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

Summary

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

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_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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).
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

Associated conditions

Description	Tests
Familial X-linked hypophosphatemic vitamin D refractory rickets MedGen: C0733682 OMIM: 307800 GeneReviews: X-Linked Hypophosphatemia	not available

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 EBI GWAS CatalogPubMed
Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of proneness to anger. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of Tourette's syndrome. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

DXS7759 (e-PCR)
- UniSTS:81948

DXS1464 (e-PCR)
- UniSTS:148773

DXS1314 (e-PCR)
- UniSTS:99165

WI-13816 (e-PCR)
- UniSTS:15325

RH80232 (e-PCR)
- UniSTS:84720

DXS1464 (e-PCR)
- UniSTS:99569

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

NG_007563.3 RefSeqGene

Range

5002..223987

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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

NC_000023.11 Reference GRCh38.p14 Primary Assembly

Range

22032325..22251310

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Related

ENSP00000508264.1, ENST00000684143.1
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
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
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
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

NC_060947.1 Alternate T2T-CHM13v2.0

Range

21615666..21834723

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054327194.1 → XP_054183169.1 phosphate-regulating neutral endopeptidase PHEX isoform X3
XM_054327191.1 → XP_054183166.1 phosphate-regulating neutral endopeptidase PHEX isoform X1

UniProtKB/TrEMBL

B4DWG8
XM_054327193.1 → XP_054183168.1 phosphate-regulating neutral endopeptidase PHEX isoform X2
XM_054327192.1 → XP_054183167.1 phosphate-regulating neutral endopeptidase PHEX isoform X2
XM_054327195.1 → XP_054183170.1 phosphate-regulating neutral endopeptidase PHEX isoform X4