PHEX

Protein identityUniProt · HPA

UniProt accession

P78562

Gene

PHEX

Ensembl

ENSG00000102174

Chromosome

X

Canonical length

749 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Vesicles,Plasma membrane

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

749 residues, UniProt reviewed canonical sequence.

>P78562|PHEX
     1  MEAETGSSVE TGKKANRGTR IALVVFVGGT LVLGTILFLV SQGLLSLQAK QEYCLKPECI
    61  EAAAAILSKV NLSVDPCDNF FRFACDGWIS NNPIPEDMPS YGVYPWLRHN VDLKLKELLE
   121  KSISRRRDTE AIQKAKILYS SCMNEKAIEK ADAKPLLHIL RHSPFRWPVL ESNIGPEGVW
   181  SERKFSLLQT LATFRGQYSN SVFIRLYVSP DDKASNEHIL KLDQATLSLA VREDYLDNST
   241  EAKSYRDALY KFMVDTAVLL GANSSRAEHD MKSVLRLEIK IAEIMIPHEN RTSEAMYNKM
   301  NISELSAMIP QFDWLGYIKK VIDTRLYPHL KDISPSENVV VRVPQYFKDL FRILGSERKK
   361  TIANYLVWRM VYSRIPNLSR RFQYRWLEFS RVIQGTTTLL PQWDKCVNFI ESALPYVVGK
   421  MFVDVYFQED KKEMMEELVE GVRWAFIDML EKENEWMDAG TKRKAKEKAR AVLAKVGYPE
   481  FIMNDTHVNE DLKAIKFSEA DYFGNVLQTR KYLAQSDFFW LRKAVPKTEW FTNPTTVNAF
   541  YSASTNQIRF PAGELQKPFF WGTEYPRSLS YGAIGVIVGH EFTHGFDNNG RKYDKNGNLD
   601  PWWSTESEEK FKEKTKCMIN QYSNYYWKKA GLNVKGKRTL GENIADNGGL REAFRAYRKW
   661  INDRRQGLEE PLLPGITFTN NQLFFLSYAH VRCNSYRPEA AREQVQIGAH SPPQFRVNGA
   721  ISNFEEFQKA FNCPPNSTMN RGMDSCRLW

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PHEX can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

4.8 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PHEX.

Disease | AllUniProt

Conditions PHEX is implicated in, by any mechanism.

• Hypophosphatemic rickets, X-linked dominant (XLHRD) MIM:307800

Disease | GeneticClinVar

865 pathogenic / likely-pathogenic of 1,548 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial X-linked hypophosphatemic vitamin D refractory rickets
• Hypophosphatemic rickets
• Thyroid cancer, nonmedullary, 1
• Hypophosphataemia or rickets
• PHEX-related disorder

ReferencesPubMed · IEDB

Publications for PHEX from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.14

gnomAD pLI

1

gnomAD missense Z

1.71

DepMap mean gene effect

0.14

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• bone development
• bone mineralization
• cell-cell signaling
• cellular response to parathyroid hormone stimulus
• cellular response to vitamin D
• lung development
• odontogenesis
• protein modification process
• protein processing
• proteolysis
• response to growth hormone
• response to insulin-like growth factor stimulus
• response to sodium phosphate
• skeletal system development
• organophosphate metabolic process

Molecular functions

• metalloendopeptidase activity
• zinc ion binding

Cellular components

• endoplasmic reticulum
• Golgi apparatus
• perinuclear region of cytoplasm
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Peptidase M13
• Peptidase M13, N-terminal domain
• Peptidase M13, C-terminal domain
• Metallopeptidase, catalytic domain superfamily
• Peptidase M13, domain 2
• Peptidase family M13
• Peptidase family M13

KeywordsUniProt

• Biomineralization
• Cell membrane
• Disulfide bond
• Glycoprotein
• Hydrolase
• Membrane
• Metal-binding
• Metalloprotease
• Protease
• Signal-anchor
• Transmembrane
• Transmembrane helix
• Zinc

InteractionsUniProt · HPA

Protein binding partners of PHEX in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MEPE