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PAH phenylalanine hydroxylase [ Homo sapiens (human) ]

Gene ID: 5053, updated on 3-Apr-2024

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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Location:
12q23.2
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (102836889..102958441, complement)
RS_2023_10 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 2456 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23056 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr12:102814900-102816099 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23075/23079 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:102869029-102869530 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:102869531-102870030 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6881 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6882 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6883 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6884 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6885 Neighboring gene insulin like growth factor 1 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr12:102933234-102934433 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr12:103115830-103116467 Neighboring gene Sharpr-MPRA regulatory region 11085 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:103218752-103218929 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:103226259-103226804 Neighboring gene NANOG hESC enhancer GRCh37_chr12:103232984-103233485 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:103244689-103245888 Neighboring gene long intergenic non-protein coding RNA 485 Neighboring gene uncharacterized LOC124902999 Neighboring gene uncharacterized LOC112267865 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:103343731-103344658 Neighboring gene VISTA enhancer hs1122 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:103351919-103352450 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:103352451-103352982 Neighboring gene VISTA enhancer hs1574 Neighboring gene VISTA enhancer hs1114 Neighboring gene VISTA enhancers hs998, hs1354 and hs1540 Neighboring gene achaete-scute family bHLH transcription factor 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4776 Neighboring gene VISTA enhancer hs967 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6886 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6887 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4777 Neighboring gene U7 small nuclear RNA Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6888 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6889 Neighboring gene chromosome 12 open reading frame 42 Neighboring gene C12orf42 antisense RNA 1

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. Identification of Variants Underlying Phenylalanine Hydroxylase Deficiency in Saudi Arabia. Balobaid A, et al. Genet Test Mol Biomarkers, 2023 May. PMID 37257178
  2. The spectrum of phenylalanine hydroxylase variants and genotype-phenotype correlation in phenylketonuria patients in Gansu, China. Zhang C, et al. Hum Genomics, 2023 Apr 25. PMID 37098607, Free PMC Article
  3. 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
  4. 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
  5. 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

See all (313) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. [In vitro expression and functional analyses of the mutants p.R243Q, p.R241C and p.Y356X of the human phenylalanine hydroxylase].
    Title: [In vitro expression and functional analyses of the mutants p.R243Q, p.R241C and p.Y356X of the human phenylalanine hydroxylase].
  2. [Analysis of pathogenicity and genotype-phenotype correlation of the c.158G>A variant of phenylalanine hydroxylase gene].
    Title: [Analysis of pathogenicity and genotype-phenotype correlation of the c.158G>A variant of phenylalanine hydroxylase gene].
  3. Newborn screening and genetic features of patients with hyperphenylalaninemia in a southern Chinese population.
    Title: Newborn screening and genetic features of patients with hyperphenylalaninemia in a southern Chinese population.
  4. Deep Intronic PAH Variants Explain Missing Heritability in Hyperphenylalaninemia.
    Title: Deep Intronic PAH Variants Explain Missing Heritability in Hyperphenylalaninemia.
  5. Identification of deep intronic variants of PAH in phenylketonuria using full-length gene sequencing.
    Title: Identification of deep intronic variants of PAH in phenylketonuria using full-length gene sequencing.
  6. Mutation Characteristics of Phenylalanine Hydroxylase Gene in Children with Phenylketonuria in Yinchuan City.
    Title: Mutation Characteristics of Phenylalanine Hydroxylase Gene in Children with Phenylketonuria in Yinchuan City.
  7. Identification of Variants Underlying Phenylalanine Hydroxylase Deficiency in Saudi Arabia.
    Title: Identification of Variants Underlying Phenylalanine Hydroxylase Deficiency in Saudi Arabia.
  8. The spectrum of phenylalanine hydroxylase variants and genotype-phenotype correlation in phenylketonuria patients in Gansu, China.
    Title: The spectrum of phenylalanine hydroxylase variants and genotype-phenotype correlation in phenylketonuria patients in Gansu, China.
  9. 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.
  10. 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.
Submit: New GeneRIF Correction See all GeneRIFs (178)

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 variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

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
  
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 tyrosine biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
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, Q16717, Q8TC14
    UniProtKB/TrEMBL
    B2R8I4, Q8TEY0
    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
    P00439, Q16717, Q8TC14
    UniProtKB/TrEMBL
    B2R8I4, Q8TEY0
    Conserved Domains (1) summary
    TIGR01268
    Location:20 → 452
    Phe4hydrox_tetr; phenylalanine-4-hydroxylase, tetrameric form

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    UniProtKB/TrEMBL
    B4DPN2
    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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