterin (BH4)
30 Safety and Tolerability Study of rAvPAL-PEG to Treat Phenylketonuria Completed NCT00634660 Phase 1 rAvPAL-PEG
31 A Phase 1 Study to Evaluate Effects of Sapropterin Dihydrochloride on QTc Intervals in Healthy Adult Subjects Completed NCT00789568 Phase 1 sapropterin dihydrochloride;Moxifloxacin
32 Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response Unknown status NCT00841100 Not Applicable Kuvan
33 Evaluation of Behavior, Executive Function, Neurotransmitter Function and Genomic Expression Kuvan Nonresponders Unknown status NCT01274026 Not Applicable sapropterin dihydrochloride
34 Sapropterin Expanded Access Program Approved for marketing NCT00484991 Sapropterin dihydrochloride
35 Observational Study of Endothelial Dysfunction in Phenylketonuria Completed NCT02176603
36 Impact of Phenylketonuria-type Diet on Appetite, Appetite Hormones and Diet Induced Thermogenesis Completed NCT02440932 Not Applicable
37 Sapropterin in Individuals With Phenylketonuria Completed NCT00730080 Sapropterin (Kuvan)
38 Protein Requirements in Children With Phenylketonuria (PKU) Completed NCT01965691 Not Applicable
39 The Brain, Neurological Features and Neuropsychological Functioning in Adults With Phenylketonuria: A Pilot Study Completed NCT01917344 Not Applicable
40 Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria Completed NCT00909012 Not Applicable
41 Simplified Diet Approach in Phenylketonuria Completed NCT02555579 Not Applicable
42 The Brain and Neuropsychological Functioning in Adults With Sapropterin Dihydrochloride Treated Phenylketonuria Completed NCT02297347
43 Fluorodeoxyglucose Positron Emission Tomography (FDG PET) Findings in Patients With Phenylketonuria Before and After KUVAN Therapy Completed NCT00986973 Not Applicable Sapropterin
44 Phenylketonuria and Hyperphenylalaninemia Nutrition Study Completed NCT01879995
45 Study to Evaluate the Effects of Kuvan on Individuals With Phenylketonuria (PKU) With Maladaptive Behaviors Completed NCT00728676
46 Educational, Social Support, and Nutritional Interventions and Their Cumulative Effect on Pregnancy Outcomes and Quality of Life in Teen and Adult Women With Phenylketonuria Completed NCT01659749 Not Applicable
47 The Effects of Kuvan on Functional Brain Connectivity in Individuals With Phenylketonuria (PKU) Completed NCT00964236 Sapropterin
48 Low Phenylalanine Diet for Mothers With Phenylketonuria (PKU) Completed NCT00065299 Not Applicable
49 Simple Breath Test to Examine Phenylalanine Metabolism Completed NCT02009904
50 The Effect of Supplemental Docosahexaenoic Acid (DHA) on Neurocognitive Outcomes in Teen and Adult Women With Phenylketonuria(PKU) Completed NCT00892554 Not Applicable

Search NIH Clinical Center for Classic Phenylketonuria

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Genetic Tests for Classic Phenylketonuria

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Anatomical Context for Classic Phenylketonuria

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MalaCards organs/tissues related to Classic Phenylketonuria:

41
Brain, Skin, Testes, Liver, Bone, Kidney, Endothelial
Sources

Publications for Classic Phenylketonuria

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Articles related to Classic Phenylketonuria:

(show all 35)
# Title Authors Year
1
Vitamin/mineral and micronutrient status in patients with classical phenylketonuria. ( 29433755 )
2018
2
Successful Linkage Analysis in Classical Phenylketonuria Families Followed by Direct Sequencing and Mutation Detection. ( 27156318 )
2016
3
Demethylation of the promoter region of GPX3 in a newborn with classical phenylketonuria. ( 27742442 )
2016
4
[The mutation analysis of PAH gene and prenatal diagnosis in classical phenylketonuria family]. ( 25449068 )
2014
5
Long-term outcomes of blood phenylalanine concentrations in children with classical phenylketonuria. ( 23465864 )
2013
6
[Detection of exon 7 mutations of PAH gene in classical phenylketonuria by high-resolution melting analysis]. ( 23225049 )
2012
7
Free asymmetric dimethylarginine (ADMA) is low in children and adolescents with classical phenylketonuria (PKU). ( 22290024 )
2012
8
Blood phenylalanine clearance and BH(4)-responsiveness in classic phenylketonuria. ( 21592835 )
2011
9
Brain MRI diffusion-weighted imaging in patients with classical phenylketonuria. ( 19652961 )
2009
10
Prevalence of classical phenylketonuria in mentally retarded individuals in Iran. ( 19768570 )
2009
11
Total homocysteine, B-vitamins and genetic polymorphisms in patients with classical phenylketonuria. ( 18249021 )
2008
12
Growth and body composition in children with classical phenylketonuria: results in 34 patients and review of the literature. ( 17628756 )
2007
13
Successful neurological outcome of a child with classical phenylketonuria and acute lymphoblastic leukemia: a 7-year follow-up. ( 17480007 )
2007
14
Cerebral glucose metabolism in adults with early treated classic phenylketonuria. ( 16343970 )
2006
15
[Identification of novel mutations in the phenylalanine hydroxylase gene of classical phenylketonuria]. ( 15793771 )
2005
16
Long-term treatment of patients with mild and classical phenylketonuria by tetrahydrobiopterin. ( 16242984 )
2005
17
Cognitive functions in classic phenylketonuria and mild hyperphenylalaninaemia: experience in a paediatric population. ( 15991863 )
2005
18
Development of pegylated forms of recombinant Rhodosporidium toruloides phenylalanine ammonia-lyase for the treatment of classical phenylketonuria. ( 15922970 )
2005
19
Lobar holoprosencephaly in an infant born to a mother with classic phenylketonuria. ( 11078575 )
2000
20
Two novel mutations in exon 11 of the PAH gene (1163/1164 del TG and P362T) associated with classic phenylketonuria and mild phenylketonuria. ( 10200057 )
1998
21
Expression of human phenylalanine hydroxylase activity in T lymphocytes of classical phenylketonuria children by retroviral-mediated gene transfer. ( 9427141 )
1997
22
[DNA analysis in classic phenylketonuria--screening for mutations and haplotype analysis in Slovak families]. ( 7812811 )
1994
23
Treatment variables and intellectual outcome in children with classic phenylketonuria. A single-center-based study. ( 8365077 )
1993
24
Heterozygous carriers of classical phenylketonuria in a sample of the Turkish population: detection by a spectrofluorimetric method. ( 1843186 )
1991
25
Significant phenylalanine hydroxylation in vivo in patients with classical phenylketonuria. ( 2365821 )
1990
26
A Chinese classic phenylketonuria manifested as autism. ( 2597924 )
1989
27
A simple method for detection of heterozygous carriers of the gene for classic phenylketonuria. ( 3761073 )
1986
28
Study of serum ferritin in 58 children with classic phenylketonuria and persistent hyperphenylalaninaemia. ( 3939594 )
1985
29
Prenatal diagnosis of classic phenylketonuria by DNA analysis. ( 2857902 )
1985
30
Amino acid and protein requirements in a preterm infant with classic phenylketonuria. ( 3985660 )
1985
31
Prenatal diagnosis and carrier detection of classic phenylketonuria by gene analysis. ( 6472974 )
1984
32
Neurophysiological, psychological, and nutritional investigations during discontinuation of the phenylalanine-restricted diet in children with classic phenylketonuria. ( 6615595 )
1983
33
Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria. ( 6316140 )
1983
34
Classic phenylketonuria: diagnosis through heterozygote detection. ( 1127497 )
1975
35
Classic phenylketonuria: heterozygote detection during pregnancy. ( 4773479 )
1973
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Variations for Classic Phenylketonuria

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Expression for Classic Phenylketonuria

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Search GEO for disease gene expression data for Classic Phenylketonuria.
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Pathways for Classic Phenylketonuria

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Pathways related to Classic Phenylketonuria according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism 66
Show member pathways
 11.05 PAH QDPR
2
Folate biosynthesis 37
Show member pathways
 10.26 PAH PTS QDPR
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GO Terms for Classic Phenylketonuria

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Biological processes related to Classic Phenylketonuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular amino acid metabolic process GO:0006520 9.16 PTS QDPR
2 L-phenylalanine catabolic process GO:0006559 8.96 PAH QDPR
3 tetrahydrobiopterin biosynthetic process GO:0006729 8.62 PTS QDPR
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Sources for Classic Phenylketonuria

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 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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