HPABH4A
MCID: HYP331
MIFTS: 48

Hyperphenylalaninemia, Bh4-Deficient, a (HPABH4A)

Categories: Cancer diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hyperphenylalaninemia, Bh4-Deficient, a

MalaCards integrated aliases for Hyperphenylalaninemia, Bh4-Deficient, a:

Name: Hyperphenylalaninemia, Bh4-Deficient, a 57 72 13
6-Pyruvoyl-Tetrahydropterin Synthase Deficiency 57 12 73 20 58 72 44 70
Bh4-Deficient Hyperphenylalaninemia a 12 29 6 15
Pts Deficiency 57 12 20 72
Hpabh4a 57 12 72
Hyperphenylalaninemia Due to 6-Pyruvoyltetrahydropterin Synthase Deficiency 12 58
Hyperphenylalaninemia Due to 6-Pyruvoyl-Tetrahydropterin Synthase Deficiency 20
Hyperphenylalaninemia, Tetrahydrobiopterin-Deficient, Due to Pts Deficiency 57
Hyperphenylalaninemia Tetrahydrobiopterin-Deficient Due to Pts Deficiency 72
Tetrahydobioperin-Deficient Hyperphenylalaninemia Due to Pts Deficiency 12
6-Pyruvoyltetrahydropterin Synthase Deficiency 73
Hyperphenylalaninemia, Bh4-Deficient, Type a 39
Hyperphenylalanemia, Bh4-Deficient, a 20

Characteristics:

Orphanet epidemiological data:

58
6-pyruvoyl-tetrahydropterin synthase deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
defect in tetrahydrobiopterin (bh4) synthesis
progressive neurologic deterioration if untreated
diurnal fluctuation of neurologic symptoms
treatment with bh4 is effective
neurotransmitter treatment with l-dopa and serotonin or precursors is effective
early treatment can reduce neurologic symptoms
onset in infancy (average 4 months, but may be earlier)
variable severity, ranging from central severe to peripheral to transient
prevalence in caucasians is 1 in 1,000,000
prevalence in taiwan is 1 in 132,000


HPO:

31
hyperphenylalaninemia, bh4-deficient, a:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Hyperphenylalaninemia, Bh4-Deficient, a

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 13 Definition 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. Not only does tetrahydrobiopterin deficiency cause hyperphenylalaninemia, it is also responsible for defective neurotransmission of monoamines because of malfunctioning tyrosine and tryptophan hydroxylases, both tetrahydrobiopterin-dependent hydroxylases. Clinical description When left untreated, the deficiency causes neurological signs at age 4 or 5 months, although clinical signs are often obvious from birth. The principal symptoms include psychomotor retardation, tonus disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation and difficulty swallowing. Diagnostic methods PTPS deficiency should be suspected in all infants with a positive neonatal screening test for phenylketonuria, especially when hyperphenylalaninemia is moderate. The most effective way to diagnose the disorder is to measure pteridine levels in urine and to confirm the result by measuring neurotransmitters 5-hydroxyindolacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid and with an oral tetrahydrobiopterin-loading test (20 mg/kg). Genetic counseling PTPS deficiency is an autosomal recessive genetic disorder. Management and treatment Treatment attempts to bring phenylalaninemia levels back to normal (diet with restricted phenylalanine intake or prescription of tetrahydrobiopterin) and to restore normal monoaminergic neurotransmission by administering precursors (L-dopa/carbidopa and 5-hydroxytryptophan).

MalaCards based summary : Hyperphenylalaninemia, Bh4-Deficient, a, also known as 6-pyruvoyl-tetrahydropterin synthase deficiency, is related to dystonia, dopa-responsive, due to sepiapterin reductase deficiency and hyperphenylalaninemia, and has symptoms including seizures, ataxia and tremor. An important gene associated with Hyperphenylalaninemia, Bh4-Deficient, a is PTS (6-Pyruvoyltetrahydropterin Synthase), and among its related pathways/superpathways are Metabolism and Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism. Affiliated tissues include brain and liver, and related phenotypes are opisthotonus and hypotonia

Disease Ontology : 12 An amino acid metabolic disorder that is characterized by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits that has material basis in autosomal recessive inheritance of mutation in the gene encoding 6-pyruvoyl-tetrahydropterin synthase (PTS) on chromosome 11q23.1.

OMIM® : 57 Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) comprises a genetically heterogeneous group of progressive neurologic disorders caused by autosomal recessive mutations in the genes encoding enzymes involved in the synthesis or regeneration of BH4. BH4 is a cofactor for phenylalanine hydroxylase (PAH; 612349), tyrosine hydroxylase (TH; 191290) and tryptophan hydroxylase (TPH1; 191060), the latter 2 of which are involved in neurotransmitter synthesis. The BH4-deficient HPAs are characterized phenotypically by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits (Dudesek et al., 2001). HPABH4A, caused by mutations in the PTS gene, represents the most common cause of BH4-deficient hyperphenylalaninemia (Dudesek et al., 2001). Other forms of BH4-deficient HPA include HPABH4B (233910), caused by mutation in the GCH1 gene (600225), HPABH4C (261630), caused by mutation in the QDPR gene (612676), and HPABH4D (264070), caused by mutation in the PCBD1 gene (126090). Niederwieser et al. (1982) noted that about 1 to 3% of patients with hyperphenylalaninemia have one of these BH4-deficient forms. These disorders are clinically and genetically distinct from classic phenylketonuria (PKU; 261600), caused by mutation in the PAH gene. Two additional disorders associated with BH4 deficiency and neurologic symptoms do not have overt hyperphenylalaninemia as a feature: dopa-responsive dystonia (612716), caused by mutation in the SPR gene (182125), and autosomal dominant dopa-responsive dystonia (DYT5; 128230), caused by mutation in the GCH1 gene. Patients with these disorders may develop hyperphenylalaninemia when stressed. (261640) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Hyperphenylalaninemia, BH4-deficient, A: An autosomal recessive disorder characterized by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits. Neurological symptoms are unresponsive to the classic phenylalanine-low diet.

Wikipedia : 73 6-Pyruvoyltetrahydropterin synthase deficiency is an autosomal recessive disorder that causes malignant... more...

Related Diseases for Hyperphenylalaninemia, Bh4-Deficient, a

Diseases in the Hyperphenylalaninemia, Bh4-Deficient, B family:

Hyperphenylalaninemia, Bh4-Deficient, C Hyperphenylalaninemia, Bh4-Deficient, a
Hyperphenylalaninemia, Bh4-Deficient, D

Diseases related to Hyperphenylalaninemia, Bh4-Deficient, a via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 33)
# Related Disease Score Top Affiliating Genes
1 dystonia, dopa-responsive, due to sepiapterin reductase deficiency 30.8 SPR QDPR PCBD1 GCH1
2 hyperphenylalaninemia 30.3 SPR QDPR PTS PCBD1 PAH GCH1
3 classic phenylketonuria 30.2 QDPR PTS PAH
4 phenylketonuria 30.2 QDPR PTS PCBD1 PAH GCH1
5 tetrahydrobiopterin deficiency 30.2 SPR QDPR PTS PCBD1 PAH GCH1
6 mild hyperphenylalaninemia 30.2 QDPR PTS PCBD1 PAH
7 dystonia 29.9 SPR QDPR PTS PCBD1 PAH GCH1
8 hyperphenylalaninemia, bh4-deficient, d 10.9
9 segawa syndrome, autosomal recessive 10.5
10 lymphatic malformation 5 10.3
11 schizencephaly 10.3
12 hyperprolactinemia 10.3
13 hemiplegia 10.3
14 gestational diabetes 10.3
15 vaginitis 10.3
16 hereditary dystonia 10.3
17 absence of septum pellucidum 10.3
18 hypotonia 10.3
19 autosomal recessive disease 10.2
20 dystonia, dopa-responsive 10.1 SPR GCH1
21 hemidystonia 10.0 SPR GCH1
22 oculogyric crisis 10.0 SPR GCH1
23 multifocal dystonia 10.0 SPR GCH1
24 argininemia 10.0 QDPR PAH
25 pyridoxamine 5-prime-phosphate oxidase deficiency 10.0 SPR QDPR
26 cervical dystonia 10.0 SPR GCH1
27 tyrosinemia 10.0 QDPR PTS PAH
28 hyperphenylalaninemia, bh4-deficient, b 10.0 QDPR PTS GCH1
29 vitiligo-associated multiple autoimmune disease susceptibility 1 9.9 PCBD1 PAH
30 abdominal obesity-metabolic syndrome 1 9.9 PTS PAH
31 alkaptonuria 9.8 PAH MOCS1
32 aromatic l-amino acid decarboxylase deficiency 9.7 SPR QDPR PTS GCH1
33 parkinson disease, late-onset 9.6 SPR QDPR PAH GCH1

Graphical network of the top 20 diseases related to Hyperphenylalaninemia, Bh4-Deficient, a:



Diseases related to Hyperphenylalaninemia, Bh4-Deficient, a

Symptoms & Phenotypes for Hyperphenylalaninemia, Bh4-Deficient, a

Human phenotypes related to Hyperphenylalaninemia, Bh4-Deficient, a:

58 31 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 opisthotonus 58 31 frequent (33%) Frequent (79-30%) HP:0002179
2 hypotonia 31 frequent (33%) HP:0001252
3 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
4 clonus 58 31 occasional (7.5%) Occasional (29-5%) HP:0002169
5 ptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000508
6 depressivity 58 31 occasional (7.5%) Occasional (29-5%) HP:0000716
7 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
8 dysphagia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002015
9 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001263
10 delayed speech and language development 58 31 occasional (7.5%) Occasional (29-5%) HP:0000750
11 myoclonus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001336
12 pallor 58 31 occasional (7.5%) Occasional (29-5%) HP:0000980
13 motor delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001270
14 poor head control 58 31 occasional (7.5%) Occasional (29-5%) HP:0002421
15 rigidity 58 31 occasional (7.5%) Occasional (29-5%) HP:0002063
16 choreoathetosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001266
17 excessive salivation 58 31 occasional (7.5%) Occasional (29-5%) HP:0003781
18 drowsiness 58 31 occasional (7.5%) Occasional (29-5%) HP:0002329
19 hypsarrhythmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002521
20 agitation 58 31 occasional (7.5%) Occasional (29-5%) HP:0000713
21 bradykinesia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002067
22 hyperkinetic movements 58 31 occasional (7.5%) Occasional (29-5%) HP:0002487
23 falls 58 31 occasional (7.5%) Occasional (29-5%) HP:0002527
24 oculogyric crisis 58 31 occasional (7.5%) Occasional (29-5%) HP:0010553
25 seizure 31 occasional (7.5%) HP:0001250
26 hyperreflexia 58 31 Occasional (29-5%) HP:0001347
27 hypertonia 58 31 Occasional (29-5%) HP:0001276
28 dystonia 58 31 Occasional (29-5%) HP:0001332
29 seizures 58 Occasional (29-5%)
30 tremor 31 HP:0001337
31 muscular hypotonia 58 Frequent (79-30%)
32 chorea 58 Occasional (29-5%)
33 microcephaly 31 HP:0000252
34 irritability 31 HP:0000737
35 intellectual disability, progressive 31 HP:0006887
36 abnormality of extrapyramidal motor function 58 Occasional (29-5%)
37 restlessness 58 Occasional (29-5%)
38 psychomotor retardation 31 HP:0025356
39 poor suck 31 HP:0002033
40 small for gestational age 31 HP:0001518
41 progressive neurologic deterioration 31 HP:0002344
42 recurrent fever 31 HP:0001954
43 muscular hypotonia of the trunk 31 HP:0008936
44 excessive daytime somnolence 31 HP:0001262
45 parkinsonism 31 HP:0001300
46 hyperphenylalaninemia 31 HP:0004923

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
hyperreflexia
ataxia
tremor
dystonia
more
Neurologic Behavioral Psychiatric Manifestations:
irritability

Laboratory Abnormalities:
hyperphenylalaninemia
decreased homovanillic acid (hva) and 5-hydroxyindoleacetic acid (5hiaa) in csf
increased neopterin in urine and csf
decreased or absent pts activity

Abdomen Gastrointestinal:
swallowing difficulties
poor sucking

Head And Neck Eyes:
oculogyric crises

Head And Neck Head:
microcephaly

Growth Other:
small for gestational age
poor feeding in infancy

Metabolic Features:
hyperthermia, episodic

Head And Neck Mouth:
hypersalivation

Clinical features from OMIM®:

261640 (Updated 05-Apr-2021)

UMLS symptoms related to Hyperphenylalaninemia, Bh4-Deficient, a:


seizures; ataxia; tremor; abnormality of extrapyramidal motor function; bradykinesia; muscle rigidity; stiffness

MGI Mouse Phenotypes related to Hyperphenylalaninemia, Bh4-Deficient, a:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.23 GCH1 GJB2 PAH PCBD1 POLB PTS

Drugs & Therapeutics for Hyperphenylalaninemia, Bh4-Deficient, a

Search Clinical Trials , NIH Clinical Center for Hyperphenylalaninemia, Bh4-Deficient, a

Cochrane evidence based reviews: 6-pyruvoyl-tetrahydropterin synthase deficiency

Genetic Tests for Hyperphenylalaninemia, Bh4-Deficient, a

Genetic tests related to Hyperphenylalaninemia, Bh4-Deficient, a:

# Genetic test Affiliating Genes
1 Bh4-Deficient Hyperphenylalaninemia a 29 PTS

Anatomical Context for Hyperphenylalaninemia, Bh4-Deficient, a

MalaCards organs/tissues related to Hyperphenylalaninemia, Bh4-Deficient, a:

40
Brain, Liver

Publications for Hyperphenylalaninemia, Bh4-Deficient, a

Articles related to Hyperphenylalaninemia, Bh4-Deficient, a:

(show top 50) (show all 99)
# Title Authors PMID Year
1
Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency. 6 57 61
11388593 2001
2
Identification of mutations causing 6-pyruvoyl-tetrahydropterin synthase deficiency in four Italian families. 61 57 6
9222757 1997
3
"Peripheral" tetrahydrobiopterin deficiency with hyperphenylalaninaemia due to incomplete 6-pyruvoyl tetrahydropterin synthase deficiency or heterozygosity. 61 57 6
3297709 1987
4
Treatment and outcome of Taiwanese patients with 6-pyruvoyltetrahydropterin synthase gene mutations. 57 6
11916314 2001
5
Mutation analysis of the 6-pyruvoyl-tetrahydropterin synthase gene in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency. 57 6
9450907 1998
6
Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase. 57 6
8178819 1994
7
Phenotypic variability, neurological outcome and genetics background of 6-pyruvoyl-tetrahydropterin synthase deficiency. 61 6
20059486 2010
8
[Detection of the prevalent mutations of 6-pyruvoyl-tetrahydropterin synthase gene by PCR-RFLP analysis in Chinese patients]. 6 61
17160954 2006
9
Long-term follow-up of Chinese patients who received delayed treatment for 6-pyruvoyl-tetrahydropterin synthase deficiency. 61 57
16364672 2006
10
Molecular characterization of 6-pyruvoyl-tetrahydropterin synthase deficiency in Japanese patients. 61 6
10319579 1999
11
Mutation spectrum of hyperphenylalaninemia candidate genes and the genotype-phenotype correlation in the Chinese population. 6
29499199 2018
12
Validation of copy number variation analysis for next-generation sequencing diagnostics. 6
28378820 2017
13
Four Years of Diagnostic Challenges with Tetrahydrobiopterin Deficiencies in Iranian Patients. 6
27246466 2017
14
Thirteen year retrospective review of the spectrum of inborn errors of metabolism presenting in a tertiary center in Saudi Arabia. 6
27629047 2016
15
Targeted Next Generation Sequencing in Patients with Inborn Errors of Metabolism. 6
27243974 2016
16
Diagnosis, treatment and follow-up of patients with tetrahydrobiopterin deficiency in Shandong province, China. 6
25304915 2015
17
Tetrahydrobiopterin deficiency among Serbian patients presenting with hyperphenylalaninemia. 6
25418970 2015
18
Prevalence of inherited neurotransmitter disorders in patients with movement disorders and epilepsy: a retrospective cohort study. 6
25758715 2015
19
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. 6
25525159 2015
20
Fast clinical molecular diagnosis of hyperphenylalaninemia using next-generation sequencing-based on a custom AmpliSeqâ„¢ panel and Ion Torrent PGM sequencing. 6
25456745 2014
21
Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results. 6
25087612 2014
22
Accurate molecular diagnosis of phenylketonuria and tetrahydrobiopterin-deficient hyperphenylalaninemias using high-throughput targeted sequencing. 6
23942198 2014
23
The Molecular Bases of Phenylketonuria (PKU) in New South Wales, Australia: Mutation Profile and Correlation with Tetrahydrobiopterin (BH4) Responsiveness. 6
24368688 2014
24
Demographics, diagnosis and treatment of 256 patients with tetrahydrobiopterin deficiency in mainland China: results of a retrospective, multicentre study. 6
23138986 2013
25
Tetrahydrobiopterin responsiveness in phenylketonuria: prediction with the 48-hour loading test and genotype. 6
23842451 2013
26
Molecular epidemiology and BH4-responsiveness in patients with phenylalanine hydroxylase deficiency from Galicia region of Spain. 6
23500595 2013
27
Splicing of phenylalanine hydroxylase (PAH) exon 11 is vulnerable: molecular pathology of mutations in PAH exon 11. 6
22698810 2012
28
Mutation spectrum of and founder effects affecting the PTS gene in East Asian populations. 6
22237589 2012
29
Protein stability and in vivo concentration of missense mutations in phenylalanine hydroxylase. 6
21953985 2012
30
Phenylketonuria in Hong Kong Chinese: a call for hyperphenylalaninemia newborn screening in the Special Administrative Region, China. 6
21933604 2011
31
Disease-causing mutations improving the branch site and polypyrimidine tract: pseudoexon activation of LINE-2 and antisense Alu lacking the poly(T)-tail. 6
19280650 2009
32
[Mutational analysis of patients with 6-pyruvoyltetrahydrobiopterin synthesis deficiency]. 6
19350512 2009
33
A mutation analysis of the phenylalanine hydroxylase (PAH) gene in the Israeli population. 6
18294361 2008
34
[Mutation analysis and one novel mutation detection of 6-pyruvoyl tetrahydropterin synthase gene in children with tetrahydrobiopterin deficiency]. 6
18505119 2008
35
Molecular genetics of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. 6
17935162 2008
36
Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase. 6
16917893 2006
37
6-pyruvoyltetrahydropterin synthase deficiency two-case report. 6
16850690 2006
38
Long-term treatment with tetrahydrobiopterin increases phenylalanine tolerance in children with severe phenotype of phenylketonuria. 6
16051511 2005
39
PAH gene mutations in the Sicilian population: association with minihaplotypes and expression analysis. 6
11708866 2001
40
Catecholamines and serotonin are differently regulated by tetrahydrobiopterin. A study from 6-pyruvoyltetrahydropterin synthase knockout mice. 57
11517215 2001
41
Tetrahydrobiopterin-deficient hyperphenylalaninemia in the Chinese. 6
11694255 2001
42
Identification of three novel 6-pyruvoyl-tetrahydropterin synthase gene mutations (226C>T, IVS3+1G>A, 116-119delTGTT) in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency. 6
11438997 2001
43
Isolated central form of tetrahydrobiopterin deficiency associated with hemizygosity on chromosome 11q and a mutant allele of PTPS. 6
10874306 2000
44
Single-step mutation scanning of the 6-pyruvoyltetrahydropterin synthase gene in patients with hyperphenylalaninemia. 6
10585341 1999
45
A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype. 6
9634518 1998
46
Mutations in the GTP cyclohydrolase I and 6-pyruvoyl-tetrahydropterin synthase genes. 57
9222755 1997
47
Mutations of the phenylalanine hydroxylase gene in mild hyperphenylalaninemia: a novel mutation in exon 3. 6
9298832 1997
48
Identification of a common 6-pyruvoyl-tetrahydropterin synthase mutation at codon 87 in Chinese phenylketonuria caused by tetrahydrobiopterin synthesis deficiency. 6
8707300 1996
49
Phenylketonuria mutation analysis in Northern Ireland: a rapid stepwise approach. 6
8533759 1995
50
Structural and functional consequences of mutations in 6-pyruvoyltetrahydropterin synthase causing hyperphenylalaninemia in humans. Phosphorylation is a requirement for in vivo activity. 6
7493990 1995

Variations for Hyperphenylalaninemia, Bh4-Deficient, a

ClinVar genetic disease variations for Hyperphenylalaninemia, Bh4-Deficient, a:

6 (show top 50) (show all 84)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PTS NM_000317.3(PTS):c.74G>A (p.Arg25Gln) SNV Pathogenic 476 rs104894273 GRCh37: 11:112097240-112097240
GRCh38: 11:112226517-112226517
2 PTS NM_000317.3(PTS):c.155A>G (p.Asn52Ser) SNV Pathogenic 479 rs104894275 GRCh37: 11:112099388-112099388
GRCh38: 11:112228665-112228665
3 PTS NM_000317.3(PTS):c.259C>T (p.Pro87Ser) SNV Pathogenic 480 rs104894276 GRCh37: 11:112103901-112103901
GRCh38: 11:112233178-112233178
4 PTS NM_000317.3(PTS):c.286G>A (p.Asp96Asn) SNV Pathogenic 484 rs104894280 GRCh37: 11:112103928-112103928
GRCh38: 11:112233205-112233205
5 PTS NM_000317.3(PTS):c.163+696_163+750del Deletion Pathogenic 485 rs1555198165 GRCh37: 11:112100090-112100144
GRCh38: 11:112229367-112229421
6 PTS NM_000317.3(PTS):c.84-323A>T SNV Pathogenic 486 rs794726657 GRCh37: 11:112098994-112098994
GRCh38: 11:112228271-112228271
7 PTS NM_000317.3(PTS):c.73C>G (p.Arg25Gly) SNV Pathogenic 463153 rs1167104933 GRCh37: 11:112097239-112097239
GRCh38: 11:112226516-112226516
8 PTS NM_000317.3(PTS):c.200C>T (p.Thr67Met) SNV Pathogenic 463151 rs370340361 GRCh37: 11:112101362-112101362
GRCh38: 11:112230639-112230639
9 PTS NM_000317.3(PTS):c.159T>G (p.Tyr53Ter) SNV Pathogenic 638994 rs781197929 GRCh37: 11:112099392-112099392
GRCh38: 11:112228669-112228669
10 PTS NM_000317.3(PTS):c.84-291A>G SNV Pathogenic 649292 rs1480995114 GRCh37: 11:112099026-112099026
GRCh38: 11:112228303-112228303
11 PTS NM_000317.3(PTS):c.272A>G (p.Lys91Arg) SNV Pathogenic 813419 rs761285716 GRCh37: 11:112103914-112103914
GRCh38: 11:112233191-112233191
12 PTS NC_000011.10:g.(?_112226444)_(112233555_?)del Deletion Pathogenic 831225 GRCh37: 11:112097167-112104278
GRCh38:
13 PTS NC_000011.10:g.(?_112226434)_(112226536_?)del Deletion Pathogenic 832307 GRCh37: 11:112097157-112097259
GRCh38:
14 PTS NM_000317.3(PTS):c.73C>T (p.Arg25Ter) SNV Pathogenic 859996 GRCh37: 11:112097239-112097239
GRCh38: 11:112226516-112226516
15 PTS NM_000317.3(PTS):c.107del (p.Asn36fs) Deletion Pathogenic 941033 GRCh37: 11:112099337-112099337
GRCh38: 11:112228614-112228614
16 PAH NM_000277.3(PAH):c.631C>A (p.Pro211Thr) SNV Pathogenic 102766 rs62514931 GRCh37: 12:103248989-103248989
GRCh38: 12:102855211-102855211
17 PAH NM_000277.3(PAH):c.527G>T (p.Arg176Leu) SNV Pathogenic 631 rs74486803 GRCh37: 12:103249093-103249093
GRCh38: 12:102855315-102855315
18 PTS NM_000317.3(PTS):c.118_121del (p.Phe40fs) Deletion Pathogenic 550850 rs747260038 GRCh37: 11:112099349-112099352
GRCh38: 11:112228626-112228629
19 PAH NM_000277.3(PAH):c.1139C>T (p.Thr380Met) SNV Pathogenic 628 rs62642937 GRCh37: 12:103237484-103237484
GRCh38: 12:102843706-102843706
20 PTS NM_000317.3(PTS):c.238A>G (p.Met80Val) SNV Pathogenic/Likely pathogenic 372484 rs1057517810 GRCh37: 11:112101400-112101400
GRCh38: 11:112230677-112230677
21 PTS NM_000317.3(PTS):c.297C>A (p.Tyr99Ter) SNV Pathogenic/Likely pathogenic 370413 rs145882709 GRCh37: 11:112103939-112103939
GRCh38: 11:112233216-112233216
22 PTS NM_000317.3(PTS):c.317C>T (p.Thr106Met) SNV Pathogenic/Likely pathogenic 552175 rs200712908 GRCh37: 11:112104157-112104157
GRCh38: 11:112233434-112233434
23 PTS NM_000317.3(PTS):c.84-3C>G SNV Pathogenic/Likely pathogenic 553378 rs1230781262 GRCh37: 11:112099314-112099314
GRCh38: 11:112228591-112228591
24 PTS NM_000317.3(PTS):c.260C>T (p.Pro87Leu) SNV Pathogenic/Likely pathogenic 553829 rs765406631 GRCh37: 11:112103902-112103902
GRCh38: 11:112233179-112233179
25 PTS NM_000317.3(PTS):c.166G>A (p.Val56Met) SNV Pathogenic/Likely pathogenic 481 rs104894277 GRCh37: 11:112100933-112100933
GRCh38: 11:112230210-112230210
26 PTS NM_000317.3(PTS):c.393del (p.Val132fs) Deletion Pathogenic/Likely pathogenic 556173 rs780332520 GRCh37: 11:112104230-112104230
GRCh38: 11:112233507-112233507
27 PTS NM_000317.3(PTS):c.243_243+1dup Duplication Likely pathogenic 554248 rs866922524 GRCh37: 11:112101404-112101405
GRCh38: 11:112230681-112230682
28 PTS NM_000317.3(PTS):c.315-1G>C SNV Likely pathogenic 554579 rs776543880 GRCh37: 11:112104154-112104154
GRCh38: 11:112233431-112233431
29 PTS NM_000317.3(PTS):c.166_168GTG[1] (p.Val57del) Microsatellite Likely pathogenic 551630 rs770387277 GRCh37: 11:112100933-112100935
GRCh38: 11:112230210-112230212
30 PTS NM_000317.3(PTS):c.164-2A>G SNV Likely pathogenic 553634 rs1555198233 GRCh37: 11:112100929-112100929
GRCh38: 11:112230206-112230206
31 PTS NM_000317.3(PTS):c.225_226TC[1] (p.Leu76fs) Microsatellite Likely pathogenic 553847 rs1555198263 GRCh37: 11:112101387-112101388
GRCh38: 11:112230664-112230665
32 GCH1 NM_000161.3(GCH1):c.274C>A (p.Leu92Ile) SNV Likely pathogenic 522898 rs763294577 GRCh37: 14:55369108-55369108
GRCh38: 14:54902390-54902390
33 PTS NM_000317.3(PTS):c.337del (p.Tyr113fs) Deletion Likely pathogenic 551176 rs1555198494 GRCh37: 11:112104175-112104175
GRCh38: 11:112233452-112233452
34 PTS NM_000317.3(PTS):c.244-1G>T SNV Likely pathogenic 551511 rs1555198451 GRCh37: 11:112103885-112103885
GRCh38: 11:112233162-112233162
35 PTS NM_000317.3(PTS):c.2T>G (p.Met1Arg) SNV Likely pathogenic 982126 GRCh37: 11:112097168-112097168
GRCh38: 11:112226445-112226445
36 PTS NM_000317.3(PTS):c.342C>G (p.Ile114Met) SNV Likely pathogenic 982127 GRCh37: 11:112104182-112104182
GRCh38: 11:112233459-112233459
37 PTS NM_000317.3(PTS):c.315-2A>G SNV Likely pathogenic 558308 rs1555198483 GRCh37: 11:112104153-112104153
GRCh38: 11:112233430-112233430
38 PTS NM_000317.3(PTS):c.407A>G (p.Asp136Gly) SNV Likely pathogenic 862227 GRCh37: 11:112104247-112104247
GRCh38: 11:112233524-112233524
39 PTS NM_000317.3(PTS):c.186+1G>T SNV Likely pathogenic 556264 rs1256819927 GRCh37: 11:112100954-112100954
GRCh38: 11:112230231-112230231
40 PTS NM_000317.3(PTS):c.314+1G>C SNV Likely pathogenic 557025 rs1555198462 GRCh37: 11:112103957-112103957
GRCh38: 11:112233234-112233234
41 PTS NM_000317.3(PTS):c.347A>G (p.Asp116Gly) SNV Likely pathogenic 483 rs104894279 GRCh37: 11:112104187-112104187
GRCh38: 11:112233464-112233464
42 PTS NM_000317.3(PTS):c.132C>T (p.Asn44=) SNV Conflicting interpretations of pathogenicity 302497 rs763556416 GRCh37: 11:112099365-112099365
GRCh38: 11:112228642-112228642
43 PTS NM_000317.3(PTS):c.83+1G>A SNV Conflicting interpretations of pathogenicity 552817 rs927103678 GRCh37: 11:112097250-112097250
GRCh38: 11:112226527-112226527
44 PTS NM_000317.3(PTS):c.370G>T (p.Val124Leu) SNV Conflicting interpretations of pathogenicity 556231 rs150726932 GRCh37: 11:112104210-112104210
GRCh38: 11:112233487-112233487
45 PTS NM_000317.3(PTS):c.402A>C (p.Glu134Asp) SNV Uncertain significance 550683 rs746993982 GRCh37: 11:112104242-112104242
GRCh38: 11:112233519-112233519
46 PTS NM_000317.3(PTS):c.400G>A (p.Glu134Lys) SNV Uncertain significance 556230 rs779681799 GRCh37: 11:112104240-112104240
GRCh38: 11:112233517-112233517
47 PTS NM_000317.3(PTS):c.289G>A (p.Val97Met) SNV Uncertain significance 555095 rs750455879 GRCh37: 11:112103931-112103931
GRCh38: 11:112233208-112233208
48 PTS NM_000317.3(PTS):c.400G>T (p.Glu134Ter) SNV Uncertain significance 555399 rs779681799 GRCh37: 11:112104240-112104240
GRCh38: 11:112233517-112233517
49 PTS NM_000317.3(PTS):c.108C>G (p.Asn36Lys) SNV Uncertain significance 555429 rs1449216377 GRCh37: 11:112099341-112099341
GRCh38: 11:112228618-112228618
50 PTS NM_000317.3(PTS):c.338A>G (p.Tyr113Cys) SNV Uncertain significance 553103 rs762894736 GRCh37: 11:112104178-112104178
GRCh38: 11:112233455-112233455

UniProtKB/Swiss-Prot genetic disease variations for Hyperphenylalaninemia, Bh4-Deficient, a:

72 (show all 24)
# Symbol AA change Variation ID SNP ID
1 PTS p.Arg16Cys VAR_006816 rs104894274
2 PTS p.Arg25Gly VAR_006817 rs116710493
3 PTS p.Arg25Gln VAR_006818 rs104894273
4 PTS p.Glu35Gly VAR_006819 rs132832099
5 PTS p.Asn36Lys VAR_006820 rs144921637
6 PTS p.Asn52Ser VAR_006821 rs104894275
7 PTS p.Val56Met VAR_006822 rs104894277
8 PTS p.Thr67Met VAR_006824 rs370340361
9 PTS p.Val70Asp VAR_006825
10 PTS p.Pro87Leu VAR_006826 rs765406631
11 PTS p.Pro87Ser VAR_006827 rs104894276
12 PTS p.Asp96Asn VAR_006828 rs104894280
13 PTS p.Phe100Val VAR_006829
14 PTS p.Thr106Met VAR_006830 rs200712908
15 PTS p.Ile114Val VAR_006831 rs155519849
16 PTS p.Lys129Glu VAR_006832 rs104044182
17 PTS p.Asp136Val VAR_006833
18 PTS p.Asn47Asp VAR_008040 rs104894278
19 PTS p.Asp116Gly VAR_008041 rs104894279
20 PTS p.Leu26Phe VAR_058265 rs131723062
21 PTS p.Val97Met VAR_058266 rs750455879
22 PTS p.Tyr99Cys VAR_058267 rs155519845
23 PTS p.Val124Leu VAR_058268 rs150726932
24 PTS p.Asp136Gly VAR_058269

Expression for Hyperphenylalaninemia, Bh4-Deficient, a

Search GEO for disease gene expression data for Hyperphenylalaninemia, Bh4-Deficient, a.

Pathways for Hyperphenylalaninemia, Bh4-Deficient, a

GO Terms for Hyperphenylalaninemia, Bh4-Deficient, a

Cellular components related to Hyperphenylalaninemia, Bh4-Deficient, a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.23 SPR QDPR PTS PCBD1 PAH MOCS1

Biological processes related to Hyperphenylalaninemia, Bh4-Deficient, a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.67 SPR QDPR PCBD1 PAH
2 cellular amino acid metabolic process GO:0006520 9.32 QDPR PTS
3 nitric oxide biosynthetic process GO:0006809 9.26 SPR GCH1
4 dihydrobiopterin metabolic process GO:0051066 9.16 QDPR GCH1
5 L-phenylalanine catabolic process GO:0006559 9.13 QDPR PCBD1 PAH
6 tetrahydrobiopterin biosynthetic process GO:0006729 9.02 SPR QDPR PTS PCBD1 GCH1

Molecular functions related to Hyperphenylalaninemia, Bh4-Deficient, a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 identical protein binding GO:0042802 9.55 QDPR PTS PCBD1 GJB2 GCH1
2 phenylalanine 4-monooxygenase activity GO:0004505 8.96 PCBD1 PAH
3 lyase activity GO:0016829 8.92 PTS POLB PCBD1 MOCS1

Sources for Hyperphenylalaninemia, Bh4-Deficient, a

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
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45 MESH via Orphanet
46 MGI
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50 NCIt
51 NDF-RT
53 NINDS
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56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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