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PAH phenylalanine hydroxylase [ Homo sapiens (human) ]

Gene ID: 5053, updated on 21-Mar-2023

Summary

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Official Symbol
PAHprovided by HGNC
Official Full Name
phenylalanine hydroxylaseprovided by HGNC
Primary source
HGNC:HGNC:8582
See related
Ensembl:ENSG00000171759 MIM:612349; AllianceGenome:HGNC:8582
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
This gene encodes a member of the biopterin-dependent aromatic amino acid hydroxylase protein family. The encoded phenylalanine hydroxylase enzyme hydroxylates phenylalanine to tyrosine and is the rate-limiting step in phenylalanine catabolism. Deficiency of this enzyme activity results in the autosomal recessive disorder phenylketonuria. [provided by RefSeq, Aug 2017]
Expression
Biased expression in liver (RPKM 237.1), kidney (RPKM 166.4) and 1 other tissue See more
Orthologs
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Genomic context

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See PAH in Genome Data Viewer
Location:
12q23.2
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_03 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (102836889..102958441, complement)
RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (102797868..102919265, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (103230667..103352219, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 485 Neighboring gene Sharpr-MPRA regulatory region 11085 Neighboring gene uncharacterized LOC124902999 Neighboring gene uncharacterized LOC112267865 Neighboring gene VISTA enhancer hs1122 Neighboring gene VISTA enhancer hs1574 Neighboring gene achaete-scute family bHLH transcription factor 1 Neighboring gene VISTA enhancer hs1114

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Characterization of phenylalanine hydroxylase gene variants and analysis of genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Fujian Province, Southeastern China. Zhou J, et al. Mol Biol Rep, 2022 Nov. PMID 36104584, Free PMC Article
  2. An update of the mutation spectrum of phenylalanine hydroxylase (PAH) gene in the population of Turkey. Ozturk FN, et al. J Pediatr Endocrinol Metab, 2022 May 25. PMID 35405047
  3. Spectrum of PAH gene mutations and genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey. Çınar M, et al. J Pediatr Endocrinol Metab, 2022 May 25. PMID 35355500
  4. The pathogenicity classification of PAH gene variants in the Iranian population. Alibakhshi R, et al. Comput Biol Chem, 2022 Jun. PMID 35339094
  5. Frequency of PAH Mutations Among Classic Phenylketon Urea Patients in Mazandaran and Golestan Provinces, North of Iran. Hosseini E, et al. Clin Lab, 2022 Jan 1. PMID 35023679

See all (310) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Identifying and elucidating the roles of Y198N and Y204F mutations in the PAH enzyme through molecular dynamic simulations.
    Title: Identifying and elucidating the roles of Y198N and Y204F mutations in the PAH enzyme through molecular dynamic simulations.
  2. Characterization of phenylalanine hydroxylase gene variants and analysis of genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Fujian Province, Southeastern China.
    Title: Characterization of phenylalanine hydroxylase gene variants and analysis of genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Fujian Province, Southeastern China.
  3. Deubiquitinase USP19 extends the residual enzymatic activity of phenylalanine hydroxylase variants.
    Title: Deubiquitinase USP19 extends the residual enzymatic activity of phenylalanine hydroxylase variants.
  4. The pathogenicity classification of PAH gene variants in the Iranian population.
    Title: The pathogenicity classification of PAH gene variants in the Iranian population.
  5. An update of the mutation spectrum of phenylalanine hydroxylase (PAH) gene in the population of Turkey.
    Title: An update of the mutation spectrum of phenylalanine hydroxylase (PAH) gene in the population of Turkey.
  6. Spectrum of PAH gene mutations and genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey.
    Title: Spectrum of PAH gene mutations and genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey.
  7. An Updated PAH Mutational Spectrum of Phenylketonuria in Mexican Patients Attending a Single Center: Biochemical, Clinical-Genotyping Correlations.
    Title: An Updated PAH Mutational Spectrum of Phenylketonuria in Mexican Patients Attending a Single Center: Biochemical, Clinical-Genotyping Correlations.
  8. Spectrum of PAH gene mutations in 1547 phenylketonuria patients from Iran: a comprehensive systematic review.
    Title: Spectrum of PAH gene mutations in 1547 phenylketonuria patients from Iran: a comprehensive systematic review.
  9. Frequency of PAH Mutations Among Classic Phenylketon Urea Patients in Mazandaran and Golestan Provinces, North of Iran.
    Title: Frequency of PAH Mutations Among Classic Phenylketon Urea Patients in Mazandaran and Golestan Provinces, North of Iran.
  10. In silico screening and molecular dynamics simulation of deleterious PAH mutations responsible for phenylketonuria genetic disorder.
    Title: In silico screening and molecular dynamics simulation of deleterious PAH mutations responsible for phenylketonuria genetic disorder.
Submit: New GeneRIF Correction See all GeneRIFs (170)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Phenylketonuria
MedGen: C0031485 OMIM: 261600 GeneReviews: Phenylalanine Hydroxylase Deficiency
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EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites.
EBI GWAS Catalog

Variation

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See Variation Viewer (GRCh37.p13)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables iron ion binding IEA
Inferred from Electronic Annotation
more info
  
enables phenylalanine 4-monooxygenase activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables phenylalanine 4-monooxygenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in L-phenylalanine catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in amino acid biosynthetic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in catecholamine biosynthetic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in neurotransmitter biosynthetic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in tyrosine biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in tyrosine biosynthetic process, by oxidation of phenylalanine IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
phenylalanine-4-hydroxylase
Names
phe-4-monooxygenase
phenylalanine 4-monooxygenase
NP_000268.1
NP_001341233.1
XP_016874859.1
XP_054228125.1

NCBI Reference Sequences (RefSeq)

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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

  1. NG_008690.2 RefSeqGene

    Range
    46167..126522
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000277.3 → NP_000268.1  phenylalanine-4-hydroxylase

    See identical proteins and their annotated locations for NP_000268.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.
    Source sequence(s)
    AC069227, BC026251, BQ268294, U49897
    Consensus CDS
    CCDS9092.1
    UniProtKB/Swiss-Prot
    P00439, Q8TC14
    UniProtKB/TrEMBL
    A0A024RBG4
    Related
    ENSP00000448059.1, ENST00000553106.6
    Conserved Domains (1) summary
    TIGR01268
    Location:20 → 452
    Phe4hydrox_tetr; phenylalanine-4-hydroxylase, tetrameric form

  2. NM_001354304.2 → NP_001341233.1  phenylalanine-4-hydroxylase

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.
    Source sequence(s)
    AC026108, AC069227, BQ268294, DA299598
    Consensus CDS
    CCDS9092.1
    UniProtKB/Swiss-Prot
    Q8TC14
    UniProtKB/TrEMBL
    A0A024RBG4
    Conserved Domains (1) summary
    TIGR01268
    Location:20 → 452
    Phe4hydrox_tetr; phenylalanine-4-hydroxylase, tetrameric form

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    102836889..102958441 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017019370.2 → XP_016874859.1  phenylalanine-4-hydroxylase isoform X1

    Conserved Domains (1) summary
    TIGR01268
    Location:20 → 235
    Phe4hydrox_tetr; phenylalanine-4-hydroxylase, tetrameric form

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    102797868..102919265 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054372150.1 → XP_054228125.1  phenylalanine-4-hydroxylase isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P00439.1 GenPept UniProtKB/Swiss-Prot:P00439

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