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Aliases for PAH Gene

Aliases for PAH Gene

  • Phenylalanine Hydroxylase 2 3
  • Phenylalanine 4-Monooxygenase 2 3
  • Phe-4-Monooxygenase 3 4
  • EC 4 63
  • PKU1 3 6
  • Phenylalanine-4-Hydroxylase 3
  • EC 1.14.16 63
  • 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 Disease and Metabolism. GO annotations related to this gene include iron ion binding and amino acid binding. 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

Genomic Location for PAH Gene

102,836,885 bp from pter
102,958,410 bp from pter
121,526 bases
Minus strand

Genomic View for PAH Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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:
    Recommended name:
    Protein Accession:
    Secondary Accessions:
    • Q16717
    • Q8TC14

    Protein attributes for PAH Gene

    452 amino acids
    Molecular mass:
    51862 Da
    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

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

Domains for PAH Gene

Gene Families for PAH Gene

Suggested Antigen Peptide Sequences for PAH Gene

Graphical View of Domain Structure for InterPro Entry



  • Contains 1 ACT domain.
  • Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
  • Contains 1 ACT domain.
  • 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 IDA 20667834
GO:0005506 iron ion binding IEA --
GO:0016597 amino acid binding IEA --
GO:0016714 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 --
genes like me logo Genes that share ontologies with PAH: view
genes like me logo Genes that share phenotypes with PAH: view

Animal Model Products

miRNA for PAH Gene

miRTarBase miRNAs that target PAH

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PAH

In Situ Assay Products

Flow Cytometry Products

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

Localization for PAH Gene

Subcellular locations from

Jensen Localization Image for PAH Gene COMPARTMENTS Subcellular localization image for PAH gene
Compartment Confidence
cytosol 4
extracellular 2
plasma membrane 2
mitochondrion 1
nucleus 1

Gene Ontology (GO) - Cellular Components for PAH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0070062 extracellular exosome IDA 23376485
genes like me logo Genes that share ontologies with PAH: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for PAH Gene

Pathways for PAH Gene

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

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

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:0006559 L-phenylalanine catabolic process TAS --
GO:0008152 metabolic process --
GO:0008652 cellular amino acid biosynthetic process TAS 3856322
GO:0009072 aromatic amino acid family metabolic process --
GO:0034641 cellular nitrogen compound metabolic process TAS --
genes like me logo Genes that share ontologies with PAH: view

Drugs for PAH Gene

(10) Drugbank Compounds for PAH Gene

Compound Status Synonyms Cas Number PubChem ID Type Actions PubMed IDs
  • Dops
23651-95-8 443940 Target inhibitor approved, investigational
  • (6R)-2-Amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydropteridin-4(1H)-one
17528-72-2 1125 Target cofactor approved, investigational
  • (S)-2-Amino-3-phenylpropionic acid
63-91-2 6140 Target approved, nutraceutical
  • (-)-(R)-Epinephrine
51-43-4 5816 Target antagonist approved
  • (-)-Arterenol
51-41-2 439260 Target inhibitor approved

(1) ApexBio Compounds for PAH Gene

Compound Action Cas Number
WWL 70 α/β-hydrolase domain 6 inhibitor [947669-91-2]

(13) HMDB Compounds for PAH Gene

Compound Synonyms Cas Number PubMed IDs
4a-Carbinolamine tetrahydrobiopterin
  • 1,3,5-Benzenetriol
  • (6R)-6-(L-erythro-1,2-Dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin
  • Droxydopa
  • (-)-(R)-Epinephrine
  • Armco iron

(2) IUPHAR Ligand for PAH Gene

Ligand Type Action Affinity Pubmed IDs
alpha-methylphenylalanine Inhibitor Inhibition
PCPA Inhibitor Inhibition

(61) Novoseek inferred chemical compound relationships for PAH Gene

Compound -log(P) Hits PubMed IDs
phenylalanine 97.3 283
hpah 94.4 18
tetrahydrobiopterin 94 111
4a-hydroxytetrahydrobiopterin 92.6 2
dihydropteridine 88.7 7
genes like me logo Genes that share compounds with PAH: view

Transcripts for PAH Gene

Unigene Clusters for PAH Gene

Phenylalanine hydroxylase:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PAH

Flow Cytometry Products

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

No ASD Table

Relevant External Links for PAH Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

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 (43.4) and Kidney - Cortex (6.3).

Protein differential expression in normal tissues 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 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 expressions with PAH: view

Expression partners for PAH Gene

* - Elite partner

Primer Products

In Situ Assay Products

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
(Bos Taurus)
Mammalia PAH 35
  • 89.5 (n)
  • 92.68 (a)
PAH 36
  • 93 (a)
(Canis familiaris)
Mammalia PAH 35
  • 90.98 (n)
  • 95.12 (a)
PAH 36
  • 74 (a)
(Mus musculus)
Mammalia Pah 35
  • 87.17 (n)
  • 92.48 (a)
Pah 16
Pah 36
  • 92 (a)
(Pan troglodytes)
Mammalia PAH 35
  • 99.71 (n)
  • 99.78 (a)
PAH 36
  • 100 (a)
(Rattus norvegicus)
Mammalia Pah 35
  • 87.61 (n)
  • 92.26 (a)
(Monodelphis domestica)
Mammalia PAH 36
  • 86 (a)
(Ornithorhynchus anatinus)
Mammalia PAH 36
  • 84 (a)
(Gallus gallus)
Aves PAH 35
  • 77.06 (n)
  • 83.26 (a)
PAH 36
  • 81 (a)
(Anolis carolinensis)
Reptilia PAH 36
  • 79 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia pah 35
  • 72.54 (n)
  • 77.96 (a)
(Danio rerio)
Actinopterygii pah 35
  • 69.99 (n)
  • 75.74 (a)
zgc65981 35
pah 36
  • 73 (a)
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)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005712 35
  • 60.71 (n)
  • 64.49 (a)
(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)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.1008 35
sea squirt
(Ciona savignyi)
Ascidiacea CSA.5653 36
  • 60 (a)
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

Gene Tree for PAH (if available)
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

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 MAF
rs772893 -- 102,845,831(-) GGTTG(A/G)GGAAC intron-variant
rs772894 -- 102,845,414(+) GCAGA(C/T)TGGGT intron-variant
rs772895 -- 102,845,283(+) ACAAT(A/T)TGTTC intron-variant
rs772896 -- 102,844,015(-) ACCAC(C/T)TTACT intron-variant
rs772897 untested 102,843,690(-) CCCCT(C/G)TATTA synonymous-codon, reference

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

Relevant External Links for PAH Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)
Locus Specific Mutation Databases (LSDB)

Disorders for PAH Gene

(1) OMIM Diseases for PAH Gene (612349)


  • 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.
  • 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. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • 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.

(2) University of Copenhagen DISEASES for PAH Gene

(20) Novoseek inferred disease relationships for PAH Gene

Disease -log(P) Hits PubMed IDs
phenylketonurias 98.4 117
hyperphenylalaninemia 98.2 115
phenylketonuria classical 94.3 23
phenylketonuria maternal 81 5
metabolic disorder 64.3 21

Genatlas disease for PAH Gene


Relevant External Links for PAH

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with PAH: view

Publications for PAH Gene

  1. Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. (PMID: 9642259) Fusetti F. … Stevens R.C. (J. Biol. Chem. 1998) 3 4 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 23 48
  3. 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 4 23 26
  4. 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
  5. Alterations in protein aggregation and degradation due to mild and severe missense mutations (A104D, R157N) in the human phenylalanine hydroxylase gene. (PMID: 9792411) Waters P.J. … Scriver C.R. (Hum. Mutat. 1998) 3 4 23

Products for PAH Gene

Sources for PAH Gene

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