PAH phenylalanine hydroxylase [Homo sapiens (human)] - Gene

Summary

Go to the top of the page Help

Official Symbol: PAHprovided by HGNC
Official Full Name: phenylalanine hydroxylaseprovided by HGNC
Primary source: HGNC:8582
See related: Ensembl:ENSG00000171759; HPRD:08943; MIM:612349; Vega:OTTHUMG00000169966
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PH; PKU; PKU1
Summary: PAH encodes the enzyme phenylalanine hydroxylase that is the rate-limiting step in phenylalanine catabolism. Deficiency of this enzyme activity results in the autosomal recessive disorder phenylketonuria. [provided by RefSeq, Jul 2008]

Genomic context

Go to the top of the page Help

Location :: 12q22-q24.2

Sequence :: Chromosome: 12; NC_000012.11 (103232104..103311381, complement)

See PAH in Epigenomics, MapViewer

Chromosome 12 - NC_000012.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions What's a GeneRIF?

A new model for allosteric regulation of phenylalanine hydroxylase: implications for disease and therapeutics.
Title: A new model for allosteric regulation of phenylalanine hydroxylase: implications for disease and therapeutics.
Thirteen different mutations were identified in the PAH gene in Lebanese patients with phenylalanine hydroxylase deficiency.
Title: Spectrum of mutations in Lebanese patients with phenylalanine hydroxylase deficiency.
The p.G352fsdelG mutation in the PAH gene does not appear to be prevalent in the Moroccan population and would be responsible for only few cases of phenylketonuria.
Title: Low prevalence of p.G352fsdelG mutation in phenylketonuria patients from Morocco.
PAH exon 11 is vulnerable due to a weak 3' splice site.
Title: Splicing of phenylalanine hydroxylase (PAH) exon 11 is vulnerable: molecular pathology of mutations in PAH exon 11.
Phenylketonuria (PKU) associated multiple mutations in phenylalanine hydroxylase (PAH) gene were identified in Balto-Russian population studied.
Title: [Mutation analysis of the phenylalanine hydroxylase gene of phenylketonuria patients of Kemerovskaya Oblast' and Saha Republic].
Eleven different mutations were found, with the most frequent mutation, IVS10-11G>A, accounting for 19% of Khorasan-Razavi PKU alleles.
Title: Mutation spectrum of the PAH gene in the PKU patients from Khorasan Razavi province of Iran.
Disease-causing mutations were identified on 209 alleles of the phenylalanine hydroxylase gene.
Title: Five novel mutations and two large deletions in a population analysis of the phenylalanine hydroxylase gene.
The mutations of phenylketonuria patients from Hebei Province are scattered throughout the PAH gene. Most of them are of single nucleotide substitutions, but large deletions are not rare.
Title: [Mutation analysis of phenylalanine hydroxylase gene in 55 patients with phenylketonuria from Hebei province].
The spectrum of phenylalanine hydroxylase (PAH) gene mutations upon investigating 35 index patients identified with hyperphenylalaninemia in Armenia, is presented.
Title: The spectrum of phenylketonuria genotypes in the Armenian population: identification of three novel mutant PAH alleles.
mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase gene in patients with phenylketonuria
Title: [Study on the mutations of phenylalanine hydroxylase gene in patients with phenylketonuria in Shanxi province].

Submit: New GeneRIF Correction See all (88)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Phenylalanine hydroxylase (PAH) deficiency results in intolerance to the dietary intake of the essential amino acid phenylalanine and produces a spectrum of disorders including phenylketonuria (PKU), non-PKU hyperphenylalaninemia (non-PKU HPA), and variant PKU. Classic PKU is caused by a complete or near-complete deficiency of phenylalanine hydroxylase activity; without dietary restriction of phenylalanine, most children with PKU develop profound and irreversible intellectual disability. Non-PKU HPA is associated with a much lower risk of impaired cognitive development in the absence of treatment.

Diagnosis Testing

PAH deficiency can be diagnosed by newborn screening in virtually 100% of cases based on detection of the presence of hyperphenylalaninemia using the Guthrie microbial or other assays on a blood spot obtained from a heel prick. PKU is diagnosed in individuals with plasma phenylalanine (Phe) concentrations higher than 1000 micromol/L in the untreated state; non-PKU HPA is diagnosed in individuals with plasma Phe concentrations consistently above normal (i.e., >120 micromol/L), but lower than 1000 micromol/L when on a normal diet. Molecular genetic testing of PAH is used primarily for genetic counseling purposes to determine carrier status of at-risk relatives and for prenatal testing.

Genetic Counseling

PAH deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations have been identified in an affected family member.

References

PMID: 20301677

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Source	Pubs	Description
P00439	P00439	PAH	HPRD	PubMed
BioGRID:111090	BioGRID:111090	PAH	BioGRID	PubMed	Co-crystal Structure; Two-hybrid
BioGRID:111090	BioGRID:111125	PCBD1	BioGRID	PubMed	Two-hybrid
BioGRID:111090	BioGRID:111798	QDPR	BioGRID	PubMed	Two-hybrid
BioGRID:111090	BioGRID:112143	RPS24	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

Go to the top of the page Help

Abnormal metabolism in phenylketonuria, organism-specific biosystem (from REACTOME)
Abnormal metabolism in phenylketonuria, organism-specific biosystemPhenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine. In the absence of functional PAH, phenylalanine accumulates to high levels in the blood (Mitchell and Scriver 20...
Biogenic Amine Synthesis, organism-specific biosystem (from WikiPathways)
Biogenic Amine Synthesis, organism-specific biosystemBiogenic amines are one of two broad classes of classical neurotransmitters (the other being amino acids) and include: acetylcholine, serotonin, histamine, and the catecholamines epinephrine, norepin...
Biosynthesis of amino acids, organism-specific biosystem (from KEGG)
Biosynthesis of amino acids, organism-specific biosystem
Biosynthesis of amino acids
Biosynthesis of amino acids, conserved biosystem (from KEGG)
Biosynthesis of amino acids, conserved biosystem
Biosynthesis of amino acids
Disease, organism-specific biosystem (from REACTOME)
Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of amino acids and derivatives, organism-specific biosystem (from REACTOME)
Metabolism of amino acids and derivatives, organism-specific biosystemThis group of reactions is responsible for: 1) the breakdown of amino acids; 2) the synthesis of urea from ammonia and amino groups generated by amino acid breakdown; 3) the synthesis of the ten amin...
Phenylalanine and tyrosine catabolism, organism-specific biosystem (from REACTOME)
Phenylalanine and tyrosine catabolism, organism-specific biosystemThe first reaction in this pathway converts phenylalanine to tyrosine, coupled to the conversion of tetrahydrobiopterin to 4a-hydroxytetrahydrobiopterin, catalyzed by phenylalanine hydroxylase. (Defi...
Phenylalanine metabolism, organism-specific biosystem (from KEGG)
Phenylalanine metabolism, organism-specific biosystem
Phenylalanine metabolism
Phenylalanine metabolism, conserved biosystem (from KEGG)
Phenylalanine metabolism, conserved biosystem
Phenylalanine metabolism
Phenylalanine, tyrosine and tryptophan biosynthesis, organism-specific biosystem (from KEGG)
Phenylalanine, tyrosine and tryptophan biosynthesis, organism-specific biosystem
Phenylalanine, tyrosine and tryptophan biosynthesis
Phenylalanine, tyrosine and tryptophan biosynthesis, conserved biosystem (from KEGG)
Phenylalanine, tyrosine and tryptophan biosynthesis, conserved biosystem
Phenylalanine, tyrosine and tryptophan biosynthesis
SIDS Susceptibility Pathways, organism-specific biosystem (from WikiPathways)
SIDS Susceptibility Pathways, organism-specific biosystemIn this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an ov...
phenylalanine degradation I (aerobic), organism-specific biosystem (from BIOCYC)
phenylalanine degradation I (aerobic), organism-specific biosystem: PHE degradation involves its initial hydroxylation to : TYR by : CPLX-7067. This is followed by degradation of : TYR by an organism-specific pathway, such as that shown in the pathway link above. ...
phenylalanine degradation I (aerobic), conserved biosystem (from BIOCYC)
phenylalanine degradation I (aerobic), conserved biosystem|FRAME: PHE| degradation in mammals, and some fungi and bacteria, involves its initial hydroxylation to |FRAME: TYR| by |FRAME: CPLX-7067|. This is followed by degradation of |FRAME: TYR| by an orga...
tyrosine biosynthesis IV, organism-specific biosystem (from BIOCYC)
tyrosine biosynthesis IV, organism-specific biosystemIn humans, : PHE is an indispensable dietary amino acid, which may either be used for protein synthesis or converted to the amino acid : TYR, the precursor for catecholamine and thyroid hormone synt...
tyrosine biosynthesis IV, conserved biosystem (from BIOCYC)
tyrosine biosynthesis IV, conserved biosystemIn humans, |FRAME: PHE| is an indispensable amino acid, which may either be used for protein synthesis or be converted to the nonessential amino acid |FRAME: TYR|, the precursor for catecholamine and...

General gene information

Go to the top of the page Help

Markers

SHGC-143102 (e-PCR)
- UniSTS:171794

GDB:177555 (e-PCR)
- UniSTS:154928

GDB:177630 (e-PCR)
- UniSTS:154940

PAH (e-PCR), detects polymorphism
- UniSTS:266309

SHGC-155640 (e-PCR)
- UniSTS:182623

WI-12632 (e-PCR)
- UniSTS:63336

RH68979 (e-PCR)
- UniSTS:57209

GDB:178434 (e-PCR)
- UniSTS:155011

GDB:181551 (e-PCR)
- UniSTS:155277

GDB:199078 (e-PCR)
- UniSTS:156049

D12S1418 (e-PCR)
- UniSTS:72878

GDB:196577 (e-PCR)
- UniSTS:155865

SHGC-107607 (e-PCR)
- UniSTS:170458

SHGC-37493 (e-PCR)
- UniSTS:37597

GDB:182301 (e-PCR)
- UniSTS:155364

GDB:182302 (e-PCR)
- UniSTS:155365

GDB:182303 (e-PCR)
- UniSTS:155366

GDB:454047 (e-PCR)
- UniSTS:157417

GDB:454053 (e-PCR)
- UniSTS:157418

GDB:454059 (e-PCR)
- UniSTS:157419

GDB:177363 (e-PCR)
- UniSTS:154861

Genotypes

See PAH SNP Geneview Report
See PAH SNP Genotype Report
See PAH SNP Variation Viewer Report

Homology

Homologs of the PAH gene: The PAH gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and C.elegans.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
amino acid binding	IEA Inferred from Electronic Annotation more info
iron ion binding	IEA Inferred from Electronic Annotation more info
phenylalanine 4-monooxygenase activity	EXP Inferred from Experiment more info

Process	Evidence Code	Pubs
L-phenylalanine catabolic process	IEA Inferred from Electronic Annotation more info
L-phenylalanine catabolic process	TAS Traceable Author Statement more info
catecholamine biosynthetic process	NAS Non-traceable Author Statement more info	PubMed
cellular amino acid biosynthetic process	TAS Traceable Author Statement more info	PubMed
cellular nitrogen compound metabolic process	TAS Traceable Author Statement more info
neurotransmitter biosynthetic process	NAS Non-traceable Author Statement more info	PubMed
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info

General protein information

Go to the top of the page Help

Preferred Names: phenylalanine-4-hydroxylase

Names: phenylalanine-4-hydroxylase; phe-4-monooxygenase; phenylalanine 4-monooxygenase

NP_000268.1

EC 1.14.16.1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008690.1 RefSeqGene

Range

5001..84277

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000277.1 → NP_000268.1 phenylalanine-4-hydroxylase

Status: REVIEWED

Source sequence(s)

U49897

Consensus CDS

CCDS9092.1

UniProtKB/Swiss-Prot

P00439

Related

ENSP00000303500, OTTHUMP00000242536, ENST00000307000, OTTHUMT00000406693

Conserved Domains (3) summary

cd03347
Location:119 – 424
Blast Score: 1504

eu_PheOH; Eukaryotic phenylalanine-4-hydroxylase (eu_PheOH); a member of the biopterin-dependent aromatic amino acid hydroxylase family of non-heme, iron(II)-dependent enzymes that also includes prokaryotic phenylalanine-4-hydroxylase (pro_PheOH), eukaryotic ...

TIGR01268
Location:20 – 452
Blast Score: 2128

Phe4hydrox_tetr; phenylalanine-4-hydroxylase, tetrameric form

cd04931
Location:21 – 110
Blast Score: 445

ACT_PAH; ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, phenylalanine hydroxylases (PAH)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000012.11 Reference GRCh37.p10 Primary Assembly

Range

103232104..103311381, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000144.1 Alternate HuRef

Range

100291597..100370682, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018923.1 Alternate CHM1_1.0

Range

103072282..103151383, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01053223.1 (39911..118996)	None
genomic	AC069227.24 (23530..102807)	None
genomic	AF404777.1	AAL78816.1
genomic	AMYH01004704.1 (871321..950422)	None
genomic	AY722625.1	AAU11304.1
genomic	CH471054.1	EAW97700.1
		EAW97701.1
		EAW97702.1
genomic	S83538.1	AAB50813.1
mRNA	AK298419.1	BAG60644.1
mRNA	AK313383.1	BAG36181.1
mRNA	BC026251.1	AAH26251.1
mRNA	K03020.1	AAA60082.1
mRNA	L47726.1	AAA80910.1
mRNA	S61296.1	AAD13926.1
mRNA	S61396.1	AAD13928.1
mRNA	U49897.1	AAC51772.1
other-genetic	HQ447614.1	ADQ32100.1