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    PCBD1 pterin-4 alpha-carbinolamine dehydratase 1 [ Homo sapiens (human) ]

    Gene ID: 5092, updated on 27-Nov-2024

    Summary

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    Official Symbol
    PCBD1provided by HGNC
    Official Full Name
    pterin-4 alpha-carbinolamine dehydratase 1provided by HGNC
    Primary source
    HGNC:HGNC:8646
    See related
    Ensembl:ENSG00000166228 MIM:126090; AllianceGenome:HGNC:8646
    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
    PCD; PHS; DCOH; PCBD
    Summary
    This gene encodes a member of the pterin-4-alpha-carbinolamine dehydratase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. The encoded protein functions as both a dehydratase involved in tetrahydrobiopterin biosynthesis, and as a cofactor for HNF1A-dependent transcription. A deficiency of this enzyme leads to hyperphenylalaninemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
    Expression
    Ubiquitous expression in liver (RPKM 47.7), kidney (RPKM 31.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PCBD1 in Genome Data Viewer
    Location:
    10q22.1
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (70882280..70888565, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (71752084..71758371, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (72642037..72648322, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene ribosomal protein S26 pseudogene 40 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2451 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2452 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2453 Neighboring gene sphingosine-1-phosphate lyase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2454 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2455 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2457 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2456 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:72663371-72663919 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:72677493-72677667 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:72678259-72678439 Neighboring gene long intergenic non-protein coding RNA 2622 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:72730532-72731153 Neighboring gene uncharacterized LOC105378350 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:72740721-72741222 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:72741223-72741722 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2458

    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. Can the DCoHalpha isozyme compensate in patients with 4a-hydroxy-tetrahydrobiopterin dehydratase/DCoH deficiency? Hevel JM, et al. Mol Genet Metab, 2006 May. PMID 16423549
    2. Characterization of expression of the gene for human pterin carbinolamine dehydratase/dimerization cofactor of HNF1. Lei XD, et al. DNA Cell Biol, 1999 Mar. PMID 10098606
    3. Mutations in the pterin-4alpha-carbinolamine dehydratase (PCBD) gene cause a benign form of hyperphenylalaninemia. Thöny B, et al. Hum Genet, 1998 Aug. PMID 9760199
    4. Hyperphenylalaninemia with high levels of 7-biopterin is associated with mutations in the PCBD gene encoding the bifunctional protein pterin-4a-carbinolamine dehydratase and transcriptional coactivator (DCoH). Thöny B, et al. Am J Hum Genet, 1998 Jun. PMID 9585615, Free PMC Article
    5. Studies on the enzymatic and transcriptional activity of the dimerization cofactor for hepatocyte nuclear factor 1. Johnen G, et al. Proc Natl Acad Sci U S A, 1997 Dec 9. PMID 9391049, Free PMC Article

    See all (63) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. We provide the first genetic evidence that PCBD1 mutations can cause early-onset nonautoimmune diabetes with features similar to dominantly inherited HNF1A-diabetes.
      Title: Recessive mutations in PCBD1 cause a new type of early-onset diabetes.
    2. Coactivator of the HNFB1 (HNF1 homeobox B)-mediated transcription is necessary for fine tuning ATPase Na+/K+ transporting gamma 1 polypeptide (FXYD2) transcription in the distal convoluted tubule
      Title: Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting.
    3. Pcbd1 is a moonlighting protein that has dehydratase activity in addition to functioning as a cofactor which regulates HNF1alpha.
      Title: The bifunctional DCOH protein binds to HNF1 independently of its 4-alpha-carbinolamine dehydratase activity.
    4. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: Use of genome-wide expression data to mine the "Gray Zone" of GWA studies leads to novel candidate obesity genes.
    5. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
      Title: Examination of tetrahydrobiopterin pathway genes in autism.
    6. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.
    8. Data reveal DCoH/HNF-1 alpha expression and transcriptional activity in human epidermal melanocytes in vitro and in situ and identified tyrosinase, the key enzyme for pigmentation, as a new transcriptional target.
      Title: In situ and in vitro evidence for DCoH/HNF-1 alpha transcription of tyrosinase in human skin melanocytes.
    9. Properties of dehydratase/DCoHalpha are consistent with hypothesis that activity of this isozyme could account for relatively mild symptoms reported for patients with a defect in dehydratase/DCoH
      Title: Can the DCoHalpha isozyme compensate in patients with 4a-hydroxy-tetrahydrobiopterin dehydratase/DCoH deficiency?
    10. Albumin colocalized together with its transcription factor PCD/DCoH/HNF-1alpha in suprabasal keratinocytes in human full-thickness skin sections and in keratinocytes cultured in serum-free medium.
      Title: In vivo and in vitro evidence for autocrine DCoH/HNF-1alpha transcription of albumin in the human epidermis.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    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
    Pterin-4 alpha-carbinolamine dehydratase 1 deficiency
    MedGen: C1849700 OMIM: 264070 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    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 4-alpha-hydroxytetrahydrobiopterin dehydratase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables phenylalanine 4-monooxygenase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription coactivator activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in positive regulation of DNA-templated transcription IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tetrahydrobiopterin biosynthetic process IEA
    Inferred from Electronic Annotation
    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 IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    pterin-4-alpha-carbinolamine dehydratase
    Names
    4-alpha-hydroxy-tetrahydropterin dehydratase
    6-pyruvoyl-tetrahydropterin synthase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (TCF1)
    dimerizing cofactor for HNF1
    phenylalanine hydroxylase-stimulating protein
    pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha
    NP_000272.1
    NP_001276726.1
    NP_001309933.1

    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_008646.1 RefSeqGene

      Range
      5220..10275
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000281.4 → NP_000272.1  pterin-4-alpha-carbinolamine dehydratase isoform 1

      See identical proteins and their annotated locations for NP_000272.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes isoform 1.
      Source sequence(s)
      BC006324, BQ685076
      Consensus CDS
      CCDS31217.1
      UniProtKB/Swiss-Prot
      P61457, P70519, P80095, Q9D930
      UniProtKB/TrEMBL
      Q6FGB3
      Related
      ENSP00000299299.3, ENST00000299299.4
      Conserved Domains (1) summary
      cd00914
      Location:24 → 99
      PCD_DCoH_subfamily_b; PCD_DCoH: The bifunctional protein pterin-4alpha-carbinolamine dehydratase (PCD), also known as DCoH (dimerization cofactor of hepatocyte nuclear factor-1), is both a transcription activator and a metabolic enzyme. DCoH stimulates gene expression by ...

    2. NM_001289797.2 → NP_001276726.1  pterin-4-alpha-carbinolamine dehydratase isoform 3

      See identical proteins and their annotated locations for NP_001276726.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and uses a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      BC006324, BI548743
      UniProtKB/Swiss-Prot
      P61457
      Conserved Domains (1) summary
      cl00942
      Location:1 → 50
      PCD_DCoH; The bifunctional protein pterin-4alpha-carbinolamine dehydratase (PCD), also known as DCoH (dimerization cofactor of hepatocyte nuclear factor-1), is both a transcription activator and a metabolic enzyme. DCoH stimulates gene expression by associating ...

    3. NM_001323004.2 → NP_001309933.1  pterin-4-alpha-carbinolamine dehydratase isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (2) has an alternate C-terminus compared to isoform 1.
      Source sequence(s)
      AC073176, HY292808
      Related
      ENST00000493961.5
      Conserved Domains (1) summary
      cl00942
      Location:24 → 74
      PCD_DCoH; PCD_DCoH: The bifunctional protein pterin-4alpha-carbinolamine dehydratase (PCD), also known as DCoH (dimerization cofactor of hepatocyte nuclear factor-1), is both a transcription activator and a metabolic enzyme. DCoH stimulates gene expression by ...

    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_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      70882280..70888565 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      71752084..71758371 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001001939.1: Suppressed sequence

      Description
      NM_001001939.1: This RefSeq record was removed by NCBI staff. Contact [email protected] for further information.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P61457.2 GenPept UniProtKB/Swiss-Prot:P61457

    Gene LinkOut

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