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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 74 20 43 58 73 36 29 13 6 42 15 37 39
Phenylalanine Hydroxylase Deficiency 57 74 25 20 43 58
Pku 57 12 20 43 58 73
Pah Deficiency 57 25 43 58
Maternal Phenylketonuria 12 58 29
Phenylketonurias 54 44 71
Folling Disease 57 20 43
Hyperphenylalaninemia, Non-Pku Mild 57 6
Oligophrenia Phenylpyruvica 57 20
Phenylketonuria, Maternal 44 71
Variant Phenylketonuria 20 58
Mild Phenylketonuria 20 58
Folling's Disease 12 43
Phenylalaninemia 12 74
Variant Pku 20 58
Mild Pku 20 58
Mpku 20 58
Deficiency Disease, Phenylalanine Hydroxylase 43
Phenylalanine Hydroxylase Deficiency Disease 43
Non-Phenylketonuria Hyperphenylalaninemia 73
Hyperphenylalaninemic Embryopathy 58
Maternal Hyperphenylalaninemia 58
Phenylketonuric Embryopathy 58
Classical Phenylketonuria 71
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®:

57 (Updated 05-Mar-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 05-Mar-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 : 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 605)
# 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 31.9 TH GCH1
4 dystonia, dopa-responsive, due to sepiapterin reductase deficiency 31.9 QDPR PCBD1 GCH1
5 hyperphenylalaninemia, bh4-deficient, a 31.9 QDPR PTS PCBD1 PAH GCH1
6 hyperphenylalaninemia 31.7 TPH1 TH QDPR PTS PCBD1 PAH
7 amino acid metabolic disorder 31.4 PAH OTC MTHFR HPD BTD ALB
8 mild hyperphenylalaninemia 31.2 QDPR PTS PCBD1 PAH
9 congenital hypothyroidism 30.9 G6PD BTD ALB ACADM
10 galactosemia i 30.6 PAH G6PD BTD ACADM
11 tyrosinemia 30.5 QDPR PTS PAH HPD BTD
12 tetrahydrobiopterin deficiency 30.4 TH QDPR PTS PCBD1 PAH GCH1
13 keratomalacia 30.3 TTR QDPR
14 sleep disorder 30.2 TH MAOB GCH1 ALB
15 alkaptonuria 30.2 PAH HPD ADSL
16 psychotic disorder 30.2 TPH1 TH PAH MTHFR MAOB
17 personality disorder 30.1 TPH1 TH MAOB
18 dystonia 30.1 TPH1 TH QDPR PTS PCBD1 PAH
19 nutritional deficiency disease 30.0 TTR MTHFR BGLAP ALB
20 west syndrome 30.0 TPH1 TH MTHFR BTD
21 abdominal obesity-metabolic syndrome 1 30.0 PTS PAH OTC HADHA BTD ACADM
22 enteropathica 30.0 OTC ALB
23 metabolic acidosis 29.9 BTD BGLAP ALB
24 homocystinuria 29.9 OTC MTHFR HADHA BTD ALB ADSL
25 acyl-coa dehydrogenase, medium-chain, deficiency of 29.7 PAH HADHA BTD ACADM
26 biotinidase deficiency 29.7 HADHA BTD ADSL
27 glycogen storage disease 29.7 OTC MTHFR BTD ALB
28 maple syrup urine disease 29.6 SLC7A5 QDPR PAH OTC HADHA BTD
29 parkinson disease, late-onset 29.5 TTR TPH1 TH QDPR PAH MAOB
30 methylmalonic acidemia 29.4 PAH OTC MTHFR HADHA ACADM
31 disease of mental health 29.3 TTR TPH1 TH PAH MTHFR MAOB
32 hyperphenylalaninemia, bh4-deficient, d 11.8
33 hyperphenylalaninemia, mild, non-bh4-deficient 11.5
34 maternal hyperphenylalaninemia 11.4
35 gtp cyclohydrolase 1-deficient dopa-responsive dystonia 11.2
36 hyperphenylalaninemia, bh4-deficient, c 11.2
37 tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria 11.1
38 microcephaly 11.1
39 dystonia, dopa-responsive 11.0
40 hpa i recognition polymorphism, beta-globin-related 11.0
41 spasticity 10.9
42 glycine encephalopathy 10.9
43 tyrosine-oxidase temporary deficiency 10.9
44 thrombocytopenia 10.8
45 fetal and neonatal alloimmune thrombocytopenia 10.6
46 purpura 10.6
47 inherited metabolic disorder 10.6
48 autosomal recessive disease 10.5
49 hypothyroidism 10.5
50 alacrima, achalasia, and mental retardation syndrome 10.5

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 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 05-Mar-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 05-Mar-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 9.64 ADSL
2 Decreased viability GR00249-S 9.64 ACADM ALB G6PD MAOB 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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.35 ACADM ALB BGLAP BTD G6PD GCH1
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 9.8 ACADM ALB GCH1 HADHA MTHFR OTC
6 pigmentation MP:0001186 9.35 BTD OTC PAH PCBD1 PTS
7 renal/urinary system MP:0005367 9.28 ALB BTD HADHA HPD MAOB OTC
Sources

Drugs & Therapeutics for Phenylketonuria

About this section

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

Interventional clinical trials:

(show top 50) (show all 116)
# 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 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®
11 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
12 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
13 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®
14 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
15 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
16 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
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 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
23 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
24 Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response Completed NCT00841100 Phase 2 Kuvan
25 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
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 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 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 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
34 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
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 Study of a Phenylalanine Restricted Diet During Pregnancy to Prevent Symptoms in Offspring of Patients With Phenylketonuria Completed NCT00006142
47 Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria Completed NCT00909012
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 PAH
2 Maternal Phenylketonuria 29
Sources

Anatomical Context for Phenylketonuria

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MalaCards organs/tissues related to Phenylketonuria:

40
Brain, Heart, Bone, Liver, Cortex, Skin, Endothelial
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 5839)
# Title Authors PMID Year
1
Molecular structure and polymorphic map of the human phenylalanine hydroxylase gene. 57 25 61 6
3008810 1986
2
A comprehensive study of phenylalanine hydroxylase gene mutations in the Iranian phenylketonuria patients. 61 57 6
30389586 2019
3
Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability. 6 57 61
18538294 2008
4
Phenylalanine hydroxylase deficiency exhibits mutation heterogeneity in two large old order Amish settlements. 61 57 6
17630668 2007
5
Molecular and phenotypic characteristics of patients with phenylketonuria in Serbia and Montenegro. 61 6 57
16879198 2006
6
A molecular survey of phenylketonuria in Iceland: identification of a founding mutation and evidence of predominant Norse settlement. 6 61 57
9450182 1997
7
Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria. 6 57 61
8098245 1993
8
Illegitimate transcription of phenylalanine hydroxylase for detection of mutations in patients with phenylketonuria. 61 57 6
1301202 1992
9
Silent mutations in the phenylalanine hydroxylase gene as an aid to the diagnosis of phenylketonuria. 57 6 61
1682495 1991
10
Mutation detection in phenylketonuria by using chemical cleavage of mismatch: importance of using probes from both normal and patient samples. 61 6 57
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 57 6
1915502 1991
12
Phenylketonuria in U.S. blacks: molecular analysis of the phenylalanine hydroxylase gene. 6 57 61
2014802 1991
13
CpG dinucleotides are mutation hot spots in phenylketonuria. 57 6 61
2574153 1989
14
Phenylalanine hydroxylase deficiency: diagnosis and management guideline. 57 25 61
24385074 2014
15
Psychiatric symptoms and disorders in phenylketonuria. 61 25 57
20123472 2010
16
Individual blood-brain barrier phenylalanine transport in siblings with classical phenylketonuria. 61 25 57
12555936 2002
17
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
18
Phenylketonuria in adulthood: a collaborative study. 57 61 25
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 57
1971147 1990
20
Molecular genetics of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. 54 57 61
17935162 2008
21
Tetrahydrobiopterin responsiveness in phenylketonuria. Two new cases and a review of molecular genetic findings. 57 54 61
11999982 2002
22
A silent mutation induces exon skipping in the phenylalanine hydroxylase gene in phenylketonuria. 54 61 6
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. 54 61 57
10720436 2000
24
Gypsy phenylketonuria: a point mutation of the phenylalanine hydroxylase gene in Gypsy families from Slovakia. 6 61 54
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 identification of two mis-sense mutations at the PAH gene locus in a Turkish patient with phenylketonuria. 54 61 6
1679030 1991
27
The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations. 54 61 57
1679029 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. 6 61 54
1709636 1991
30
Founder effect of a prevalent phenylketonuria mutation in the Oriental population. 6 54 61
2006152 1991
31
Two mutations within the coding sequence of the phenylalanine hydroxylase gene. 6 54 61
1975559 1990
32
Prenatal detection of an Arg----Ter mutation at codon 111 of the PAH gene using DNA amplification. 61 54 6
1975096 1990
33
Molecular genetics of PKU in eastern Europe: a nonsense mutation associated with haplotype 4 of the phenylalanine hydroxylase gene. 61 6 54
2309142 1990
34
Long-term comparative effectiveness of pegvaliase versus standard of care comparators in adults with phenylketonuria. 57 61
31439512 2019
35
Vitamin and mineral status in patients with hyperphenylalaninemia. 61 57
26123187 2015
36
Recommendations for the nutrition management of phenylalanine hydroxylase deficiency. 57 61
24385075 2014
37
Long-term follow-up and outcome of phenylketonuria patients on sapropterin: a retrospective study. 61 57
23690520 2013
38
Phenylketonuria. 61 57
20971365 2010
39
Pahenu1 is a mouse model for tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency and promotes analysis of the pharmacological chaperone mechanism in vivo. 57 61
20179079 2010
40
Animal models of brain dysfunction in phenylketonuria. 57 61
20123463 2010
41
Psychosocial aspects of PKU: hidden disabilities--a review. 57 61
20123473 2010
42
Predicted effects of missense mutations on native-state stability account for phenotypic outcome in phenylketonuria, a paradigm of misfolding diseases. 61 57
17924342 2007
43
The PAH gene, phenylketonuria, and a paradigm shift. 57 61
17443661 2007
44
Efficiency of long-term tetrahydrobiopterin monotherapy in phenylketonuria. 61 57
15303001 2004
45
Biopterin responsive phenylalanine hydroxylase deficiency. 61 57
14726806 2004
46
Cerebral energy metabolism in phenylketonuria: findings by quantitative In vivo 31P MR spectroscopy. 57 61
12612190 2003
47
Genetic diversity within the R408W phenylketonuria mutation lineages in Europe. 6 61
12655548 2003
48
Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. 61 57
12501224 2002
49
The impact of the control of serum phenylalanine levels on osteopenia in patients with phenylketonuria. 57 61
12536994 2002
50
Congenital heart disease in maternal phenylketonuria: report from the Maternal PKU Collaborative Study. 57 61
11328945 2001
Sources

Variations for Phenylketonuria

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ClinVar genetic disease variations for Phenylketonuria:

6 (show top 50) (show all 743)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PAH NM_000277.3(PAH):c.977G>A (p.Trp326Ter) SNV Pathogenic 579 rs62514959 12:103238202-103238202 12:102844424-102844424
2 PAH PAH, SER349ARG Variation Pathogenic 606
3 PAH NM_000277.3(PAH):c.842+2T>A SNV Pathogenic 614 rs62514955 12:103246591-103246591 12:102852813-102852813
4 PAH NM_000277.3(PAH):c.1092_1106del (p.Leu365_Leu369del) Deletion Pathogenic 620 rs62516097 12:103237517-103237531 12:102843739-102843753
5 PAH NM_000277.3(PAH):c.1076C>G (p.Ser359Ter) SNV Pathogenic 626 rs5030854 12:103237547-103237547 12:102843769-102843769
6 PAH NM_000277.3(PAH):c.293T>C (p.Leu98Ser) SNV Pathogenic 627 rs62517167 12:103288572-103288572 12:102894794-102894794
7 PAH NM_000277.3(PAH):c.136G>A (p.Gly46Ser) SNV Pathogenic 629 rs74603784 12:103306601-103306601 12:102912823-102912823
8 PAH NM_000277.3(PAH):c.1129del (p.Tyr377fs) Deletion Pathogenic 634 rs62642941 12:103237494-103237494 12:102843716-102843716
9 PAH NM_000277.3(PAH):c.1220C>T (p.Pro407Leu) SNV Pathogenic 635 rs62644473 12:103234273-103234273 12:102840495-102840495
10 PAH NM_000277.1(PAH):c.913_1199del (p.Ile306Leufs) Deletion Pathogenic 637 12:102840516-102851686
11 PAH NM_000277.3(PAH):c.3G>A (p.Met1Ile) SNV Pathogenic 622 rs62514893 12:103310906-103310906 12:102917128-102917128
12 PAH NM_000277.3(PAH):c.1066-2A>T SNV Pathogenic 120258 rs281865447 12:103237559-103237559 12:102843781-102843781
13 PAH NM_000277.3(PAH):c.169G>T (p.Glu57Ter) SNV Pathogenic 120268 rs140945592 12:103288696-103288696 12:102894918-102894918
14 PAH NM_000277.3(PAH):c.196G>T (p.Glu66Ter) SNV Pathogenic 120270 rs281865454 12:103288669-103288669 12:102894891-102894891
15 PAH NM_000277.3(PAH):c.350del (p.Thr117fs) Deletion Pathogenic 120274 rs281865428 12:103288515-103288515 12:102894737-102894737
16 PAH NM_000277.3(PAH):c.442-2A>C SNV Pathogenic 120276 rs281865448 12:103260443-103260443 12:102866665-102866665
17 PAH NM_000277.3(PAH):c.837del (p.Glu280fs) Deletion Pathogenic 120288 rs281865429 12:103246598-103246598 12:102852820-102852820
18 PAH NM_000277.3(PAH):c.912+2T>C SNV Pathogenic 120292 rs281865449 12:103245463-103245463 12:102851685-102851685
19 PAH NM_000277.3(PAH):c.916del (p.Ile306fs) Deletion Pathogenic 120296 rs281865456 12:103240726-103240726 12:102846948-102846948
20 PAH NM_000277.3(PAH):c.927_928CT[2] (p.Leu311fs) Microsatellite Pathogenic 120297 rs281865430 12:103240710-103240711 12:102846932-102846933
21 PAH NM_000277.3(PAH):c.155del (p.Leu52fs) Deletion Pathogenic 120310 rs281865165 12:103306582-103306582 12:102912804-102912804
22 PAH NM_000277.3(PAH):c.847A>T (p.Ile283Phe) SNV Pathogenic 102876 rs62517168 12:103245530-103245530 12:102851752-102851752
23 PAH NM_000277.3(PAH):c.168+1G>A SNV Pathogenic 102604 rs62514898 12:103306568-103306568 12:102912790-102912790
24 PAH NM_000277.3(PAH):c.578_579CT[1] (p.Leu194fs) Microsatellite Pathogenic 102741 rs62508587 12:103249039-103249040 12:102855261-102855262
25 PAH NM_000277.3(PAH):c.694C>T (p.Gln232Ter) SNV Pathogenic 102788 rs62507348 12:103248926-103248926 12:102855148-102855148
26 PAH NM_000277.3(PAH):c.357del (p.Trp120fs) Deletion Pathogenic 197125 rs794727619 12:103271324-103271324 12:102877546-102877546
27 PAH NM_000277.3(PAH):c.648C>G (p.Tyr216Ter) SNV Pathogenic 102769 rs62509013 12:103248972-103248972 12:102855194-102855194
28 PAH NM_000277.3(PAH):c.168+5G>C SNV Pathogenic 102606 rs62507288 12:103306564-103306564 12:102912786-102912786
29 PAH NM_000277.3(PAH):c.1147C>T (p.Gln383Ter) SNV Pathogenic 370701 rs1037293795 12:103237476-103237476 12:102843698-102843698
30 PAH NM_000277.3(PAH):c.975C>G (p.Tyr325Ter) SNV Pathogenic 102921 rs62508573 12:103238204-103238204 12:102844426-102844426
31 PAH NM_000277.3(PAH):c.1065+1G>A SNV Pathogenic 102501 rs62516147 12:103238113-103238113 12:102844335-102844335
32 PAH NM_000277.3(PAH):c.1024del (p.Ala342fs) Deletion Pathogenic 102475 rs63581460 12:103238155-103238155 12:102844377-102844377
33 PAH NM_000277.3(PAH):c.558_559del (p.Trp187fs) Deletion Pathogenic 102734 rs62517207 12:103249061-103249062 12:102855283-102855284
34 PAH NM_000277.3(PAH):c.782G>C (p.Arg261Pro) SNV Pathogenic 102832 rs5030849 12:103246653-103246653 12:102852875-102852875
35 PAH NM_000277.3(PAH):c.498C>G (p.Tyr166Ter) SNV Pathogenic 371373 rs199475645 12:103260385-103260385 12:102866607-102866607
36 PAH NM_000277.3(PAH):c.398_401del (p.Asn133fs) Deletion Pathogenic 102663 rs199475605 12:103271280-103271283 12:102877502-102877505
37 PAH NC_000012.11:g.(?_103248894)_(103249130_?)del Deletion Pathogenic 458077 12:103248894-103249130
38 PAH NM_000277.3(PAH):c.737del (p.Ala246fs) Deletion Pathogenic 102814 rs199475666 12:103246698-103246698 12:102852920-102852920
39 PAH NM_000277.3(PAH):c.865G>A (p.Gly289Arg) SNV Pathogenic 458082 rs199475693 12:103245512-103245512 12:102851734-102851734
40 PAH NM_000277.3(PAH):c.553_706+647del Deletion Pathogenic 458079 12:103248267-103249067 12:102854489-102855289
41 PAH NM_000277.3(PAH):c.618C>G (p.Tyr206Ter) SNV Pathogenic 102763 rs62517201 12:103249002-103249002 12:102855224-102855224
42 PAH NM_000277.3(PAH):c.556del (p.Thr186fs) Deletion Pathogenic 102733 rs62507328 12:103249064-103249064 12:102855286-102855286
43 PAH NM_000277.3(PAH):c.592_613del (p.Tyr198fs) Deletion Pathogenic 102746 rs199475697 12:103249007-103249028 12:102855229-102855250
44 PAH NM_000277.3(PAH):c.839A>G (p.Glu280Gly) SNV Pathogenic 102866 rs62508734 12:103246596-103246596 12:102852818-102852818
45 PAH NM_000277.3(PAH):c.569T>C (p.Val190Ala) SNV Pathogenic 102740 rs62514919 12:103249051-103249051 12:102855273-102855273
46 PAH NM_000277.3(PAH):c.734T>A (p.Val245Glu) SNV Pathogenic 102811 rs76212747 12:103246701-103246701 12:102852923-102852923
47 PAH NM_000277.3(PAH):c.1340C>A (p.Ala447Asp) SNV Pathogenic 102595 rs76542238 12:103232972-103232972 12:102839194-102839194
48 PAH NM_000277.3(PAH):c.1199+1G>A SNV Pathogenic 102556 rs62509015 12:103237423-103237423 12:102843645-102843645
49 PAH NM_000277.3(PAH):c.707-12_711del Deletion Pathogenic 527863 rs1555204492 12:103246724-103246740 12:102852946-102852962
50 PAH NC_000012.12:g.(?_102854491)_(102855289_?)del Deletion Pathogenic 527864 12:103248269-103249067 12:102854491-102855289

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 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

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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:

(show all 13)
# Super pathways Score Top Affiliating Genes
1
Metabolism 65
Show member pathways
 13.59 TTR TPH1 TH SLC7A5 QDPR PTS
2
Carbon metabolism 36
Show member pathways
 12.1 PAH OTC MTHFR HADHA G6PD
3
Biosynthesis of cofactors 36
Show member pathways
 12 PTS HPD GCH1 ADSL
4
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways 1
11.86 TPH1 TH PAH HADHA ACADM
5
Amino Acid metabolism 1
11.66 TPH1 TH OTC ACADM
6
Tryptophan metabolism 1 36
Show member pathways
 11.65 TPH1 MAOB HADHA
7
Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism 65
Show member pathways
 11.64 SLC7A5 QDPR PCBD1 PAH HPD
8
Phenylalanine metabolism 36
Show member pathways
 11.52 TH PAH MAOB HPD
9
FOXA2 and FOXA3 transcription factor networks 1
11.28 TTR ALB ACADM
10
Biogenic Amine Synthesis 1
Show member pathways
 10.95 TPH1 TH PAH
11
Dopamine metabolism 1
10.67 TH MAOB
12
Folate biosynthesis 36
Show member pathways
 10.63 TPH1 TH QDPR PTS PCBD1 PAH
13
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 cytosol GO:0005829 9.4 TPH1 TH SLC7A5 QDPR PTS PCBD1

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

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 metabolic process GO:0008152 9.81 PAH MTHFR HADHA GCH1
2 response to drug GO:0042493 9.8 TH OTC MTHFR MAOB HADHA BGLAP
3 liver development GO:0001889 9.73 QDPR OTC ACADM
4 response to ethanol GO:0045471 9.73 TH MAOB G6PD BGLAP
5 response to nutrient levels GO:0031667 9.72 TH OTC BGLAP
6 cellular amino acid metabolic process GO:0006520 9.63 QDPR PTS OTC
7 response to corticosterone GO:0051412 9.58 TH MAOB
8 response to zinc ion GO:0010043 9.58 TH OTC BGLAP
9 neurotransmitter biosynthetic process GO:0042136 9.57 TH PAH
10 L-phenylalanine catabolic process GO:0006559 9.56 QDPR PCBD1 PAH HPD
11 thyroid hormone transport GO:0070327 9.54 TTR SLC7A5
12 dopamine biosynthetic process GO:0042416 9.52 TH GCH1
13 catecholamine biosynthetic process GO:0042423 9.49 TH PAH
14 response to aluminum ion GO:0010044 9.48 QDPR MAOB
15 aromatic amino acid family metabolic process GO:0009072 9.46 TPH1 TH PAH HPD
16 dihydrobiopterin metabolic process GO:0051066 9.37 QDPR GCH1
17 oxidation-reduction process GO:0055114 9.36 TPH1 TH QDPR PCBD1 PAH MTHFR
18 tetrahydrobiopterin biosynthetic process GO:0006729 9.26 QDPR PTS PCBD1 GCH1

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 9.73 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, 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
7 oxidoreductase activity GO:0016491 9.32 TPH1 TH QDPR PAH MTHFR MAOB
8 phenylalanine 4-monooxygenase activity GO:0004505 9.26 PCBD1 PAH
Sources

Sources for Phenylketonuria

About this section
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 05-Mar-2021)
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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