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    PHEX phosphate regulating endopeptidase X-linked [ Homo sapiens (human) ]

    Gene ID: 5251, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PHEXprovided by HGNC
    Official Full Name
    phosphate regulating endopeptidase X-linkedprovided by HGNC
    Primary source
    HGNC:HGNC:8918
    See related
    Ensembl:ENSG00000102174 MIM:300550; AllianceGenome:HGNC:8918
    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
    HYP; PEX; XLH; HPDR; HYP1; LXHR; HPDR1
    Summary
    The protein encoded by this gene is a transmembrane endopeptidase that belongs to the type II integral membrane zinc-dependent endopeptidase family. The protein is thought to be involved in bone and dentin mineralization and renal phosphate reabsorption. Mutations in this gene cause X-linked hypophosphatemic rickets. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
    Expression
    Broad expression in lung (RPKM 1.3), endometrium (RPKM 1.1) and 15 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PHEX in Genome Data Viewer
    Location:
    Xp22.11
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (22032325..22251310)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (21615666..21834723)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (22050443..22269427)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20700 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20701 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29487 Neighboring gene CYTH1 pseudogene 1 Neighboring gene spermine synthase Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29488 Neighboring gene PHEX antisense RNA 1 Neighboring gene PTCHD1 antisense RNA (head to head) Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:22383141-22384340 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:22417737-22418936 Neighboring gene Cbl proto-oncogene like 2 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:22450970-22452169 Neighboring gene methyltransferase like 15 pseudogene 3

    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. Phosphate wasting in oncogenic osteomalacia: PHEX is normal and the tumor-derived factor has unique properties. Nelson AE, et al. Bone, 2001 Apr. PMID 11336925
    2. Effects of PHEX antisense in human osteoblast cells. Shih NR, et al. J Am Soc Nephrol, 2002 Feb. PMID 11805167
    3. Novel PHEX nonsense mutation in a patient with X-linked hypophosphatemic rickets and review of current therapeutic regimens. Kienitz T, et al. Exp Clin Endocrinol Diabetes, 2011 Jul. PMID 21553362
    4. Mutational analysis and genotype-phenotype correlation of the PHEX gene in X-linked hypophosphatemic rickets. Holm IA, et al. J Clin Endocrinol Metab, 2001 Aug. PMID 11502829
    5. X-linked hypophosphatemia attributable to pseudoexons of the PHEX gene. Christie PT, et al. J Clin Endocrinol Metab, 2001 Aug. PMID 11502821

    See all (133) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Characterization of Novel PHEX Variants in X-linked Hypophosphatemic Rickets and Genotype-PHEX Activity Correlation.
      Title: Characterization of Novel PHEX Variants in X-linked Hypophosphatemic Rickets and Genotype-PHEX Activity Correlation.
    2. A Mild Presentation of X-Linked Hypophosphatemia Caused by a Non-Canonical Splice Site Variant in the PHEX Gene.
      Title: A Mild Presentation of X-Linked Hypophosphatemia Caused by a Non-Canonical Splice Site Variant in the PHEX Gene.
    3. Impaired Growth Plate Maturation in XLH Is due to Both Excess FGF23 and Decreased 1,25-Dihydroxyvitamin D Signaling.
      Title: Impaired Growth Plate Maturation in XLH Is due to Both Excess FGF23 and Decreased 1,25-Dihydroxyvitamin D Signaling.
    4. Co-occurrence of Spondyloepiphyseal Dysplasia and X-Linked Hypophosphatemia in a Three-Generation Chinese Family.
      Title: Co-occurrence of Spondyloepiphyseal Dysplasia and X-Linked Hypophosphatemia in a Three-Generation Chinese Family.
    5. X-linked hypophosphatemia in 4 generations due to an exon 13-15 duplication in PHEX, in the absence of the c.*231A>G variant.
      Title: X-linked hypophosphatemia in 4 generations due to an exon 13-15 duplication in PHEX, in the absence of the c.*231A>G variant.
    6. Rare PHEX intron variant causes complete and severe phenotype in a family with hypophosphatemic rickets: a case report.
      Title: Rare PHEX intron variant causes complete and severe phenotype in a family with hypophosphatemic rickets: a case report.
    7. Whole exome sequencing identifies two novel variants in PHEX and DMP1 in Malaysian children with hypophosphatemic rickets.
      Title: Whole exome sequencing identifies two novel variants in PHEX and DMP1 in Malaysian children with hypophosphatemic rickets.
    8. A Unique Mechanism of a Novel Synonymous PHEX Variant Causing X-Linked Hypophosphatemia.
      Title: A Unique Mechanism of a Novel Synonymous PHEX Variant Causing X-Linked Hypophosphatemia.
    9. Novel PHEX gene locus-specific database: Comprehensive characterization of vast number of variants associated with X-linked hypophosphatemia (XLH).
      Title: Novel PHEX gene locus-specific database: Comprehensive characterization of vast number of variants associated with X-linked hypophosphatemia (XLH).
    10. Long-term effect of conventional phosphate and calcitriol treatment on metabolic recovery and catch-up growth in children with PHEX mutation.
      Title: Long-term effect of conventional phosphate and calcitriol treatment on metabolic recovery and catch-up growth in children with PHEX mutation.
    Submit: New GeneRIF Correction See all GeneRIFs (81)

    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

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2012-06-28)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2012-06-28)

    ClinGen Genome Curation Page

    EBI GWAS Catalog

    Description
    Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
    EBI GWAS Catalog
    Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients.
    EBI GWAS Catalog
    Genome-wide association study of proneness to anger.
    EBI GWAS Catalog
    Genome-wide association study of Tourette's syndrome.
    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 metalloendopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables zinc ion binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in bone development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in bone mineralization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell-cell signaling TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cellular response to parathyroid hormone stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to vitamin D IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in lung development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in odontogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in organophosphate metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein modification process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to growth hormone IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to insulin-like growth factor stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to sodium phosphate IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in skeletal system development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Golgi apparatus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    phosphate-regulating neutral endopeptidase PHEX
    Names
    PHEX peptidase
    X-linked hypophosphatemia protein
    metalloendopeptidase homolog PEX
    phosphate regulating endopeptidase homolog X-linked
    phosphate regulating gene with homologies to endopeptidases on the X chromosome (hypophosphatemia, vitamin D resistant rickets)
    vitamin D-resistant hypophosphatemic rickets protein

    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_007563.3 RefSeqGene

      Range
      5002..223987
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000444.6 → NP_000435.3  phosphate-regulating neutral endopeptidase PHEX isoform 1

      See identical proteins and their annotated locations for NP_000435.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AD000712, AK298030, U82970, Y10196
      Consensus CDS
      CCDS14204.1
      UniProtKB/Swiss-Prot
      O00678, P78562, Q13646, Q2M325, Q93032, Q99827
      UniProtKB/TrEMBL
      B4DNS0
      Related
      ENSP00000368682.4, ENST00000379374.5
      Conserved Domains (1) summary
      cd08662
      Location:74 → 747
      M13; Peptidase family M13 includes neprilysin, endothelin-converting enzyme I

    2. NM_001282754.2 → NP_001269683.1  phosphate-regulating neutral endopeptidase PHEX isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate exon in the 3' coding region, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (2) has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AD000712, AK298030, Y10196
      UniProtKB/TrEMBL
      B4DNS0
      Conserved Domains (1) summary
      cd08662
      Location:74 → 695
      M13; Peptidase family M13 includes neprilysin, endothelin-converting enzyme I

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      22032325..22251310
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047442159.1 → XP_047298115.1  phosphate-regulating neutral endopeptidase PHEX isoform X3

      UniProtKB/TrEMBL
      A0A804HLA0
      Related
      ENSP00000508264.1, ENST00000684143.1

    2. XM_024452390.2 → XP_024308158.1  phosphate-regulating neutral endopeptidase PHEX isoform X1

      UniProtKB/TrEMBL
      B4DNS0, B4DWG8
      Conserved Domains (1) summary
      cd08662
      Location:2 → 643
      M13; Peptidase family M13 includes neprilysin and endothelin-converting enzyme I

    3. XM_017029579.2 → XP_016885068.1  phosphate-regulating neutral endopeptidase PHEX isoform X2

      UniProtKB/TrEMBL
      B4E334
      Conserved Domains (1) summary
      cd08662
      Location:1 → 488
      M13; Peptidase family M13 includes neprilysin and endothelin-converting enzyme I

    4. XM_011545533.2 → XP_011543835.1  phosphate-regulating neutral endopeptidase PHEX isoform X2

      See identical proteins and their annotated locations for XP_011543835.1

      UniProtKB/TrEMBL
      B4E334
      Conserved Domains (1) summary
      cd08662
      Location:1 → 488
      M13; Peptidase family M13 includes neprilysin and endothelin-converting enzyme I

    5. XM_011545536.3 → XP_011543838.1  phosphate-regulating neutral endopeptidase PHEX isoform X4

      UniProtKB/TrEMBL
      B4E334
      Conserved Domains (1) summary
      cd08662
      Location:1 → 371
      M13; Peptidase family M13 includes neprilysin and endothelin-converting enzyme I

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      21615666..21834723
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054327194.1 → XP_054183169.1  phosphate-regulating neutral endopeptidase PHEX isoform X3

      UniProtKB/TrEMBL
      A0A804HLA0

    2. XM_054327191.1 → XP_054183166.1  phosphate-regulating neutral endopeptidase PHEX isoform X1

      UniProtKB/TrEMBL
      B4DNS0, B4DWG8

    3. XM_054327193.1 → XP_054183168.1  phosphate-regulating neutral endopeptidase PHEX isoform X2

      UniProtKB/TrEMBL
      B4E334

    4. XM_054327192.1 → XP_054183167.1  phosphate-regulating neutral endopeptidase PHEX isoform X2

      UniProtKB/TrEMBL
      B4E334

    5. XM_054327195.1 → XP_054183170.1  phosphate-regulating neutral endopeptidase PHEX isoform X4

      UniProtKB/TrEMBL
      B4E334
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P78562.1 GenPept UniProtKB/Swiss-Prot:P78562

    Gene LinkOut

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

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