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

Gene ID: 5251, updated on 3-Mar-2026
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
all
Try the new Gene page
Try the new Transcripts and proteins table
See PHEX in Genome Data Viewer
Location:
Xp22.11
Exon count:
26
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (22032325..22251310)
RS_2025_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 and PHEX antisense RNA 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

Go to nucleotide: Graphics FASTA GenBank

  • 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

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)

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

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables hydrolase activity IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables metalloendopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables metalloendopeptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables metalloendopeptidase activity TAS
Traceable Author Statement
more info
 PubMed 
enables metallopeptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables peptidase activity IEA
Inferred from Electronic Annotation
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 biomineral tissue development IEA
Inferred from Electronic Annotation
more info
  
involved_in bone development 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 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 proteolysis IEA
Inferred from Electronic Annotation
more info
  
involved_in proteolysis TAS
Traceable Author Statement
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 response to vitamin D 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
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
 PubMed 
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

NEW Try the new Transcript table

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_2025_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

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