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    PAH phenylalanine hydroxylase [ Homo sapiens (human) ]

    Gene ID: 5053, updated on 27-Dec-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (102836889..102958441, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (102797868..102919265, complement)
    RS_2024_09 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: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Identification and characterization of a novel liver-specific enhancer of the human phenylalanine hydroxylase gene. Chen KJ, et al. Hum Genet, 2002 Mar. PMID 11935335
    2. Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian patients with phenylketonuria. Acosta A, et al. Hum Mutat, 2001 Feb. PMID 11180595
    3. A silent mutation induces exon skipping in the phenylalanine hydroxylase gene in phenylketonuria. Chao HK, et al. Hum Genet, 2001 Jan. PMID 11214902
    4. Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine. Gjetting T, et al. Am J Hum Genet, 2001 Jun. PMID 11326337, Free PMC Article
    5. Molecular analysis of phenylketonuria (PKU) in newborns from Texas. Yang Y, et al. Hum Mutat, 2001 Jun. PMID 11385716

    See all (322) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. [Analysis of PAH gene variants and prenatal diagnosis for 43 Chinese pedigrees affected with Phenylketonuria].
      Title: [Analysis of PAH gene variants and prenatal diagnosis for 43 Chinese pedigrees affected with Phenylketonuria].
    2. Comprehensive analyses of phenylalanine hydroxylase variants and phenotypic characteristics of patients in the eastern region of Turkiye.
      Title: Comprehensive analyses of phenylalanine hydroxylase variants and phenotypic characteristics of patients in the eastern region of Türkiye.
    3. Genetic Landscape and Clinical Features of Hyperphenylalaninemia in North Ossetia-Alania: High Frequency of P281L and P211T Genetic Variants in the PAH Gene.
      Title: Genetic Landscape and Clinical Features of Hyperphenylalaninemia in North Ossetia-Alania: High Frequency of P281L and P211T Genetic Variants in the PAH Gene.
    4. [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].
    5. [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].
    6. 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.
    7. Deep Intronic PAH Variants Explain Missing Heritability in Hyperphenylalaninemia.
      Title: Deep Intronic PAH Variants Explain Missing Heritability in Hyperphenylalaninemia.
    8. 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.
    9. 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.
    10. Identification of Variants Underlying Phenylalanine Hydroxylase Deficiency in Saudi Arabia.
      Title: Identification of Variants Underlying Phenylalanine Hydroxylase Deficiency in Saudi Arabia.
    Submit: New GeneRIF Correction See all GeneRIFs (181)

    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
    		Compare labs

    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)

    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_2024_08

    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

      UniProtKB/TrEMBL
      B4DPN2
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P00439.1 GenPept UniProtKB/Swiss-Prot:P00439

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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