U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Gene ID: 5251, updated on 3-Apr-2024

Summary

Go to the top of the page Help
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
See PHEX in Genome Data Viewer
Location:
Xp22.11
Exon count:
26
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (22032325..22251310)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (21615666..21834723)
105.20220307 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

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

Related articles in PubMed

  1. X-linked hypophosphatemia in 4 generations due to an exon 13-15 duplication in PHEX, in the absence of the c.*231A>G variant. Soto Barros J, et al. Bone, 2023 Jul. PMID 37059315,
  2. Rare PHEX intron variant causes complete and severe phenotype in a family with hypophosphatemic rickets: a case report. Aiello F, et al. J Pediatr Endocrinol Metab, 2023 Jan 27. PMID 36351286
  3. A Unique Mechanism of a Novel Synonymous PHEX Variant Causing X-Linked Hypophosphatemia. Alhamoudi KM, et al. J Clin Endocrinol Metab, 2022 Sep 28. PMID 35896147
  4. Novel PHEX gene locus-specific database: Comprehensive characterization of vast number of variants associated with X-linked hypophosphatemia (XLH). Sarafrazi S, et al. Hum Mutat, 2022 Feb. PMID 34806794, Free PMC Article
  5. Adult rheumatologic features, treatment and complications of X-linked hypophosphatemia. Salcion A, et al. Arch Pediatr, 2021 Oct. PMID 34625379

See all (128) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Spectrum of PHEX Mutations and FGF23 Profiles in a Taiwanese Cohort With X-Linked Hypophosphatemia Including 102 Patients.
    Title: Spectrum of PHEX Mutations and FGF23 Profiles in a Taiwanese Cohort With X-Linked Hypophosphatemia Including 102 Patients.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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).
  9. 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.
  10. Cellular and Molecular Alterations Underlying Abnormal Bone Growth in X-Linked Hypophosphatemia.
    Title: Cellular and Molecular Alterations Underlying Abnormal Bone Growth in X-Linked Hypophosphatemia.
Submit: New GeneRIF Correction See all GeneRIFs (80)

Phenotypes

Go to the top of the page Help

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

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

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

Go to the top of the page Help
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)

Go to the top of the page Help

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_2023_10

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

    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

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

    UniProtKB/TrEMBL
    B4DWG8

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

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

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

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.

Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools
Miscellaneous