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Aliases for PAH Gene

Aliases for PAH Gene

  • Phenylalanine Hydroxylase 2 3 5
  • Phenylalanine 4-Monooxygenase 2 3
  • Phe-4-Monooxygenase 3 4
  • EC 1.14.16.1 4 63
  • EC 1.14.16 63
  • PKU1 3
  • PKU 3
  • PH 3

External Ids for PAH Gene

Previous GeneCards Identifiers for PAH Gene

  • GC12M102330
  • GC12M103190
  • GC12M101735
  • GC12M101736
  • GC12M101737
  • GC12M100292
  • GC12M103230

Summaries for PAH Gene

Entrez Gene Summary for PAH Gene

  • 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]

GeneCards Summary for PAH Gene

PAH (Phenylalanine Hydroxylase) is a Protein Coding gene. Diseases associated with PAH include Phenylketonuria and Tetrahydrobiopterin-Responsive Hyperphenylalaninemia/Phenylketonuria. Among its related pathways are Tyrosine metabolism and Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism. GO annotations related to this gene include iron ion binding and 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. An important paralog of this gene is TPH1.

Gene Wiki entry for PAH Gene

No data available for UniProtKB/Swiss-Prot , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PAH Gene

Genomics for PAH Gene

Regulatory Elements for PAH Gene

Enhancers for PAH Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around PAH on UCSC Golden Path with GeneCards custom track

Genomic Location for PAH Gene

Chromosome:
12
Start:
102,836,885 bp from pter
End:
102,958,410 bp from pter
Size:
121,526 bases
Orientation:
Minus strand

Genomic View for PAH Gene

Genes around PAH on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PAH Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PAH Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PAH Gene

Proteins for PAH Gene

  • Protein details for PAH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P00439-PH4H_HUMAN
    Recommended name:
    Phenylalanine-4-hydroxylase
    Protein Accession:
    P00439
    Secondary Accessions:
    • Q16717
    • Q8TC14

    Protein attributes for PAH Gene

    Size:
    452 amino acids
    Molecular mass:
    51862 Da
    Cofactor:
    Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
    Quaternary structure:
    • Homodimer and homotetramer.

    Three dimensional structures from OCA and Proteopedia for PAH Gene

neXtProt entry for PAH Gene

Proteomics data for PAH Gene at MOPED

Post-translational modifications for PAH Gene

  • Phosphorylation at Ser-16 increases basal activity and facilitates activation by the substrate phenylalanine.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PAH Gene

Domains & Families for PAH Gene

Gene Families for PAH Gene

Suggested Antigen Peptide Sequences for PAH Gene

Graphical View of Domain Structure for InterPro Entry

P00439

UniProtKB/Swiss-Prot:

PH4H_HUMAN :
  • Contains 1 ACT domain.
  • Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
Domain:
  • Contains 1 ACT domain.
Family:
  • Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
genes like me logo Genes that share domains with PAH: view

Function for PAH Gene

Molecular function for PAH Gene

GENATLAS Biochemistry:
phenylalanine hydroxylase,iron containing enzyme
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=150 uM for L-Phe with BH(4) as cofactor {ECO:0000269 PubMed:18835579}; KM=30 uM for BH(4) {ECO:0000269 PubMed:18835579}; Vmax=3640 nmol/min/mg enzyme with BH(4) as cofactor (preincubated with L-Phe) {ECO:0000269 PubMed:18835579}; Vmax=1230 nmol/min/mg enzyme with BH(4) as cofactor (preincubated with BH(4)) {ECO:0000269 PubMed:18835579}; Temperature dependence: Optimum temperature is 50 degrees Celsius. {ECO:0000269 PubMed:18835579};
UniProtKB/Swiss-Prot CatalyticActivity:
L-phenylalanine + tetrahydrobiopterin + O(2) = L-tyrosine + 4a-hydroxytetrahydrobiopterin.
UniProtKB/Swiss-Prot EnzymeRegulation:
N-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine and to constitute an "inhibitory" domain that regulates the activity of a catalytic domain in the C-terminal portion of the molecule.

Enzyme Numbers (IUBMB) for PAH Gene

Gene Ontology (GO) - Molecular Function for PAH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004505 phenylalanine 4-monooxygenase activity IEA,IDA 20667834
genes like me logo Genes that share ontologies with PAH: view
genes like me logo Genes that share phenotypes with PAH: view

Human Phenotype Ontology for PAH Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

miRNA for PAH Gene

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for PAH Gene

Localization for PAH Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PAH Gene COMPARTMENTS Subcellular localization image for PAH gene
Compartment Confidence
cytosol 5
extracellular 5
plasma membrane 2
chloroplast 1
mitochondrion 1
nucleus 1

No data available for Subcellular locations from UniProtKB/Swiss-Prot and Gene Ontology (GO) - Cellular Components for PAH Gene

Pathways & Interactions for PAH Gene

genes like me logo Genes that share pathways with PAH: view

UniProtKB/Swiss-Prot P00439-PH4H_HUMAN

  • Pathway: Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 1/6.

Gene Ontology (GO) - Biological Process for PAH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008152 metabolic process IEA --
GO:0009072 aromatic amino acid family metabolic process IEA --
GO:0018126 protein hydroxylation IEA --
GO:0034641 cellular nitrogen compound metabolic process TAS --
GO:0042558 pteridine-containing compound metabolic process IEA --
genes like me logo Genes that share ontologies with PAH: view

No data available for SIGNOR curated interactions for PAH Gene

Drugs & Compounds for PAH Gene

(40) Drugs for PAH Gene - From: DrugBank, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tetrahydrobiopterin Approved, Investigational Pharma cofactor, Target 0
Norepinephrine Approved Pharma Target, inhibitor 654
Droxidopa Approved, Investigational Pharma Target, inhibitor 27
Epinephrine Approved Pharma Target, antagonist 860
L-Phenylalanine Approved Nutra Target 0

(36) Additional Compounds for PAH Gene - From: Novoseek, IUPHAR, and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
4a-hydroxytetrahydrobiopterin
  • (6R)-6-(L-erythro-1,2-Dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin
  • 2-Amino-6-(1,2-dihydroxypropyl)-4a-hydroxy-5,6,7,8-tetrahydropteridin-4(4aH)-one
  • 2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxy-4(4aH)-Pteridinone
  • 2-Amino-6-[(1R,2S)-1,2-dihydroxypropyl]-4a-hydroxy-1,5,6,7-tetrahydropteridin-4-one
  • 4a-Hydroxy-5,6,7,8-tetrahydrobiopterin
70110-58-6
alpha-Methylphenylalanine
Inhibition, Inhibitor
Fe2+
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
15438-31-0
oxygen
  • Dioxygen
  • Molecular oxygen
  • O2
  • Oxygen
  • Oxygen molecule
7782-44-7
PCPA
Inhibition, Inhibitor

(1) ApexBio Compounds for PAH Gene

Compound Action Cas Number
WWL 70 α/β-hydrolase domain 6 inhibitor 947669-91-2
genes like me logo Genes that share compounds with PAH: view

Transcripts for PAH Gene

Unigene Clusters for PAH Gene

Phenylalanine hydroxylase:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for PAH Gene

No ASD Table

Relevant External Links for PAH Gene

GeneLoc Exon Structure for
PAH
ECgene alternative splicing isoforms for
PAH

Expression for PAH Gene

mRNA expression in normal human tissues for PAH Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PAH Gene

This gene is overexpressed in Liver (x43.4) and Kidney - Cortex (x6.3).

Protein differential expression in normal tissues from HIPED for PAH Gene

This gene is overexpressed in Gallbladder (21.2), Liver, secretome (18.5), Liver (16.9), and Fetal Liver (6.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for PAH Gene



SOURCE GeneReport for Unigene cluster for PAH Gene Hs.603740

genes like me logo Genes that share expression patterns with PAH: view

Protein tissue co-expression partners for PAH Gene

- Elite partner

No data available for mRNA Expression by UniProt/SwissProt for PAH Gene

Orthologs for PAH Gene

This gene was present in the common ancestor of animals.

Orthologs for PAH Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia PAH 35
  • 89.5 (n)
  • 92.68 (a)
PAH 36
  • 93 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PAH 35
  • 90.98 (n)
  • 95.12 (a)
PAH 36
  • 74 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Pah 35
  • 87.17 (n)
  • 92.48 (a)
Pah 16
Pah 36
  • 92 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia PAH 35
  • 99.71 (n)
  • 99.78 (a)
PAH 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Pah 35
  • 87.61 (n)
  • 92.26 (a)
oppossum
(Monodelphis domestica)
Mammalia PAH 36
  • 86 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PAH 36
  • 84 (a)
OneToOne
chicken
(Gallus gallus)
Aves PAH 35
  • 77.06 (n)
  • 83.26 (a)
PAH 36
  • 81 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PAH 36
  • 79 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia pah 35
  • 72.54 (n)
  • 77.96 (a)
zebrafish
(Danio rerio)
Actinopterygii pah 35
  • 69.99 (n)
  • 75.74 (a)
zgc65981 35
pah 36
  • 73 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.9738 35
fruit fly
(Drosophila melanogaster)
Insecta CG9122 37
  • 51 (a)
Hn 37
  • 62 (a)
ple 37
  • 49 (a)
Hn 35
  • 63.72 (n)
  • 63.72 (a)
Hn 36
  • 61 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005712 35
  • 60.71 (n)
  • 64.49 (a)
worm
(Caenorhabditis elegans)
Secernentea bas-2 37
  • 56 (a)
cat-2 37
  • 46 (a)
tph-1 37
  • 45 (a)
pah-1 35
  • 57.78 (n)
  • 58.73 (a)
pah-1 36
  • 55 (a)
OneToOne
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.1008 35
sea squirt
(Ciona savignyi)
Ascidiacea CSA.5653 36
  • 60 (a)
OneToOne
Species with no ortholog for PAH:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for PAH Gene

ENSEMBL:
Gene Tree for PAH (if available)
TreeFam:
Gene Tree for PAH (if available)

Paralogs for PAH Gene

Paralogs for PAH Gene

genes like me logo Genes that share paralogs with PAH: view

Variants for PAH Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for PAH Gene

PH4H_HUMAN-P00439
The Glu-274 variant occurs on approximately 4% of African-American PAH alleles. The enzyme activity of the variant protein is indistinguishable from that of the wild-type form.

Sequence variations from dbSNP and Humsavar for PAH Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
VAR_000869 Phenylketonuria (PKU)
VAR_000870 Hyperphenylalaninemia (HPA)
VAR_000870 Phenylketonuria (PKU)
VAR_000872 Phenylketonuria (PKU)
VAR_000873 Phenylketonuria (PKU)

Structural Variations from Database of Genomic Variants (DGV) for PAH Gene

Variant ID Type Subtype PubMed ID
nsv832500 CNV Loss 17160897
esv2746287 CNV Deletion 23290073
esv2370143 CNV Deletion 18987734
dgv215e201 CNV Deletion 23290073
esv1495220 CNV Deletion 17803354
esv2674462 CNV Deletion 23128226
esv2746289 CNV Deletion 23290073
esv2746290 CNV Deletion 23290073
esv2285780 CNV Deletion 18987734
esv2746291 CNV Deletion 23290073
esv2746292 CNV Deletion 23290073
esv1533666 CNV Deletion 17803354
esv274662 CNV Insertion 20981092

Variation tolerance for PAH Gene

Residual Variation Intolerance Score: 60.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.34; 41.65% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for PAH Gene

Human Gene Mutation Database (HGMD)
PAH

Disorders for PAH Gene

MalaCards: The human disease database

(18) MalaCards diseases for PAH Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search PAH in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

PH4H_HUMAN
  • Hyperphenylalaninemia (HPA) [MIM:261600]: Mildest form of phenylalanine hydroxylase deficiency. {ECO:0000269 PubMed:11385716, ECO:0000269 PubMed:11935335, ECO:0000269 PubMed:12501224, ECO:0000269 PubMed:1358789, ECO:0000269 PubMed:23792259, ECO:0000269 PubMed:8088845, ECO:0000269 PubMed:8098245, ECO:0000269 PubMed:9521426, ECO:0000269 PubMed:9852673}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Non-phenylketonuria hyperphenylalaninemia (Non-PKU HPA) [MIM:261600]: 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. {ECO:0000269 PubMed:1358789, ECO:0000269 PubMed:8088845, ECO:0000269 PubMed:8098245, ECO:0000269 PubMed:9521426, ECO:0000269 PubMed:9852673}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Phenylketonuria (PKU) [MIM:261600]: 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. {ECO:0000269 PubMed:10200057, ECO:0000269 PubMed:10679941, ECO:0000269 PubMed:11180595, ECO:0000269 PubMed:11385716, ECO:0000269 PubMed:11461196, ECO:0000269 PubMed:12501224, ECO:0000269 PubMed:1355066, ECO:0000269 PubMed:1363837, ECO:0000269 PubMed:1363838, ECO:0000269 PubMed:1671810, ECO:0000269 PubMed:1672290, ECO:0000269 PubMed:1672294, ECO:0000269 PubMed:1679030, ECO:0000269 PubMed:1709636, ECO:0000269 PubMed:1975559, ECO:0000269 PubMed:2014802, ECO:0000269 PubMed:22513348, ECO:0000269 PubMed:22526846, ECO:0000269 PubMed:23792259, ECO:0000269 PubMed:2564729, ECO:0000269 PubMed:2615649, ECO:0000269 PubMed:2840952, ECO:0000269 PubMed:7833954, ECO:0000269 PubMed:8068076, ECO:0000269 PubMed:8406445, ECO:0000269 PubMed:8889590, ECO:0000269 PubMed:9048935, ECO:0000269 PubMed:9101291, ECO:0000269 PubMed:9452061, ECO:0000269 PubMed:9452062, ECO:0000269 PubMed:9521426, ECO:0000269 PubMed:9600453, ECO:0000269 PubMed:9792407, ECO:0000269 PubMed:9950317}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for PAH Gene

phenylketonuria,hyperphenylalaninemia

Relevant External Links for PAH

Genetic Association Database (GAD)
PAH
Human Genome Epidemiology (HuGE) Navigator
PAH
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
PAH
genes like me logo Genes that share disorders with PAH: view

Publications for PAH Gene

  1. Substrate-induced conformational transition in human phenylalanine hydroxylase as studied by surface plasmon resonance analyses: the effect of terminal deletions, substrate analogues and phosphorylation. (PMID: 12379147) Stokka A.J. … Flatmark T. (Biochem. J. 2003) 3 23 25 26
  2. Molecular analysis of phenylketonuria (PKU) in newborns from Texas. (PMID: 11385716) Yang Y. … Garcia-Heras J. (Hum. Mutat. 2001) 3 4 48 67
  3. Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. (PMID: 9642259) Fusetti F. … Stevens R.C. (J. Biol. Chem. 1998) 3 23 25 26
  4. L-phenylalanine binding and domain organization in human phenylalanine hydroxylase: a differential scanning calorimetry study. (PMID: 12056888) ThA^rA^lfsson M. … MartA-nez A. (Biochemistry 2002) 3 25 26
  5. High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. (PMID: 11718561) Andersen O.A. … Hough E. (J. Mol. Biol. 2001) 3 23 26

Products for PAH Gene

Sources for PAH Gene

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