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PKU
MCID: PHN003
MIFTS: 76

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

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MalaCards integrated aliases for Phenylketonuria:

Name: Phenylketonuria 57 12 73 20 43 58 72 36 29 13 6 42 15 37 39
Phenylalanine Hydroxylase Deficiency 57 73 25 20 43 58
Pku 57 12 20 43 58 72
Pah Deficiency 57 25 43 58
Maternal Phenylketonuria 12 58 29
Phenylketonurias 54 44 70
Folling Disease 57 20 43
Hyperphenylalaninemia, Non-Pku Mild 57 6
Oligophrenia Phenylpyruvica 57 20
Phenylketonuria, Maternal 44 70
Variant Phenylketonuria 20 58
Mild Phenylketonuria 20 58
Folling's Disease 12 43
Phenylalaninemia 12 73
Variant Pku 20 58
Mild Pku 20 58
Mpku 20 58
Deficiency Disease, Phenylalanine Hydroxylase 43
Phenylalanine Hydroxylase Deficiency Disease 43
Non-Phenylketonuria Hyperphenylalaninemia 72
Hyperphenylalaninemic Embryopathy 58
Maternal Hyperphenylalaninemia 58
Phenylketonuric Embryopathy 58
Classical Phenylketonuria 70
Phenylketonuria Maternal 54
Hyperphenylalaninaemia 70
Hyperphenylalaninemia 72
Maternal Pku 58
Non-Pku Hpa 72
Hpa 72

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®:

57 (Updated 20-May-2021)
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: 33
Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism
Developmental anomalies during embryogenesis
Teratologic disorders


Sources

Summaries for Phenylketonuria

About this section
MedlinePlus Genetics : 43 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, tremor and dry skin. 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 heart, 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.

GARD : 20 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® : 57 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) (Updated 20-May-2021)

MedlinePlus : 42 Phenylketonuria (PKU) is a type of amino acid metabolism disorder. It is inherited. If you have it, your body can't process phenylalanine (Phe). Phe is an amino acid, a building block of proteins. It 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 : 72 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 : 73 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 609)
# Related Disease Score Top Affiliating Genes
1 classic phenylketonuria 32.8 QDPR PTS PAH
2 hyperphenylalaninemia, bh4-deficient, b 32.4 TH QDPR PTS GCH1
3 segawa syndrome, autosomal recessive 32.0 TH GCH1
4 dystonia, dopa-responsive, due to sepiapterin reductase deficiency 31.9 QDPR PCBD1 GCH1
5 hyperphenylalaninemia, bh4-deficient, a 31.8 QDPR PTS PCBD1 PAH GCH1
6 hyperphenylalaninemia 31.7 TPH1 TH QDPR PTS PCBD1 PAH
7 amino acid metabolic disorder 31.2 PAH OTC MTHFR HPD HGD BTD
8 mild hyperphenylalaninemia 31.1 QDPR PTS PCBD1 PAH
9 congenital hypothyroidism 30.8 G6PD BTD ALB ACADM
10 galactosemia i 30.6 PAH G6PD BTD ACADM
11 tetrahydrobiopterin deficiency 30.5 TH QDPR PTS PCBD1 PAH GCH1
12 tyrosinemia 30.4 QDPR PTS PAH HPD HGD BTD
13 keratomalacia 30.3 TTR QDPR
14 sleep disorder 30.3 TH GCH1 ALB
15 dystonia 30.2 TPH1 TH QDPR PTS PCBD1 PAH
16 psychotic disorder 30.1 TPH1 TH PAH MTHFR MAOB
17 personality disorder 30.1 TPH1 TH MAOB
18 alkaptonuria 30.1 PAH HPD HGD ADSL
19 nutritional deficiency disease 30.1 TTR MTHFR ALB
20 tyrosinemia, type i 30.0 OTC HPD HGD
21 west syndrome 30.0 TPH1 TH MTHFR BTD
22 enteropathica 30.0 OTC ALB
23 homocystinuria 29.9 OTC MTHFR HADHA ALB ADSL
24 pentosuria 29.7 PCBD1 HGD
25 abdominal obesity-metabolic syndrome 1 29.6 PTS PAH OTC HGD HADHA BTD
26 glycogen storage disease 29.6 OTC MTHFR BTD ALB
27 autism 29.5 TPH1 TH PAH MTHFR MAOB ADSL
28 acyl-coa dehydrogenase, medium-chain, deficiency of 29.5 PAH HADHA BTD ACADM
29 biotinidase deficiency 29.5 HADHA BTD ADSL
30 parkinson disease, late-onset 29.5 TTR TPH1 TH QDPR PAH MAOB
31 disease of mental health 29.4 TTR TPH1 TH PAH MTHFR MAOB
32 maple syrup urine disease 29.3 SLC7A5 QDPR PAH OTC HADHA BTD
33 methylmalonic acidemia 29.2 PAH OTC MTHFR HADHA ACADM
34 hyperphenylalaninemia, bh4-deficient, d 11.8
35 hyperphenylalaninemia, mild, non-bh4-deficient 11.5
36 maternal hyperphenylalaninemia 11.4
37 gtp cyclohydrolase 1-deficient dopa-responsive dystonia 11.2
38 hyperphenylalaninemia, bh4-deficient, c 11.2
39 tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria 11.1
40 microcephaly 11.1
41 dystonia, dopa-responsive 11.1
42 hpa i recognition polymorphism, beta-globin-related 11.0
43 spasticity 10.9
44 glycine encephalopathy 10.9
45 tyrosine-oxidase temporary deficiency 10.9
46 thrombocytopenia 10.8
47 fetal and neonatal alloimmune thrombocytopenia 10.6
48 purpura 10.6
49 inherited metabolic disorder 10.6
50 autosomal recessive disease 10.5

Graphical network of the top 20 diseases related to Phenylketonuria:



Diseases related to Phenylketonuria
Sources

Symptoms & Phenotypes for Phenylketonuria

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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 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
11 wide nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0000431
12 anteverted nares 58 31 occasional (7.5%) Occasional (29-5%) HP:0000463
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 seizures 58 Occasional (29-5%)
36 hyperreflexia 31 HP:0001347
37 depressivity 31 HP:0000716
38 cerebral calcification 31 HP:0002514
39 cataract 31 HP:0000518
40 malformation of the heart and great vessels 58 Occasional (29-5%)
41 dry skin 31 HP:0000958
42 attention deficit hyperactivity disorder 31 HP:0007018
43 anxiety 31 HP:0000739
44 irritability 31 HP:0000737
45 blue irides 31 HP:0000635
46 obsessive-compulsive behavior 31 HP:0000722
47 generalized hypopigmentation 31 HP:0007513
48 eczema 31 HP:0000964
49 psychosis 31 HP:0000709
50 abnormal heart morphology 58 Very frequent (99-80%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
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 (Updated 20-May-2021)

UMLS symptoms related to Phenylketonuria:


seizures; tremor; dry skin; 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 9.66 ADSL
2 Decreased viability GR00249-S 9.66 ACADM ALB G6PD MAOB PCBD1 SLC7A5
3 Decreased viability GR00381-A-1 9.66 GCH1 HGD
4 Decreased viability GR00386-A-1 9.66 ACADM ALB G6PD HADHA HPD MTHFR
5 Decreased viability GR00402-S-2 9.66 ACADM G6PD SLC7A5

MGI Mouse Phenotypes related to Phenylketonuria:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.35 ACADM ALB BTD G6PD GCH1 HADHA
2 cardiovascular system MP:0005385 10.1 ACADM ADSL ALB G6PD GCH1 HADHA
3 integument MP:0010771 9.97 ACADM BTD MTHFR OTC PAH PCBD1
4 mortality/aging MP:0010768 9.97 ACADM ADSL ALB G6PD GCH1 HADHA
5 liver/biliary system MP:0005370 9.86 ACADM ALB GCH1 HADHA HGD MTHFR
6 renal/urinary system MP:0005367 9.36 ALB BTD HADHA HGD HPD MAOB
7 pigmentation MP:0001186 9.35 BTD OTC PAH PCBD1 PTS
Sources

Drugs & Therapeutics for Phenylketonuria

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

(show all 42)
# 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 1994-09-7, 94-09-7 2337
4
Melatonin Approved, Nutraceutical, Vet_approved Phase 4 73-31-4 896
5 Pharmaceutical Solutions Phase 4
6
Serotonin Investigational, Nutraceutical Phase 4 50-67-9 5202
7 Anticoagulants Phase 3
8 Plasma Substitutes Phase 3
9 Dextrans Phase 3
10 Blood Substitutes Phase 3
11 Hematinics Phase 1, Phase 2
12 Liver Extracts Phase 1, Phase 2
13
Moxifloxacin Approved, Investigational Phase 1 151096-09-2, 354812-41-2 152946
14
Nitric Oxide Approved Phase 1 10102-43-9 145068
15 Anti-Bacterial Agents Phase 1
16 Anti-Infective Agents Phase 1
17 Norgestimate, ethinyl estradiol drug combination Phase 1
18
Coal tar Approved 8007-45-2
19
Methylcobalamin Approved, Investigational 13422-55-4
20
Hydroxocobalamin Approved 13422-51-0 11953898 15589840
21
Tyrosine Approved, Investigational, Nutraceutical 60-18-4 6057
22
Cyanocobalamin Approved, Nutraceutical 68-19-9 44176380
23
Phenylalanine Approved, Investigational, Nutraceutical 63-91-2 6140
24
Lysine Approved, Nutraceutical 56-87-1 5962
25
arachidonic acid Experimental 506-32-1 444899
26
Cobalamin Experimental 13408-78-1 6857388
27 Sunflower
28 Soy Bean
29 Fluorodeoxyglucose F18
30 Whey Protein
31 Antioxidants
32 Dermatologic Agents
33 Keratolytic Agents
34 Omega 3 Fatty Acid
35 Nutrients
36 Vitamins
37 Trace Elements
38 Micronutrients
39 Caseins
40 Vitamin B Complex
41 Vitamin B 12
42 Vitamin B12

Interventional clinical trials:

(show top 50) (show all 117)
# 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 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
4 The Effectiveness of High-Dose Synthetic BH4 (Saproterin Dihydrochloride or "Kuvan") in Amish PKU Patients Recruiting NCT02677870 Phase 4 saproterin dihydrochloride
5 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®
6 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
7 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
8 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
9 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
10 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
11 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®
12 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
13 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®
14 An Open-label Extension Study to Evaluate the Safety and Efficacy of Subcutaneous Injections of Pegvaliase (> 40 mg/Day Dose) in Adults With Phenylketonuria Completed NCT03694353 Phase 3 Pegvaliase
15 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
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 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
18 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)
19 A Phase 1/2, Open-Label, Randomized Parallel Arm, Intra-patient Dose Escalation Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of CNSA-001(Sepiapterin) in Primary Tetrahydrobiopterin Deficient Patients With Hyperphenylalaninemia Completed NCT03519711 Phase 1, Phase 2 CNSA-001
20 Phase 2, Multicenter, Open Label Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to Primary BH4 Deficiency Completed NCT00355264 Phase 2 Phenoptin
21 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
22 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
23 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
24 Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response Completed NCT00841100 Phase 2 Kuvan
25 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
26 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
27 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
28 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
29 Hepatocyte Transplantation for Phenylketonuria Recruiting NCT01465100 Phase 1, Phase 2 Immunosuppression
30 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
31 An Open-label Study of the Efficacy and Safety of SYNB1618 in Patients With Phenylketonuria (SynPheny-1) Recruiting NCT04534842 Phase 2 SYNB1618
32 A Phase 1/2 Open-Label, Dose Escalation Study to Determine the Safety and Efficacy of BMN 307, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Phenylalanine Hydroxylase in Subjects With Phenylketonuria Recruiting NCT04480567 Phase 1, Phase 2 BMN 307
33 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
34 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
35 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
36 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). Completed NCT04085666 Phase 1 CDX 6114
37 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
38 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
39 Role of Nitric Oxide Coupling in Muscle Dysfunction With COPD Not yet recruiting NCT04014712 Phase 1 Tetrahydrobiopterin;Placebo oral tablet
40 Response to Phenylketonuria to Tetrahydrobiopterin (BH4) Terminated NCT00244218 Phase 1 tetrahydrobiopterin (BH4)
41 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). Withdrawn NCT04256655 Phase 1 cohort 1 0.225g;Cohort 2 0.75g;Cohort 3 2.25 g
42 - 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
43 Sapropterin Expanded Access Program Approved for marketing NCT00484991 Sapropterin dihydrochloride
44 Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia Completed NCT01869972
45 Effects of Sapropterin on Brain and Cognition in Individuals With Phenylketonuria Completed NCT00730080 Sapropterin (Kuvan)
46 Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria Completed NCT00909012
47 Study of a Phenylalanine Restricted Diet During Pregnancy to Prevent Symptoms in Offspring of Patients With Phenylketonuria Completed NCT00006142
48 Evaluation of Behavior, Executive Function, Neurotransmitter Function and Genomic Expression in PKU "Nonresponders" to Kuvan® (Sapropterin Dihydrochloride) Completed NCT01274026 sapropterin dihydrochloride
49 5-year Follow-up of the Comparison of Life and Physical Health in Adult Patients With PKU and Healthy Age Matched Controls Completed NCT01096758
50 Nutrition Status of Adult and Adolescent Patients With Classical Phenylketonuria (PKU) and Hyperphenylalaninemia Completed NCT01879995

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
2 Maternal Phenylketonuria 29
Sources

Anatomical Context for Phenylketonuria

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MalaCards organs/tissues related to Phenylketonuria:

40
Brain, Heart, Bone, Skin, Cortex, Kidney, Pituitary
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

About this section

Articles related to Phenylketonuria:

(show top 50) (show all 5958)
# Title Authors PMID Year
1
Molecular structure and polymorphic map of the human phenylalanine hydroxylase gene. 57 6 61 25
3008810 1986
2
Molecular genetics of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. 61 54 57 6
17935162 2008
3
Tetrahydrobiopterin responsiveness in phenylketonuria. Two new cases and a review of molecular genetic findings. 57 6 61 54
11999982 2002
4
A comprehensive study of phenylalanine hydroxylase gene mutations in the Iranian phenylketonuria patients. 6 61 57
30389586 2019
5
Long-term follow-up and outcome of phenylketonuria patients on sapropterin: a retrospective study. 61 57 6
23690520 2013
6
Pahenu1 is a mouse model for tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency and promotes analysis of the pharmacological chaperone mechanism in vivo. 6 57 61
20179079 2010
7
Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability. 61 57 6
18538294 2008
8
Predicted effects of missense mutations on native-state stability account for phenotypic outcome in phenylketonuria, a paradigm of misfolding diseases. 6 61 57
17924342 2007
9
Phenylalanine hydroxylase deficiency exhibits mutation heterogeneity in two large old order Amish settlements. 57 6 61
17630668 2007
10
Molecular and phenotypic characteristics of patients with phenylketonuria in Serbia and Montenegro. 6 57 61
16879198 2006
11
Biopterin responsive phenylalanine hydroxylase deficiency. 61 6 57
14726806 2004
12
Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. 6 57 61
12501224 2002
13
Congenital heart disease in maternal phenylketonuria: report from the Maternal PKU Collaborative Study. 6 57 61
11328945 2001
14
Effect of genotype on changes in intelligence quotient after dietary relaxation in phenylketonuria and hyperphenylalaninaemia. 61 6 57
10685924 2000
15
A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype. 25 54 61 6
9634518 1998
16
Mutation at the phenylalanine hydroxylase gene (PAH) and its use to document population genetic variation: the Quebec experience. 6 57 61
9781015 1998
17
A molecular survey of phenylketonuria in Iceland: identification of a founding mutation and evidence of predominant Norse settlement. 6 57 61
9450182 1997
18
Phenylketonuria and the peoples of Northern Ireland. 61 57 6
9254847 1997
19
Sequence variation at the phenylalanine hydroxylase gene in the British Isles. 61 57 6
9012412 1997
20
Phenylketonuria in a low incidence population: molecular characterisation of mutations in Finland. 61 57 6
8825928 1995
21
Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria. 6 61 57
8098245 1993
22
Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene. 57 6 61
1301187 1992
23
Illegitimate transcription of phenylalanine hydroxylase for detection of mutations in patients with phenylketonuria. 6 57 61
1301202 1992
24
Silent mutations in the phenylalanine hydroxylase gene as an aid to the diagnosis of phenylketonuria. 6 57 61
1682495 1991
25
Mutation detection in phenylketonuria by using chemical cleavage of mismatch: importance of using probes from both normal and patient samples. 57 6 61
2063869 1991
26
Maternal phenylketonuria syndrome in cousins caused by mild, unrecognized phenylketonuria in their mothers homozygous for the phenylalanine hydroxylase Arg-261-Gln mutation. 61 6 57
1915502 1991
27
Phenylketonuria in U.S. blacks: molecular analysis of the phenylalanine hydroxylase gene. 57 6 61
2014802 1991
28
CpG dinucleotides are mutation hot spots in phenylketonuria. 57 6 61
2574153 1989
29
Phenylalanine hydroxylase deficiency: diagnosis and management guideline. 61 25 57
24385074 2014
30
Influence of PAH Genotype on Sapropterin Response in PKU: Results of a Single-Center Cohort Study. 6 61 25
24190797 2014
31
Variations in genotype-phenotype correlations in phenylketonuria patients. 61 25 6
20082265 2010
32
Psychiatric symptoms and disorders in phenylketonuria. 61 25 57
20123472 2010
33
Identification and characterization of large deletions in the phenylalanine hydroxylase (PAH) gene by MLPA: evidence for both homologous and non-homologous mechanisms of rearrangement. 6 25 61
16931086 2006
34
Tetrahydrobiopterin responsiveness in patients with phenylketonuria. 61 6 25
15589814 2004
35
Short-term dietary interventions in children and adolescents with treated phenylketonuria: effects on neuropsychological outcome of a well-controlled population. 61 25 57
12555935 2002
36
Individual blood-brain barrier phenylalanine transport in siblings with classical phenylketonuria. 61 57 25
12555936 2002
37
Phenylketonuria in adulthood: a collaborative study. 61 25 57
12408183 2002
38
Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine. 6 57
11326337 2001
39
Structure/function analysis of the domains required for the multimerisation of phenylalanine hydroxylase. 6 25 61
9540801 1998
40
In vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to function. 61 25 6
9450897 1998
41
Human phenylalanine hydroxylase mutations and hyperphenylalaninemia phenotypes: a metanalysis of genotype-phenotype correlations. 25 6 61
9399896 1997
42
Recurrent mutation, gene conversion, or recombination at the human phenylalanine hydroxylase locus: evidence in French-Canadians and a catalog of mutations. 6 57
1971147 1990
43
Unresponsiveness to tetrahydrobiopterin of phenylalanine hydroxylase deficiency. 61 54 6
19913839 2010
44
[Mutation spectrum of phenylalanine hydroxylase gene in patients with phenylketonuria in Tianjin and surrounding areas of Northern China]. 61 54 6
20140859 2010
45
[Mutation analysis of the PAH gene in patients with phenylketonuria in Gansu province]. 61 6 54
20017307 2009
46
Genotype-predicted tetrahydrobiopterin (BH4)-responsiveness and molecular genetics in Croatian patients with phenylalanine hydroxylase (PAH) deficiency. 6 61 54
19394257 2009
47
A limited spectrum of phenylalanine hydroxylase mutations is observed in phenylketonuria patients in western Poland and implications for treatment with 6R tetrahydrobiopterin. 6 54 61
19444284 2009
48
Predicting a clinical/biochemical phenotype for PKU/MHP patients with PAH gene mutations. 61 54 6
19062537 2008
49
Mutation analysis of PAH gene and characterization of a recurrent deletion mutation in Korean patients with phenylketonuria. 6 54 61
18985011 2008
50
A mutation analysis of the phenylalanine hydroxylase (PAH) gene in the Israeli population. 54 61 6
18294361 2008
Sources

Variations for Phenylketonuria

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ClinVar genetic disease variations for Phenylketonuria:

6 (show top 50) (show all 771)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PAH NM_000277.3(PAH):c.1315+1G>A SNV Pathogenic 576 rs5030861 GRCh37: 12:103234177-103234177
GRCh38: 12:102840399-102840399
2 PAH NM_000277.3(PAH):c.1222C>T (p.Arg408Trp) SNV Pathogenic 577 rs5030858 GRCh37: 12:103234271-103234271
GRCh38: 12:102840493-102840493
3 PAH NM_000277.3(PAH):c.932T>C (p.Leu311Pro) SNV Pathogenic 578 rs62642936 GRCh37: 12:103240710-103240710
GRCh38: 12:102846932-102846932
4 PAH NM_000277.3(PAH):c.977G>A (p.Trp326Ter) SNV Pathogenic 579 rs62514959 GRCh37: 12:103238202-103238202
GRCh38: 12:102844424-102844424
5 PAH NM_000277.3(PAH):c.838G>A (p.Glu280Lys) SNV Pathogenic 580 rs62508698 GRCh37: 12:103246597-103246597
GRCh38: 12:102852819-102852819
6 PAH NM_000277.3(PAH):c.331C>T (p.Arg111Ter) SNV Pathogenic 581 rs76296470 GRCh37: 12:103288534-103288534
GRCh38: 12:102894756-102894756
7 PAH NM_000277.3(PAH):c.782G>A (p.Arg261Gln) SNV Pathogenic 582 rs5030849 GRCh37: 12:103246653-103246653
GRCh38: 12:102852875-102852875
8 PAH NM_000277.3(PAH):c.754C>T (p.Arg252Trp) SNV Pathogenic 584 rs5030847 GRCh37: 12:103246681-103246681
GRCh38: 12:102852903-102852903
9 PAH NM_000277.3(PAH):c.169-4949_352+1467delinsGGCACCTG Indel Pathogenic 585 GRCh37: 12:103287046-103293645
GRCh38: 12:102893268-102899867
10 PAH NM_000277.3(PAH):c.1A>G (p.Met1Val) SNV Pathogenic 586 rs62514891 GRCh37: 12:103310908-103310908
GRCh38: 12:102917130-102917130
11 PAH NM_000277.3(PAH):c.473G>A (p.Arg158Gln) SNV Pathogenic 587 rs5030843 GRCh37: 12:103260410-103260410
GRCh38: 12:102866632-102866632
12 PAH NM_000277.3(PAH):c.727C>T (p.Arg243Ter) SNV Pathogenic 588 rs5030846 GRCh37: 12:103246708-103246708
GRCh38: 12:102852930-102852930
13 PAH NM_000277.3(PAH):c.611A>G (p.Tyr204Cys) SNV Pathogenic 590 rs62514927 GRCh37: 12:103249009-103249009
GRCh38: 12:102855231-102855231
14 PAH NM_000277.3(PAH):c.728G>A (p.Arg243Gln) SNV Pathogenic 591 rs62508588 GRCh37: 12:103246707-103246707
GRCh38: 12:102852929-102852929
15 PAH NM_000277.3(PAH):c.1238G>C (p.Arg413Pro) SNV Pathogenic 592 rs79931499 GRCh37: 12:103234255-103234255
GRCh38: 12:102840477-102840477
16 PAH NM_000277.3(PAH):c.442-1G>A SNV Pathogenic 594 rs62514907 GRCh37: 12:103260442-103260442
GRCh38: 12:102866664-102866664
17 PAH NM_000277.3(PAH):c.1068C>G (p.Tyr356Ter) SNV Pathogenic 595 rs62516095 GRCh37: 12:103237555-103237555
GRCh38: 12:102843777-102843777
18 PAH NM_000277.3(PAH):c.814G>T (p.Gly272Ter) SNV Pathogenic 596 rs62514952 GRCh37: 12:103246621-103246621
GRCh38: 12:102852843-102852843
19 PAH NM_000277.3(PAH):c.842+1G>A SNV Pathogenic 599 rs5030852 GRCh37: 12:103246592-103246592
GRCh38: 12:102852814-102852814
20 PAH NM_000277.3(PAH):c.1197A>T (p.Val399=) SNV Pathogenic 601 rs199475584 GRCh37: 12:103237426-103237426
GRCh38: 12:102843648-102843648
21 PAH NM_000277.3(PAH):c.829T>G (p.Tyr277Asp) SNV Pathogenic 603 rs78655458 GRCh37: 12:103246606-103246606
GRCh38: 12:102852828-102852828
22 PAH NM_000277.3(PAH):c.281_283TCA[1] (p.Ile95del) Microsatellite Pathogenic 604 rs62508727 GRCh37: 12:103288579-103288581
GRCh38: 12:102894801-102894803
23 PAH NM_000277.3(PAH):c.117C>G (p.Phe39Leu) SNV Pathogenic 605 rs62642926 GRCh37: 12:103306620-103306620
GRCh38: 12:102912842-102912842
24 PAH PAH, SER349ARG Variation Pathogenic 606 GRCh37:
GRCh38:
25 PAH NM_000277.3(PAH):c.1066-11G>A SNV Pathogenic 607 rs5030855 GRCh37: 12:103237568-103237568
GRCh38: 12:102843790-102843790
26 PAH NM_000277.3(PAH):c.143T>C (p.Leu48Ser) SNV Pathogenic 608 rs5030841 GRCh37: 12:103306594-103306594
GRCh38: 12:102912816-102912816
27 PAH NM_000277.3(PAH):c.781C>T (p.Arg261Ter) SNV Pathogenic 610 rs5030850 GRCh37: 12:103246654-103246654
GRCh38: 12:102852876-102852876
28 PAH NM_000277.3(PAH):c.165del (p.Phe55fs) Deletion Pathogenic 611 rs199475566 GRCh37: 12:103306572-103306572
GRCh38: 12:102912794-102912794
29 PAH NM_000277.3(PAH):c.1223G>A (p.Arg408Gln) SNV Pathogenic 612 rs5030859 GRCh37: 12:103234270-103234270
GRCh38: 12:102840492-102840492
30 PAH NM_000277.3(PAH):c.896T>G (p.Phe299Cys) SNV Pathogenic 613 rs62642933 GRCh37: 12:103245481-103245481
GRCh38: 12:102851703-102851703
31 PAH NM_000277.3(PAH):c.842+2T>A SNV Pathogenic 614 rs62514955 GRCh37: 12:103246591-103246591
GRCh38: 12:102852813-102852813
32 PAH NM_000277.3(PAH):c.965C>G (p.Ala322Gly) SNV Pathogenic 616 rs62514958 GRCh37: 12:103240677-103240677
GRCh38: 12:102846899-102846899
33 PAH NM_000277.3(PAH):c.1162G>A (p.Val388Met) SNV Pathogenic 619 rs62516101 GRCh37: 12:103237461-103237461
GRCh38: 12:102843683-102843683
34 PAH NM_000277.3(PAH):c.1169A>G (p.Glu390Gly) SNV Pathogenic 625 rs5030856 GRCh37: 12:103237454-103237454
GRCh38: 12:102843676-102843676
35 PAH NM_000277.3(PAH):c.1076C>G (p.Ser359Ter) SNV Pathogenic 626 rs5030854 GRCh37: 12:103237547-103237547
GRCh38: 12:102843769-102843769
36 PAH NM_000277.3(PAH):c.293T>C (p.Leu98Ser) SNV Pathogenic 627 rs62517167 GRCh37: 12:103288572-103288572
GRCh38: 12:102894794-102894794
37 PAH NM_000277.3(PAH):c.136G>A (p.Gly46Ser) SNV Pathogenic 629 rs74603784 GRCh37: 12:103306601-103306601
GRCh38: 12:102912823-102912823
38 PAH NM_000277.3(PAH):c.1129del (p.Tyr377fs) Deletion Pathogenic 634 rs62642941 GRCh37: 12:103237494-103237494
GRCh38: 12:102843716-102843716
39 PAH NM_000277.3(PAH):c.3G>A (p.Met1Ile) SNV Pathogenic 622 rs62514893 GRCh37: 12:103310906-103310906
GRCh38: 12:102917128-102917128
40 PAH NM_000277.3(PAH):c.194T>C (p.Ile65Thr) SNV Pathogenic 636 rs75193786 GRCh37: 12:103288671-103288671
GRCh38: 12:102894893-102894893
41 PAH NM_000277.1(PAH):c.913_1199del (p.Ile306Leufs) Deletion Pathogenic 637 GRCh37:
GRCh38: 12:102840516-102851686
42 PAH NM_000277.3(PAH):c.1066-2A>T SNV Pathogenic 120258 rs281865447 GRCh37: 12:103237559-103237559
GRCh38: 12:102843781-102843781
43 PAH NM_000277.3(PAH):c.196G>T (p.Glu66Ter) SNV Pathogenic 120270 rs281865454 GRCh37: 12:103288669-103288669
GRCh38: 12:102894891-102894891
44 PAH NM_000277.3(PAH):c.169G>T (p.Glu57Ter) SNV Pathogenic 120268 rs140945592 GRCh37: 12:103288696-103288696
GRCh38: 12:102894918-102894918
45 PAH NM_000277.3(PAH):c.350del (p.Thr117fs) Deletion Pathogenic 120274 rs281865428 GRCh37: 12:103288515-103288515
GRCh38: 12:102894737-102894737
46 PAH NM_000277.3(PAH):c.442-2A>C SNV Pathogenic 120276 rs281865448 GRCh37: 12:103260443-103260443
GRCh38: 12:102866665-102866665
47 PAH NM_000277.3(PAH):c.504C>A (p.Tyr168Ter) SNV Pathogenic 120277 rs281865455 GRCh37: 12:103260379-103260379
GRCh38: 12:102866601-102866601
48 PAH NM_000277.3(PAH):c.837del (p.Glu280fs) Deletion Pathogenic 120288 rs281865429 GRCh37: 12:103246598-103246598
GRCh38: 12:102852820-102852820
49 PAH NM_000277.3(PAH):c.912+2T>C SNV Pathogenic 120292 rs281865449 GRCh37: 12:103245463-103245463
GRCh38: 12:102851685-102851685
50 PAH NM_000277.3(PAH):c.916del (p.Ile306fs) Deletion Pathogenic 120296 rs281865456 GRCh37: 12:103240726-103240726
GRCh38: 12:102846948-102846948

UniProtKB/Swiss-Prot genetic disease variations for Phenylketonuria:

72 (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 rs156585349
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

About this section

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:

(show all 14)
# Super pathways Score Top Affiliating Genes
1
Viral mRNA Translation 65
Show member pathways
 13.63 TPH1 TH SLC7A5 QDPR PCBD1 PAH
2
Metabolism 65
Show member pathways
 13.61 TTR TPH1 TH SLC7A5 QDPR PTS
3
Carbon metabolism 36
Show member pathways
 12.1 PAH OTC MTHFR G6PD
4
Biosynthesis of cofactors 36
Show member pathways
 11.98 PTS HPD GCH1 ADSL
5
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways 1
11.93 TPH1 TH PAH HADHA ACADM
6
Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism 65
Show member pathways
 11.72 SLC7A5 QDPR PCBD1 PAH HPD HGD
7
Tryptophan metabolism 1 36
Show member pathways
 11.65 TPH1 MAOB HADHA
8
Amino Acid metabolism 1
11.63 TPH1 TH OTC ACADM
9
Phenylalanine metabolism 36
Show member pathways
 11.56 TH PAH MAOB HPD HGD
10
FOXA2 and FOXA3 transcription factor networks 1
11.25 TTR ALB ACADM
11
Biogenic Amine Synthesis 1
Show member pathways
 10.92 TPH1 TH PAH
12
Dopamine metabolism 1
10.67 TH MAOB
13
Folate biosynthesis 36
Show member pathways
 10.63 TPH1 TH QDPR PTS PCBD1 PAH
14
Beta oxidation of octanoyl-CoA to hexanoyl-CoA 65
Show member pathways
 10.49 HADHA ACADM
Sources

GO Terms for Phenylketonuria

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

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.61 TTR SLC7A5 QDPR PCBD1 HPD HGD
2 cytosol GO:0005829 9.44 TPH1 TH SLC7A5 QDPR PTS PCBD1

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

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 metabolic process GO:0008152 9.8 PAH MTHFR HADHA GCH1
2 response to drug GO:0042493 9.8 TH OTC MTHFR MAOB HADHA
3 response to ethanol GO:0045471 9.74 TH MAOB G6PD
4 liver development GO:0001889 9.71 QDPR OTC ACADM
5 cellular amino acid metabolic process GO:0006520 9.62 QDPR PTS OTC HGD
6 response to corticosterone GO:0051412 9.56 TH MAOB
7 aromatic amino acid family metabolic process GO:0009072 9.56 TPH1 TH PAH HPD
8 neurotransmitter biosynthetic process GO:0042136 9.55 TH PAH
9 thyroid hormone transport GO:0070327 9.52 TTR SLC7A5
10 dopamine biosynthetic process GO:0042416 9.51 TH GCH1
11 catecholamine biosynthetic process GO:0042423 9.48 TH PAH
12 tyrosine catabolic process GO:0006572 9.46 HPD HGD
13 tetrahydrobiopterin biosynthetic process GO:0006729 9.46 QDPR PTS PCBD1 GCH1
14 response to aluminum ion GO:0010044 9.43 QDPR MAOB
15 oxidation-reduction process GO:0055114 9.4 TPH1 TH QDPR PCBD1 PAH MTHFR
16 dihydrobiopterin metabolic process GO:0051066 9.37 QDPR GCH1
17 L-phenylalanine catabolic process GO:0006559 9.35 QDPR PCBD1 PAH HPD HGD

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

# Name GO ID Score Top Affiliating Genes
1 catalytic activity GO:0003824 9.83 PAH MTHFR HADHA GCH1 ADSL
2 identical protein binding GO:0042802 9.77 TTR TH QDPR PTS PCBD1 OTC
3 lyase activity GO:0016829 9.62 PTS PCBD1 HADHA ADSL
4 monooxygenase activity GO:0004497 9.58 TPH1 TH PAH
5 flavin adenine dinucleotide binding GO:0050660 9.54 MTHFR MAOB ACADM
6 oxidoreductase activity GO:0016491 9.36 TPH1 TH QDPR PAH MTHFR MAOB
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 9.33 TPH1 TH PAH
8 phenylalanine 4-monooxygenase activity GO:0004505 9.26 PCBD1 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
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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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