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PKU
MCID: PHN003
MIFTS: 75

Phenylketonuria (PKU)

Categories: Fetal diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
Sources

Aliases & Classifications for Phenylketonuria

About this section

MalaCards integrated aliases for Phenylketonuria:

Name: Phenylketonuria 56 12 74 52 25 58 73 36 29 13 6 42 15 37 39
Phenylalanine Hydroxylase Deficiency 56 74 24 52 25 58
Pku 56 12 52 25 58 73
Pah Deficiency 56 24 25 58
Maternal Phenylketonuria 12 58 29
Phenylketonurias 54 43 71
Folling Disease 56 52 25
Oligophrenia Phenylpyruvica 56 52
Phenylketonuria, Maternal 43 71
Classical Phenylketonuria 71 32
Variant Phenylketonuria 52 58
Mild Phenylketonuria 52 58
Folling's Disease 12 25
Phenylalaninemia 12 74
Variant Pku 52 58
Mild Pku 52 58
Mpku 52 58
Deficiency Disease, Phenylalanine Hydroxylase 25
Phenylalanine Hydroxylase Deficiency Disease 25
Non-Phenylketonuria Hyperphenylalaninemia 73
Hyperphenylalaninemia, Non-Pku Mild 56
Hyperphenylalaninemic Embryopathy 58
Maternal Hyperphenylalaninemia 58
Phenylketonuric Embryopathy 58
Phenylketonuria Maternal 54
Hyperphenylalaninaemia 71
Hyperphenylalaninemia 73
Maternal Pku 58
Non-Pku Hpa 73
Hpa 73

Characteristics:

Orphanet epidemiological data:

58
phenylketonuria
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (France),1-5/10000 (Ireland),1-9/1000000 (Finland),1-5/10000 (Turkey); Age of onset: Infancy; Age of death: normal life expectancy;
maternal phenylketonuria
Inheritance: Autosomal recessive; Prevalence: 1-5/10000 (Europe); Age of onset: Antenatal,Neonatal;
mild phenylketonuria
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
occurs in about 1 in 10,000 births
mousy odor


HPO:

31
phenylketonuria:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases Fetal diseases
Anatomical: Neuronal diseases
See all MalaCards categories (disease lists)
ICD10: 32 33
Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism
Developmental anomalies during embryogenesis
Teratologic disorders


Sources

Summaries for Phenylketonuria

About this section
Genetics Home Reference : 25 Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners. If PKU is not treated, phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems. The signs and symptoms of PKU vary from mild to severe. The most severe form of this disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old. Without treatment, these children develop permanent intellectual disability. Seizures, delayed development, behavioral problems, and psychiatric disorders are also common. Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members and are also likely to have skin disorders such as eczema. Less severe forms of this condition, sometimes called variant PKU and non-PKU hyperphenylalaninemia, have a smaller risk of brain damage. People with very mild cases may not require treatment with a low-phenylalanine diet. Babies born to mothers who have PKU and uncontrolled phenylalanine levels (women who no longer follow a low-phenylalanine diet) have a significant risk of intellectual disability because they are exposed to very high levels of phenylalanine before birth. These infants may also have a low birth weight and grow more slowly than other children. Other characteristic medical problems include heart defects or other heart problems, an abnormally small head size (microcephaly), and behavioral problems. Women with PKU and uncontrolled phenylalanine levels also have an increased risk of pregnancy loss.

MalaCards based summary : Phenylketonuria, also known as phenylalanine hydroxylase deficiency, is related to classic phenylketonuria and hyperphenylalaninemia, bh4-deficient, b, and has symptoms including seizures, dry skin and tremor. An important gene associated with Phenylketonuria is PAH (Phenylalanine Hydroxylase), and among its related pathways/superpathways are Phenylalanine, tyrosine and tryptophan biosynthesis and Folate biosynthesis. The drugs Dopamine and tannic acid have been mentioned in the context of this disorder. Affiliated tissues include Liver, brain and testes, and related phenotypes are aminoaciduria and intellectual disability

Disease Ontology : 12 An amino acid metabolic disorder that is characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional.

NIH Rare Diseases : 52 Mild phenylketonuria is a rare form of phenylketouria (PKU variant), an inborn error of amino acid metabolism , characterized by symptoms of PKU of mild to moderate severity. Patients with blood phenylalanine concentrations of 600-1,200 micromol/L are considered to have mild PKU. Clinical signs include reduced cognitive function and behavioral and developmental disorders. It is caused by certain mutations in the PAH gene which result in slightly higher activity of the phenylalanine hydroxylase compared with the classic phenylketonuria where there is a complete or near-complete deficiency of phenylalanine hydroxylase activity. Inheritance is autosomal recessive . Treatment is with a diet low in phenylalanine (patients can have up to 400-600 mg/day of phenylalanine).

OMIM : 56 Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism resulting from a deficiency of phenylalanine hydroxylase (PAH; 612349), an enzyme that catalyzes the hydroxylation of phenylalanine to tyrosine, the rate-limiting step in phenylalanine catabolism. If undiagnosed and untreated, phenylketonuria can result in impaired postnatal cognitive development resulting from a neurotoxic effect of hyperphenylalaninemia (Zurfluh et al., 2008). See Scriver (2007) and Blau et al. (2010) for detailed reviews of PKU. (261600)

MedlinePlus : 42 Phenylketonuria (PKU) is a type of amino acid metabolism disorder. It is inherited. If you have it, your body can't process part of a protein called phenylalanine (Phe). Phe is in almost all foods. If your Phe level gets too high, it can damage your brain and cause severe intellectual disability. All babies born in U.S. hospitals must now have a screening test for PKU. This makes it easier to diagnose and treat the problem early. The best treatment for PKU is a diet of low-protein foods. There are special formulas for newborns. For older children and adults, the diet includes many fruits and vegetables. It also includes some low-protein breads, pastas and cereals. Nutritional formulas provide the vitamins and minerals you can't get from their food. Babies who get on this special diet soon after they are born develop normally. Many have no symptoms of PKU. It is important to stay on the diet for the rest of your life. NIH: National Institute of Child Health and Human Development

KEGG : 36 Phenylketonuria (PKU) is one of the most common inborn errors of metabolism marked by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH), leading to a toxic accumulation of phenylalanine in the blood and multiple tissues and potentially to intellectual disability, delayed speech, seizures, and behavior abnormalities. Deficiency of tetrahydrobiopterin (BH4), the cofactor of PAH, is caused by defects of the enzymes in pterin biosynthesis. Because BH4 is also a cofactor of tyrosine hydroxylase and tryptophan hydroxylase in neurotransmitter synthesis, BH4-deficient hyperphenylalaninemia is characterized by neurotransmitter deficiencies.

UniProtKB/Swiss-Prot : 73 Hyperphenylalaninemia: Mildest form of phenylalanine hydroxylase deficiency.
Non-phenylketonuria hyperphenylalaninemia: Mild form of phenylalanine hydroxylase deficiency characterized by phenylalanine levels persistently below 600 mumol, which allows normal intellectual and behavioral development without treatment. Non-PKU HPA is usually caused by the combined effect of a mild hyperphenylalaninemia mutation and a severe one.
Phenylketonuria: Autosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol (normal concentration 100 mumol) which usually causes mental retardation (unless low phenylalanine diet is introduced early in life). They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor.

Wikipedia : 74 Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino... more...

GeneReviews: NBK1504
Sources

Related Diseases for Phenylketonuria

About this section

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

(show top 50) (show all 568)
# Related Disease Score Top Affiliating Genes
1 classic phenylketonuria 34.8 QDPR PTS PAH
2 hyperphenylalaninemia, bh4-deficient, b 33.8 TH QDPR PTS GCH1
3 segawa syndrome, autosomal recessive 33.1 TH GCH1
4 dystonia, dopa-responsive, due to sepiapterin reductase deficiency 33.1 QDPR PCBD1 GCH1
5 hyperphenylalaninemia, bh4-deficient, a 32.9 QDPR PTS PCBD1 PAH GCH1
6 hyperphenylalaninemia 32.5 TPH1 TH QDPR PTS PCBD1 PAH
7 amino acid metabolic disorder 31.9 PAH OTC MTHFR HPD BTD ALB
8 mild hyperphenylalaninemia 31.5 QDPR PTS PCBD1 PAH
9 congenital hypothyroidism 31.0 BTD ALB ACADM
10 tetrahydrobiopterin deficiency 30.6 TH QDPR PTS PCBD1 PAH GCH1
11 abdominal obesity-metabolic syndrome 1 30.5 PAH OTC GHRL BTD ACADM
12 psychotic disorder 30.5 TPH1 TH PAH MTHFR
13 anemia, x-linked, with or without neutropenia and/or platelet abnormalities 30.4 TTR G6PD ALB
14 dystonia 30.4 TPH1 TH QDPR PTS PCBD1 PAH
15 tyrosinemia 30.4 QDPR PTS PAH OTC HPD BTD
16 constipation 30.4 TPH1 TH GHRL ALB
17 sickle cell anemia 30.4 MTHFR G6PD ALB
18 enteropathica 30.3 OTC ALB
19 nutritional deficiency disease 30.2 TTR MTHFR GHRL BGLAP ALB
20 diabetes mellitus 30.2 TTR TH PTS MTHFR GHRL G6PD
21 chronic kidney disease 30.2 TTR MTHFR GHRL BGLAP ALB
22 anorexia nervosa 30.1 TTR TPH1 GHRL BGLAP
23 galactosemia iii 30.1 G6PD BTD ACADM
24 maple syrup urine disease 30.0 SLC7A5 QDPR PAH OTC HADHA BTD
25 lipoid congenital adrenal hyperplasia 29.9 HADHA BTD ACADM
26 acyl-coa dehydrogenase, medium-chain, deficiency of 29.9 PAH HADHA BTD ACADM
27 homocystinuria 29.9 OTC MTHFR HADHA BTD ALB ADSL
28 glycogen storage disease 29.8 OTC MTHFR BTD ALB
29 parkinson disease, late-onset 29.8 TTR TPH1 TH QDPR PAH GCH1
30 citrullinemia, classic 29.7 OTC HADHA ACADM
31 metabolic acidosis 29.7 BTD BGLAP ALB
32 diabetes mellitus, noninsulin-dependent 29.6 TTR TH PTS PCBD1 MTHFR GHRL
33 hyperphenylalaninemia, bh4-deficient, d 12.8
34 hyperphenylalaninemia, mild, non-bh4-deficient 12.7
35 hpa i recognition polymorphism, beta-globin-related 12.4
36 tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria 12.3
37 maternal hyperphenylalaninemia 12.2
38 gtp cyclohydrolase 1-deficient dopa-responsive dystonia 12.0
39 hyperphenylalaninemia, bh4-deficient, c 11.8
40 microcephaly 11.6
41 spasticity 11.5
42 dystonia, dopa-responsive 11.3
43 tyrosine-oxidase temporary deficiency 11.2
44 glycine encephalopathy 11.2
45 disorder of phenylalanine metabolism 10.8
46 inherited metabolic disorder 10.6
47 meningococcal infection 10.6 TTR G6PD
48 hereditary dystonia 10.6 TH GCH1
49 hypothyroidism 10.6
50 autosomal recessive disease 10.6

Graphical network of the top 20 diseases related to Phenylketonuria:



Diseases related to Phenylketonuria
Sources

Symptoms & Phenotypes for Phenylketonuria

About this section

Human phenotypes related to Phenylketonuria:

58 31 (show top 50) (show all 60)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 aminoaciduria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003355
2 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
3 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
4 abnormal facial shape 58 31 frequent (33%) Frequent (79-30%) HP:0001999
5 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
6 intellectual disability, severe 58 31 frequent (33%) Frequent (79-30%) HP:0010864
7 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
8 coarctation of aorta 58 31 frequent (33%) Frequent (79-30%) HP:0001680
9 hypoplastic left heart 58 31 frequent (33%) Frequent (79-30%) HP:0004383
10 wide nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0000431
11 anteverted nares 58 31 occasional (7.5%) Occasional (29-5%) HP:0000463
12 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
13 micrognathia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000347
14 tetralogy of fallot 58 31 occasional (7.5%) Occasional (29-5%) HP:0001636
15 long philtrum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000343
16 ventricular septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001629
17 hypoplasia of the corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002079
18 hyperactivity 58 31 occasional (7.5%) Occasional (29-5%) HP:0000752
19 double outlet right ventricle 58 31 occasional (7.5%) Occasional (29-5%) HP:0001719
20 abnormality of cardiovascular system morphology 31 occasional (7.5%) HP:0030680
21 seizure 31 occasional (7.5%) HP:0001250
22 strabismus 58 31 very rare (1%) Very rare (<4-1%) HP:0000486
23 epicanthus 58 31 very rare (1%) Very rare (<4-1%) HP:0000286
24 brachydactyly 58 31 very rare (1%) Very rare (<4-1%) HP:0001156
25 hypotelorism 58 31 very rare (1%) Very rare (<4-1%) HP:0000601
26 esophageal atresia 58 31 very rare (1%) Very rare (<4-1%) HP:0002032
27 sloping forehead 58 31 very rare (1%) Very rare (<4-1%) HP:0000340
28 abnormal renal morphology 58 31 very rare (1%) Very rare (<4-1%) HP:0012210
29 clinodactyly 58 31 very rare (1%) Very rare (<4-1%) HP:0030084
30 bladder exstrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0002836
31 deviated nasal septum 58 31 very rare (1%) Very rare (<4-1%) HP:0004411
32 bilateral ptosis 58 31 very rare (1%) Very rare (<4-1%) HP:0001488
33 bifid distal phalanx of the thumb 58 31 very rare (1%) Very rare (<4-1%) HP:0009611
34 hypoplastic helices 58 31 very rare (1%) Very rare (<4-1%) HP:0008589
35 cataract 31 HP:0000518
36 seizures 58 Occasional (29-5%)
37 irritability 31 HP:0000737
38 malformation of the heart and great vessels 58 Occasional (29-5%)
39 dry skin 31 HP:0000958
40 hyperreflexia 31 HP:0001347
41 attention deficit hyperactivity disorder 31 HP:0007018
42 anxiety 31 HP:0000739
43 depressivity 31 HP:0000716
44 blue irides 31 HP:0000635
45 obsessive-compulsive behavior 31 HP:0000722
46 generalized hypopigmentation 31 HP:0007513
47 eczema 31 HP:0000964
48 psychosis 31 HP:0000709
49 cerebral calcification 31 HP:0002514
50 abnormal heart morphology 58 Very frequent (99-80%)

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
microcephaly

Metabolic Features:
hyperphenylalaninemia
phenylpyruvic acidemia
phenylalanine hydroxylase deficiency

Skin Nails Hair Hair:
blond hair

Neurologic Central Nervous System:
decreased mental processing speed
mental retardation (if left untreated)
infantile irritability (if left untreated)
peculiar gait (if left untreated)
peculiar stance and sitting posture (if left untreated)
more
Prenatal Manifestations Maternal:
maternal hyperphenylalaninemia teratogenic

Skin Nails Hair Skin:
dry skin
eczema
scleroderma
pale pigmentation

Neurologic Behavioral Psychiatric Manifestations:
depression
obsessive-compulsive disorder
psychosis (if left untreated)
hyperactivity (if left untreated)
autistic features (if left untreated)
more
Head And Neck Eyes:
blue eyes
cataracts

Neurologic Peripheral Nervous System:
defective myelin formation (if left untreated)

Laboratory Abnormalities:
increased urinary o-hydroxyphenylacetic acid, phenylpyruvic acid, phenylacetic acid and phenylacetylglutamine

Clinical features from OMIM:

261600

UMLS symptoms related to Phenylketonuria:


seizures, dry skin, tremor, back pain, headache, syncope, pain, chronic pain, sciatica, vertigo/dizziness, sleeplessness, morning sickness

GenomeRNAi Phenotypes related to Phenylketonuria according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00240-S-1 9.64 ADSL
2 Decreased viability GR00249-S 9.64 ACADM ALB G6PD GHRL PCBD1 SLC7A5
3 Decreased viability GR00381-A-1 9.64 GCH1
4 Decreased viability GR00386-A-1 9.64 ACADM ALB G6PD HADHA HPD MTHFR
5 Decreased viability GR00402-S-2 9.64 ACADM G6PD SLC7A5

MGI Mouse Phenotypes related to Phenylketonuria:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.23 ACADM ALB BGLAP BTD G6PD GCH1
2 cardiovascular system MP:0005385 10.02 ACADM ADSL ALB G6PD GCH1 HADHA
3 integument MP:0010771 9.81 ACADM BTD MTHFR OTC PAH PCBD1
4 pigmentation MP:0001186 9.35 BTD OTC PAH PCBD1 PTS
5 renal/urinary system MP:0005367 9.23 ALB BTD HADHA HPD OTC PAH
Sources

Drugs & Therapeutics for Phenylketonuria

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

(show top 50) (show all 61)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dopamine Approved Phase 4 51-61-6, 62-31-7 681
2
tannic acid Approved Phase 4 1401-55-4
3
Benzocaine Approved, Investigational Phase 4 94-09-7, 1994-09-7 2337
4
Melatonin Approved, Nutraceutical, Vet_approved Phase 4 73-31-4 896
5
Vitamin C Approved, Nutraceutical Phase 4 50-81-7 5785 54670067
6 Vitamins Phase 4
7 Pharmaceutical Solutions Phase 4
8 Anti-Infective Agents Phase 4
9 Antioxidants Phase 4
10
Procyanidin Phase 4 4852-22-6 147299
11 Anthocyanidin Phase 4
12 Antiprotozoal Agents Phase 4
13 Antiparasitic Agents Phase 4
14 Proanthocyanidin Phase 4
15 Protective Agents Phase 4
16
Serotonin Investigational, Nutraceutical Phase 4 50-67-9 5202
17 Dextrans Phase 3
18 Anticoagulants Phase 3
19 Plasma Substitutes Phase 3
20 Blood Substitutes Phase 3
21
Nitric Oxide Approved Phase 2 10102-43-9 145068
22
leucovorin Approved Phase 2 58-05-9 6006 143
23
Folic acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
24 Liver Extracts Phase 1, Phase 2
25 Trace Elements Phase 2
26 Nutrients Phase 2
27 Micronutrients Phase 2
28 Hematinics Phase 2
29 Vitamin B Complex Phase 2
30 Folate Phase 2
31 Vitamin B9 Phase 2
32
L-Alanine Nutraceutical Phase 2 56-41-7 5950
33
Histidine Investigational, Nutraceutical Phase 2 71-00-1 6274
34
Moxifloxacin Approved, Investigational Phase 1 354812-41-2, 151096-09-2 152946
35
Mannitol Approved, Investigational Phase 1 69-65-8 6251 453
36 Anti-Bacterial Agents Phase 1
37 Norgestimate, ethinyl estradiol drug combination Phase 1
38
Coal tar Approved 8007-45-2
39
Methylcobalamin Approved, Investigational 13422-55-4
40
Hydroxocobalamin Approved 13422-51-0 15589840 11953898
41
Cyanocobalamin Approved, Nutraceutical 68-19-9 44176380
42
Tyrosine Approved, Investigational, Nutraceutical 60-18-4 6057
43
arachidonic acid Experimental 506-32-1 444899
44
Cobalamin Experimental 13408-78-1 6857388
45 Whey Protein
46 Soy Bean
47 Fluorodeoxyglucose F18
48 Sunflower
49 Dermatologic Agents
50 Keratolytic Agents

Interventional clinical trials:

(show top 50) (show all 127)
# Name Status NCT ID Phase Drugs
1 ENDURE: A Phase IV, Prospective, Open-label, Uncontrolled, Multi-centre Cohort Trial to Assess the Responsiveness of Subjects With Phenylketonuria (PKU) to Treatment With Kuvan® 20 mg/kg/Day for 28 Days Completed NCT01082328 Phase 4 Kuvan®
2 Pilot Study to Evaluate Melatonin Secretion as a Marker of Decreased Serotonin in Individuals With PKU: Evaluation of the CNS Effects of Tetrahydrobiopterin Completed NCT01617070 Phase 4 Kuvan
3 Prospective Double-Blind Randomized Controlled Clinical Trial in the Gingivitis Prevention With an Oligomeric Proanthocyanidins Nutritional Supplement Completed NCT02515929 Phase 4
4 PEG-Electrolyte Solution (FORTRANS®) With Mentholyptus Drops (Halls®) Versus Reduced Volume Ascorbic Acid Supplemented PEG-Electrolyte (MoviPrep®) in Colonoscopy Preparation: A Randomised Controlled Study Completed NCT01788709 Phase 4
5 PICO: Phenylalanine and Its Impact on Cognition - Impact of Phenylalanine on Cognitive, Cerebral and Neurometabolic Parameters in Adult Patients With Phenylketonuria Recruiting NCT03788343 Phase 4 Placebo
6 The Effectiveness of High-Dose Synthetic BH4 (Saproterin Dihydrochloride or "Kuvan") in Amish PKU Patients Recruiting NCT02677870 Phase 4 saproterin dihydrochloride
7 A Phase 4 Open-Label, Single-Cohort Study of the Long-Term Neurocognitive Outcomes in 4 to 5 Year-Old Children With Phenylketonuria Treated With Sapropterin Dihydrochloride (Kuvan®) for 7 Years Active, not recruiting NCT01965912 Phase 4 Kuvan®
8 To Evaluate BH4 Responsiveness in PAH Deficiency PKU Patients Who Failed to Achieve 30% Blood Phe Reduction Within 24-hour BH4 Loading Test by Extending the Period of BH4 Response Test: A Pilot Study in Taiwan Not yet recruiting NCT04227080 Phase 4 BH4
9 A Phase 3, Randomized, Double-Blind, Placebo-Controlled 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
10 A Phase 3, Multicenter, Open-Label Extension Study of Phenoptin in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels Completed NCT00225615 Phase 3 sapropterin dihydrochloride
11 A Phase 3b, Multicenter, Open-Label Extension Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006 Completed NCT00332189 Phase 3 sapropterin dihydrochloride
12 A Phase IIIb, Multicentre, Open-Label, Randomized, Controlled Study of the Efficacy, Safety, and Population Pharmacokinetics of Sapropterin Dihydrochloride (Kuvan®) in Phenylketonuria (PKU) Patients <4 Years Old. Completed NCT01376908 Phase 3 Kuvan®
13 A Double-blind, Placebo-controlled, Randomized Study to Evaluate the Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Subjects With Phenylketonuria Completed NCT01114737 Phase 3 Sapropterin dihydrochloride;Placebo
14 A Phase III Non-comparative Open-label Clinical Study to Evaluate the Response to and Safety of Kuvan (Sapropterin Dihydrochloride) After 6 Weeks of Treatment in Patients of 4 to 18 Years of Age With Phenylketonuria Who Have Elevated Blood Phenylalanine Levels Completed NCT01732471 Phase 3 Kuvan®
15 A Phase 3, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Phenoptin to Increase Phenylalanine Tolerance in Phenylketonuric Children on a Phenylalanine-restricted Diet Completed NCT00272792 Phase 3 Sapropterin Dihydrochloride;Placebo
16 A Four-Part, Phase 3, Randomized, Double-Blind, Placebo- Controlled, Four-Arm, Discontinuation Study to Evaluate the Efficacy and Safety of Subcutaneous Injections of BMN 165 Self-Administered by Adults With Phenylketonuria (PKU) Completed NCT01889862 Phase 3 BMN165 20mg/day;BMN165 40mg/day;Placebo
17 A Phase 3b Open-Label Study to Evaluate the Effect of Kuvan® on Neurocognitive Function, Maintenance of Blood Phenylalanine Concentrations, Safety, and Population Pharmacokinetics in Young Children With Phenylketonuria Completed NCT00838435 Phase 3 sapropterin dihydrochloride
18 A Phase 3, Open-Label, Randomized, Multi-Center Study to Assess the Safety & Tolerability of an Induction, Titration, and Maintenance Dose Regimen of BMN 165 Self Administered by Adults With PKU Not Previously Treated With BMN 165 Completed NCT01819727 Phase 3 BMN 165
19 An Open-label Extension Study to Evaluate the Safety and Efficacy of Subcutaneous Injections of Pegvaliase (> 40 mg/Day Dose) in Adults With Phenylketonuria Active, not recruiting NCT03694353 Phase 3 Pegvaliase
20 Double-Blind, Placebo Controlled, Multicentre Study With an Open Label Extension to Evaluate the Efficacy and Safety of Tetrahydrobiopterin (BH4) in Children and Adolescents With Hyperphenylalaninemia Caused by Phenylalanine Hydroxylase Deficiency Terminated NCT00432822 Phase 2, Phase 3 tetrahydrobiopterin (BH4)
21 An Open-Label, Pilot Study of a Red Blood Cell Precursor Formulation to Determine Increased Production in Subjects With Mild to Moderate Anemia Withdrawn NCT01701531 Phase 2, Phase 3 RBCPF
22 Trial of Kuvanâ„¢ (Sapropterin) Treatment in Patients With Lesch Nyhan Disease Withdrawn NCT00935753 Phase 2, Phase 3 sapropterin
23 Study of the Response of Tetrahydrobiopterin on S-Phenylalanine in Patients With PKU Housing the Y414C Mutation Completed NCT00260000 Phase 2 5,6,7,8-tetrahydrobiopterin
24 A Phase 2, Multicenter, Open-Label Study to Evaluate the Response to and Safety of an 8-Day Course of Phenoptinâ„¢ Treatment in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels Completed NCT00104260 Phase 2 sapropterin dihydrochloride
25 Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response Completed NCT00841100 Phase 2 Kuvan
26 A Phase 1/2a, First-in-human, Oral Single and Multiple Dose-Escalation, Randomized, Double-blinded, Placebo-controlled Study of SYNB1618 in Healthy Adult Volunteers and Adult Subjects With Phenylketonuria to Evaluate Safety, Tolerability, Kinetics, and Pharmacodynamics Completed NCT03516487 Phase 1, Phase 2 SYNB1618;Placebo
27 A Phase 2, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Subcutaneous Dose Levels of rAvPAL-PEG Administered Daily in Subjects With Phenylketonuria Completed NCT01212744 Phase 2 rAvPAL-PEG
28 A Phase II, Multi-center, Open-label, Dose-finding Study to Evaluate Safety, Efficacy and Tolerability of Subcutaneously (SC) Administered rAvPAL-PEG in Patients With PKU for 24 Weeks Completed NCT01560286 Phase 2
29 Long-term Extension of a Phase 2, Open-Label Dose-Finding Study to Evaluate the Safety, Efficacy, and Tolerability of Multiple Subcutaneous Doses of rAvPAL-PEG in Subjects With PKU Completed NCT00924703 Phase 2 rAvPAL-PEG
30 Phase 2, Multicenter, Open Label Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to Primary BH4 Deficiency Completed NCT00355264 Phase 2 Phenoptin
31 Phase 2, Open-Label Dose-Finding Study to Evaluate the Safety, Efficacy, and Tolerability of Multiple Subcutaneous (SC) Doses of rAvPAL-PEG in Subjects With PKU Completed NCT00925054 Phase 2 rAvPAL-PEG 0.001 mg/kg;rAvPAL-PEG 0.003 mg/kg;rAvPAL-PEG 0.01 mg/kg;rAvPAL-PEG 0.03 mg/kg;rAvPAL-PEG 0.1 mg/kg
32 A Phase 1/2 Open-Label, Randomized, Concurrently-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of HMI-102 in Adult PKU Subjects With PAH Deficiency Recruiting NCT03952156 Phase 1, Phase 2
33 Hepatocyte Transplantation for Phenylketonuria Recruiting NCT01465100 Phase 1, Phase 2 Immunosuppression
34 A Phase 1/2, Open-Label, Randomized Parallel Arm, Intra-patient Dose Escalation Study to Evaluate Safety, PK and Preliminary Efficacy of CNSA-001 in Primary Tetrahydrobiopterin Deficient Patients With Hyperphenylalaninemia Recruiting NCT03519711 Phase 1, Phase 2 CNSA-001
35 Neurovascular Regulation During Exercise in Humans With Chronic Kidney Disease Suspended NCT02947750 Phase 2 6R-BH4
36 A Multicenter, Double-Blind, Placebo-Controlled, Randomized, 2-Arm Phase IIa Pilot Trial Assessing the Effect of Sapropterin on Cognitive Abilities in Young Adults With Phenylketonuria Terminated NCT01977820 Phase 2 Sapropterin;Placebo
37 The Ability of Kuvan® (Sapropterin Dihydrochloride) to Prevent Meal-induced Lipid Peroxidation and Endothelial Dysfunction in Patients With Phenylketonuria: a Pilot Study Terminated NCT01395394 Phase 2 Kuvan
38 Response to Phenylketonuria to Tetrahydrobiopterin (BH4) Unknown status NCT00244218 Phase 1 tetrahydrobiopterin (BH4)
39 A Phase 1, Randomized, Placebo- and Active-controlled Crossover Study to Evaluate the Effects of Sapropterin Dihydrochloride Oral Administration on QTc Intervals in Healthy Adult Subjects Completed NCT00789568 Phase 1 sapropterin dihydrochloride;Moxifloxacin
40 A Phase I, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single, Subcutaneous Doses of rAvPAL-PEG in Subjects With Phenylketonuria Completed NCT00634660 Phase 1 rAvPAL-PEG
41 A Phase 1, Multi-center, Randomized, Double-blind, Placebo-controlled, Cross-over Study to Evaluate the Pharmacodynamics, Safety, Tolerability and Pharmacokinetics of a Single Oral Dose of CDX-6114 in Patients With Phenylketonuria (PKU). Recruiting NCT04085666 Phase 1 CDX 6114
42 A Phase 1b Open-Label Single Dose Safety, Tolerability, and Pharmacokinetics Study of RTX-134 in Adults With Phenylketonuria Active, not recruiting NCT04110496 Phase 1 RTX-134
43 A Phase 1, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of CDX 6114 After Multiple Ascending Oral Dose Administration to Patients With Phenylketonuria (PKU). Not yet recruiting NCT04256655 Phase 1 cohort 1 0.225g;Cohort 2 0.75g;Cohort 3 2.25 g
44 Role of Nitric Oxide Coupling in Muscle Dysfunction With COPD Not yet recruiting NCT04014712 Phase 1 Tetrahydrobiopterin;Placebo oral tablet
45 - Contribution of Diet Induced Thermogenesis (DIT) and Fat Oxidation to Body Fatness and Body Composition of Patients With Phenylketonuria - Contribution of Physical Activity Energy Expenditure and Energy Intake to Body Fatness and Body Composition of Patients With Phenylketonuria Unknown status NCT03309345
46 Neonatal Hearing Screening at Neonatal Intensive Care Unit of Assiut University Hospital Unknown status NCT03251638
47 Gluten Dietary Intervention for Autistic Symptoms in Children With Autism Spectrum Disorders - Randomized Open Trial Unknown status NCT02280746
48 Sapropterin Expanded Access Program Approved for marketing NCT00484991 Sapropterin dihydrochloride
49 Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia Completed NCT01869972
50 Effects of Maternal Phenylketonuria (PKU) on Pregnancy Outcome Completed NCT00065299

Search NIH Clinical Center for Phenylketonuria

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Read about Phenylketonuria cell therapies at LifeMap Discovery.
Stem-cell-based therapeutic approaches for Phenylketonuria:
Hepatocyte transplantation for treatment of liver disorders
Embryonic/Adult Cultured Cells Related to Phenylketonuria:
Hepatocytes PMIDs: 12777539 22167636 22789058 9580649 15239608

Cochrane evidence based reviews: phenylketonurias

Sources

Genetic Tests for Phenylketonuria

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Genetic tests related to Phenylketonuria:

# Genetic test Affiliating Genes
1 Phenylketonuria 29 PAH
2 Maternal Phenylketonuria 29
Sources

Anatomical Context for Phenylketonuria

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MalaCards organs/tissues related to Phenylketonuria:

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

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

Publications for Phenylketonuria

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Articles related to Phenylketonuria:

(show top 50) (show all 5732)
# Title Authors PMID Year
1
Phenylalanine hydroxylase deficiency: diagnosis and management guideline. 56 6 24 61
24385074 2014
2
Molecular structure and polymorphic map of the human phenylalanine hydroxylase gene. 6 56 61 24
3008810 1986
3
Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability. 56 6 61
18538294 2008
4
Phenylalanine hydroxylase deficiency exhibits mutation heterogeneity in two large old order Amish settlements. 6 56 61
17630668 2007
5
Molecular and phenotypic characteristics of patients with phenylketonuria in Serbia and Montenegro. 56 6 61
16879198 2006
6
A molecular survey of phenylketonuria in Iceland: identification of a founding mutation and evidence of predominant Norse settlement. 56 6 61
9450182 1997
7
Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria. 6 61 56
8098245 1993
8
Illegitimate transcription of phenylalanine hydroxylase for detection of mutations in patients with phenylketonuria. 61 6 56
1301202 1992
9
Silent mutations in the phenylalanine hydroxylase gene as an aid to the diagnosis of phenylketonuria. 61 56 6
1682495 1991
10
Mutation detection in phenylketonuria by using chemical cleavage of mismatch: importance of using probes from both normal and patient samples. 6 56 61
2063869 1991
11
Maternal phenylketonuria syndrome in cousins caused by mild, unrecognized phenylketonuria in their mothers homozygous for the phenylalanine hydroxylase Arg-261-Gln mutation. 61 6 56
1915502 1991
12
Phenylketonuria in U.S. blacks: molecular analysis of the phenylalanine hydroxylase gene. 61 56 6
2014802 1991
13
CpG dinucleotides are mutation hot spots in phenylketonuria. 6 56 61
2574153 1989
14
Phenylketonuria Scientific Review Conference: state of the science and future research needs. 61 6 24
24667081 2014
15
Psychiatric symptoms and disorders in phenylketonuria. 24 56 61
20123472 2010
16
Short-term dietary interventions in children and adolescents with treated phenylketonuria: effects on neuropsychological outcome of a well-controlled population. 61 56 24
12555935 2002
17
Individual blood-brain barrier phenylalanine transport in siblings with classical phenylketonuria. 61 24 56
12555936 2002
18
Phenylketonuria in adulthood: a collaborative study. 61 56 24
12408183 2002
19
Recurrent mutation, gene conversion, or recombination at the human phenylalanine hydroxylase locus: evidence in French-Canadians and a catalog of mutations. 6 56
1971147 1990
20
Molecular genetics of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. 56 54 61
17935162 2008
21
Tetrahydrobiopterin responsiveness in phenylketonuria. Two new cases and a review of molecular genetic findings. 56 54 61
11999982 2002
22
A silent mutation induces exon skipping in the phenylalanine hydroxylase gene in phenylketonuria. 6 61 54
11214902 2001
23
Characterization of phenylketonuria missense substitutions, distant from the phenylalanine hydroxylase active site, illustrates a paradigm for mechanism and potential modulation of phenotype. 61 54 56
10720436 2000
24
Gypsy phenylketonuria: a point mutation of the phenylalanine hydroxylase gene in Gypsy families from Slovakia. 61 54 6
8116675 1994
25
A frameshift mutation in exon 2 of the phenylalanine hydroxylase gene linked to RFLP haplotype 1. 54 6 61
1682235 1991
26
The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations. 56 61 54
1679029 1991
27
The identification of two mis-sense mutations at the PAH gene locus in a Turkish patient with phenylketonuria. 54 61 6
1679030 1991
28
Missense mutations prevalent in Orientals with phenylketonuria: molecular characterization and clinical implications. 61 54 6
2071149 1991
29
A 3-base pair in-frame deletion of the phenylalanine hydroxylase gene results in a kinetic variant of phenylketonuria. 61 54 6
1709636 1991
30
Founder effect of a prevalent phenylketonuria mutation in the Oriental population. 6 61 54
2006152 1991
31
Two mutations within the coding sequence of the phenylalanine hydroxylase gene. 61 6 54
1975559 1990
32
Prenatal detection of an Arg----Ter mutation at codon 111 of the PAH gene using DNA amplification. 54 61 6
1975096 1990
33
Molecular genetics of PKU in eastern Europe: a nonsense mutation associated with haplotype 4 of the phenylalanine hydroxylase gene. 6 61 54
2309142 1990
34
Long-term comparative effectiveness of pegvaliase versus standard of care comparators in adults with phenylketonuria. 56 61
31439512 2019
35
Vitamin and mineral status in patients with hyperphenylalaninemia. 61 56
26123187 2015
36
Recommendations for the nutrition management of phenylalanine hydroxylase deficiency. 61 56
24385075 2014
37
Long-term follow-up and outcome of phenylketonuria patients on sapropterin: a retrospective study. 61 56
23690520 2013
38
Clinical utility gene card for: Phenylketonuria. 61 6
21915151 2012
39
Phenylketonuria. 61 56
20971365 2010
40
Pahenu1 is a mouse model for tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency and promotes analysis of the pharmacological chaperone mechanism in vivo. 61 56
20179079 2010
41
Animal models of brain dysfunction in phenylketonuria. 61 56
20123463 2010
42
Psychosocial aspects of PKU: hidden disabilities--a review. 56 61
20123473 2010
43
Predicted effects of missense mutations on native-state stability account for phenotypic outcome in phenylketonuria, a paradigm of misfolding diseases. 61 56
17924342 2007
44
The PAH gene, phenylketonuria, and a paradigm shift. 61 56
17443661 2007
45
Efficiency of long-term tetrahydrobiopterin monotherapy in phenylketonuria. 61 56
15303001 2004
46
Biopterin responsive phenylalanine hydroxylase deficiency. 61 56
14726806 2004
47
Cerebral energy metabolism in phenylketonuria: findings by quantitative In vivo 31P MR spectroscopy. 56 61
12612190 2003
48
Genetic diversity within the R408W phenylketonuria mutation lineages in Europe. 61 6
12655548 2003
49
Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. 56 61
12501224 2002
50
The impact of the control of serum phenylalanine levels on osteopenia in patients with phenylketonuria. 61 56
12536994 2002
Sources

Variations for Phenylketonuria

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ClinVar genetic disease variations for Phenylketonuria:

6 (show top 50) (show all 592) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PAH NC_000012.11:g.(?_103248894)_(103249130_?)deldeletion Pathogenic 458077 12:103248894-103249130
2 PAH NM_000277.3(PAH):c.865G>A (p.Gly289Arg)SNV Pathogenic 458082 rs199475693 12:103245512-103245512 12:102851734-102851734
3 PAH NM_000277.3(PAH):c.553_706+647deldeletion Pathogenic 458079 rs1555204616 12:103248267-103249067 12:102854489-102855289
4 PAH NC_000012.12:g.(?_102854491)_(102855289_?)deldeletion Pathogenic 527864 12:103248269-103249067 12:102854491-102855289
5 PAH NC_000012.12:g.(?_102866576)_(102866683_?)deldeletion Pathogenic 527865 12:103260354-103260461 12:102866576-102866683
6 PAH NM_000277.3(PAH):c.707-12_711deldeletion Pathogenic 527863 rs1555204492 12:103246724-103246740 12:102852946-102852962
7 PAH NM_000277.3(PAH):c.169-2A>GSNV Pathogenic 555212 rs1226613045 12:103288698-103288698 12:102894920-102894920
8 PAH NM_000277.3(PAH):c.800A>G (p.Gln267Arg)SNV Pathogenic 556296 rs778154939 12:103246635-103246635 12:102852857-102852857
9 PAH NM_000277.3(PAH):c.618C>A (p.Tyr206Ter)SNV Pathogenic 556660 rs62517201 12:103249002-103249002 12:102855224-102855224
10 PAH NM_000277.3(PAH):c.127G>T (p.Glu43Ter)SNV Pathogenic 557124 rs1555209575 12:103306610-103306610 12:102912832-102912832
11 PAH NC_000012.12:g.(?_102894715)_(102894938_?)deldeletion Pathogenic 584242 12:103288493-103288716 12:102894715-102894938
12 PAH NM_000277.3(PAH):c.686dup (p.Asp229fs)duplication Pathogenic 576828 rs1565848110 12:103248933-103248934 12:102855155-102855156
13 PAH NM_000277.3(PAH):c.1153del (p.Leu385fs)deletion Pathogenic 580754 rs1565842203 12:103237470-103237470 12:102843692-102843692
14 PAH NM_000277.3(PAH):c.470_471delinsAC (p.Arg157Asn)indel Pathogenic 590772 rs1565853495 12:103260412-103260413 12:102866634-102866635
15 PAH NM_000277.3(PAH):c.788T>C (p.Phe263Ser)SNV Pathogenic 619150 rs1565846863 12:103246647-103246647 12:102852869-102852869
16 PAH NM_000277.3(PAH):c.697T>A (p.Phe233Ile)SNV Pathogenic 619163 rs1565848061 12:103248923-103248923 12:102855145-102855145
17 PAH NM_000277.3(PAH):c.1109A>G (p.Glu370Gly)SNV Pathogenic 625290 12:103237514-103237514 12:102843736-102843736
18 PAH NM_000277.3(PAH):c.1102G>A (p.Glu368Lys)SNV Pathogenic 625289 12:103237521-103237521 12:102843743-102843743
19 PAH NM_000277.3(PAH):c.590T>A (p.Leu197Ter)SNV Pathogenic 625288 12:103249030-103249030 12:102855252-102855252
20 PAH NM_000277.3(PAH):c.32T>A (p.Leu11Ter)SNV Pathogenic 625287 12:103310877-103310877 12:102917099-102917099
21 PAH NM_000277.3(PAH):c.1200-2A>CSNV Pathogenic 625286 12:103234295-103234295 12:102840517-102840517
22 PAH NM_000277.3(PAH):c.875C>T (p.Pro292Leu)SNV Pathogenic 626282 rs1200240274 12:103245502-103245502 12:102851724-102851724
23 PAH NM_000277.3(PAH):c.346_347del (p.Asp116fs)deletion Pathogenic 635217 12:103288518-103288519 12:102894740-102894741
24 PAH NM_000277.3(PAH):c.1316-1G>ASNV Pathogenic 635216 12:103232997-103232997 12:102839219-102839219
25 PAH NM_000277.3(PAH):c.(?_169)_352+?deldeletion Pathogenic 620579 12:102894735-102894918
26 PAH NM_000277.3(PAH):c.799C>T (p.Gln267Ter)SNV Pathogenic 665198 12:103246636-103246636 12:102852858-102852858
27 PAH NM_000277.3(PAH):c.516G>T (p.Gln172His)SNV Pathogenic 664621 12:103249104-103249104 12:102855326-102855326
28 PAH NC_000012.12:g.(?_102855126)_(102855342_?)deldeletion Pathogenic 642631 12:103248904-103249120 12:102855126-102855342
29 PAH NC_000012.12:g.(?_102917061)_(102917140_?)deldeletion Pathogenic 646971 12:103310839-103310918 12:102917061-102917140
30 PAH NM_000277.3(PAH):c.1098_1099insTCTTATCAGAGAAGCCAAAGCTTCTCCCC (p.Leu367fs)insertion Pathogenic 802885 12:103237524-103237525 12:102843746-102843747
31 PAH NM_000277.3(PAH):c.902A>C (p.Gln301Pro)SNV Pathogenic 805825 12:103245475-103245475 12:102851697-102851697
32 PAH NM_000277.3(PAH):c.901C>T (p.Gln301Ter)SNV Pathogenic 805824 12:103245476-103245476 12:102851698-102851698
33 PAH NM_000277.3(PAH):c.266_267insG (p.Ala90fs)insertion Pathogenic 805816 12:103288598-103288599 12:102894820-102894821
34 PAH NM_000277.3(PAH):c.206dup (p.Ser70fs)duplication Pathogenic 805815 12:103288658-103288659 12:102894880-102894881
35 PAH NM_000277.3(PAH):c.190_194del (p.Thr63_His64insTer)deletion Pathogenic 805814 12:103288671-103288675 12:102894893-102894897
36 PAH NM_000277.3(PAH):c.189_190dup (p.His64fs)duplication Pathogenic 805813 12:103288674-103288675 12:102894896-102894897
37 PAH NM_000277.3(PAH):c.184_185insCTGA (p.Leu62fs)insertion Pathogenic 805811 12:103288680-103288681 12:102894902-102894903
38 PAH NM_000277.3(PAH):c.184del (p.Asn61_Leu62insTer)deletion Pathogenic 805812 12:103288681-103288681 12:102894903-102894903
39 PAH NM_000277.3(PAH):c.169_170GA[1] (p.Glu57_Asn58insTer)short repeat Pathogenic 805810 12:103288693-103288694 12:102894915-102894916
40 PAH NM_000277.3(PAH):c.168+2T>CSNV Pathogenic 805828 12:103306567-103306567 12:102912789-102912789
41 PAH NM_000277.3(PAH):c.239dup (p.Thr81fs)duplication Pathogenic 802887 12:103288625-103288626 12:102894847-102894848
42 PAH NM_000277.3(PAH):c.707-2deldeletion Pathogenic 805819 12:103246730-103246730 12:102852952-102852952
43 PAH NM_000277.3(PAH):c.43_44insAG (p.Leu15fs)insertion Pathogenic 805801 12:103310865-103310866 12:102917087-102917088
44 PAH NM_000277.3(PAH):c.30dup (p.Arg13fs)duplication Pathogenic 805800 12:103310878-103310879 12:102917100-102917101
45 PAH NM_000277.3(PAH):c.13del (p.Val5fs)deletion Pathogenic 805799 12:103310896-103310896 12:102917118-102917118
46 PAH NC_000012.12:g.(?_102866586)_(102866673_?)deldeletion Pathogenic 832845 12:103260364-103260451
47 PAH NC_000012.12:g.(?_102894725)_(102894931_?)deldeletion Pathogenic 831713 12:103288503-103288709
48 PAH NM_000277.3(PAH):c.48dup (p.Asp17Ter)duplication Pathogenic 805804 12:103310860-103310861 12:102917082-102917083
49 PAH NM_000277.3(PAH):c.47_48insCT (p.Asp17fs)insertion Pathogenic 805802 12:103310861-103310862 12:102917083-102917084
50 PAH NM_000277.3(PAH):c.1174T>A (p.Phe392Ile)SNV Pathogenic 853581 12:103237449-103237449 12:102843671-102843671

UniProtKB/Swiss-Prot genetic disease variations for Phenylketonuria:

73 (show top 50) (show all 206)
# Symbol AA change Variation ID SNP ID
1 PAH p.Ser16Pro VAR_000869 rs62642946
2 PAH p.Phe39Leu VAR_000870 rs62642926
3 PAH p.Ser40Leu VAR_000872 rs62642938
4 PAH p.Leu41Phe VAR_000873 rs62642928
5 PAH p.Lys42Ile VAR_000874 rs62635346
6 PAH p.Gly46Ser VAR_000875 rs74603784
7 PAH p.Ala47Val VAR_000876 rs118203925
8 PAH p.Leu48Ser VAR_000877 rs5030841
9 PAH p.Arg53His VAR_000878 rs118092776
10 PAH p.Phe55Leu VAR_000879 rs199475598
11 PAH p.Glu56Asp VAR_000880 rs199475567
12 PAH p.Ile65Asn VAR_000882 rs75193786
13 PAH p.Ile65Thr VAR_000883 rs75193786
14 PAH p.Ser67Pro VAR_000884 rs5030842
15 PAH p.Arg68Ser VAR_000885 rs76394784
16 PAH p.Glu76Ala VAR_000886 rs62507347
17 PAH p.Asp84Tyr VAR_000887 rs62514902
18 PAH p.Ser87Arg VAR_000888 rs62516151
19 PAH p.Thr92Ile VAR_000889 rs62514903
20 PAH p.Leu98Ser VAR_000891 rs62517167
21 PAH p.Ala104Asp VAR_000892 rs62642929
22 PAH p.Thr124Ile VAR_000893 rs199475571
23 PAH p.Asp129Tyr VAR_000894 rs199475606
24 PAH p.Asp143Gly VAR_000895 rs199475572
25 PAH p.His146Tyr VAR_000896 rs199475599
26 PAH p.Gly148Ser VAR_000897 rs80297647
27 PAH p.Asp151His VAR_000898 rs199475597
28 PAH p.Tyr154Asn VAR_000899 rs199475587
29 PAH p.Arg157Asn VAR_000900
30 PAH p.Arg158Gln VAR_000901 rs5030843
31 PAH p.Arg158Trp VAR_000902 rs75166491
32 PAH p.Gln160Pro VAR_000903 rs199475601
33 PAH p.Phe161Ser VAR_000904 rs79635844
34 PAH p.Ile164Thr VAR_000905 rs199475595
35 PAH p.Asn167Ile VAR_000906 rs77554925
36 PAH p.His170Arg VAR_000907 rs199475573
37 PAH p.Gly171Ala VAR_000908 rs199475596
38 PAH p.Gly171Arg VAR_000909 rs199475613
39 PAH p.Pro173Thr VAR_000910 rs199475574
40 PAH p.Ile174Thr VAR_000911 rs138809906
41 PAH p.Pro175Ala VAR_000912 rs199475604
42 PAH p.Arg176Leu VAR_000913 rs74486803
43 PAH p.Arg176Pro VAR_000914 rs74486803
44 PAH p.Val177Leu VAR_000915 rs199475602
45 PAH p.Glu178Gly VAR_000916 rs77958223
46 PAH p.Val190Ala VAR_000917 rs62514919
47 PAH p.Leu194Pro VAR_000918 rs5030844
48 PAH p.His201Arg VAR_000922 rs62517180
49 PAH p.His201Tyr VAR_000923 rs62517205
50 PAH p.Tyr204Cys VAR_000924 rs62514927

Sources

Expression for Phenylketonuria

About this section
Search GEO for disease gene expression data for Phenylketonuria.
Sources

Pathways for Phenylketonuria

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Pathways related to Phenylketonuria according to KEGG:

36
# Name Kegg Source Accession
1 Phenylalanine, tyrosine and tryptophan biosynthesis hsa00400
2 Folate biosynthesis hsa00790

Pathways related to Phenylketonuria according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Metabolism 65
Show member pathways
 13.56 TTR TPH1 TH SLC7A5 QDPR PTS
2
Carbon metabolism 36
Show member pathways
 12.04 PAH OTC MTHFR HADHA G6PD
3
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways 1
11.86 TPH1 TH PAH HADHA ACADM
4
Amino Acid metabolism 1
11.66 TPH1 TH OTC ACADM
5
Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism 65
Show member pathways
 11.64 SLC7A5 QDPR PCBD1 PAH HPD
6
Tyrosine metabolism 36
Show member pathways
 11.51 TH PAH HPD
7
FOXA2 and FOXA3 transcription factor networks 1
11.25 TTR ALB ACADM
8
Biogenic Amine Synthesis 1
Show member pathways
 10.89 TPH1 TH PAH
9
Folate biosynthesis 36
Show member pathways
 10.63 TPH1 TH QDPR PTS PCBD1 PAH
10
Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA 65
Show member pathways
 10.48 HADHA ACADM
Sources

GO Terms for Phenylketonuria

About this section

Cellular components related to Phenylketonuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.4 TPH1 TH SLC7A5 QDPR PTS PCBD1

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

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 response to drug GO:0042493 9.85 TH OTC MTHFR HADHA BGLAP
2 metabolic process GO:0008152 9.8 PAH MTHFR HADHA GCH1
3 response to ethanol GO:0045471 9.73 TH G6PD BGLAP
4 liver development GO:0001889 9.71 QDPR OTC ACADM
5 oxidation-reduction process GO:0055114 9.65 TPH1 TH QDPR PCBD1 PAH MTHFR
6 response to nutrient levels GO:0031667 9.62 TH OTC GHRL BGLAP
7 cellular amino acid metabolic process GO:0006520 9.61 QDPR PTS OTC
8 response to zinc ion GO:0010043 9.58 TH OTC BGLAP
9 L-phenylalanine catabolic process GO:0006559 9.56 QDPR PCBD1 PAH HPD
10 neurotransmitter biosynthetic process GO:0042136 9.55 TH PAH
11 cofactor metabolic process GO:0051186 9.52 PTS GCH1
12 dopamine biosynthetic process GO:0042416 9.51 TH GCH1
13 catecholamine biosynthetic process GO:0042423 9.48 TH PAH
14 aromatic amino acid family metabolic process GO:0009072 9.46 TPH1 TH PAH HPD
15 dihydrobiopterin metabolic process GO:0051066 9.37 QDPR GCH1
16 tetrahydrobiopterin biosynthetic process GO:0006729 8.92 QDPR PTS PCBD1 GCH1

Molecular functions related to Phenylketonuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 identical protein binding GO:0042802 9.85 TTR QDPR PTS PCBD1 OTC GCH1
2 catalytic activity GO:0003824 9.8 PAH MTHFR HADHA GCH1 ADSL
3 lyase activity GO:0016829 9.62 PTS PCBD1 HADHA ADSL
4 monooxygenase activity GO:0004497 9.54 TPH1 TH PAH
5 oxidoreductase activity GO:0016491 9.28 TPH1 TH QDPR PAH MTHFR HPD
6 phenylalanine 4-monooxygenase activity GO:0004505 9.26 PCBD1 PAH
7 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen GO:0016714 9.13 TPH1 TH PAH
Sources

Sources for Phenylketonuria

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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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