Редактирование: PHEX

Phosphate-regulating neutral endopeptidase PHEX (EC 3.4.24.-) (Metalloendopeptidase homolog PEX) (Vitamin D-resistant hypophosphatemic rickets protein) (X-linked hypophosphatemia protein) (HYP) [PEX]

==Publications==

{{medline-entry
|title=The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the "Fountain of Youth" to mediate healthful aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20227497
|abstract=The nuclear vitamin D receptor ([[VDR]]) binds 1,25-dihydroxyvitamin D3 (1,25D), its high affinity renal endocrine ligand, to signal intestinal calcium and phosphate absorption plus bone remodeling, generating a mineralized skeleton free of rickets/osteomalacia with a reduced risk of osteoporotic fractures. 1,25D/[[VDR]] signaling regulates the expression of [[TRPV6]], BGP, [[SPP1]], [[LRP5]], RANKL and OPG, while achieving feedback control of mineral ions to prevent age-related ectopic calcification by governing [[CYP24A1]], [[PTH]], [[FGF23]], [[PHEX]], and klotho transcription. Vitamin D also elicits numerous intracrine actions when circulating 25-hydroxyvitamin D3, the metabolite reflecting vitamin D status, is converted to 1,25D locally by extrarenal [[CYP27B1]], and binds [[VDR]] to promote immunoregulation, antimicrobial defense, xenobiotic detoxification, anti-inflammatory/anticancer actions and cardiovascular benefits. [[VDR]] also affects Wnt signaling through direct interaction with beta-catenin, ligand-dependently blunting beta-catenin mediated transcription in colon cancer cells to attenuate growth, while potentiating beta-catenin signaling via [[VDR]] ligand-independent mechanisms in osteoblasts and keratinocytes to function osteogenically and as a pro-hair cycling receptor, respectively. Finally, [[VDR]] also drives the mammalian hair cycle in conjunction with the hairless corepressor by repressing [[SOSTDC1]], S100A8/S100A9, and [[PTH]]rP. Hair provides a shield against UV-induced skin damage and cancer in terrestrial mammals, illuminating another function of [[VDR]] that facilitates healthful aging.
|mesh-terms=* Aging
* Animals
* Calcium
* Cell Nucleus
* Gene Expression Regulation
* Humans
* Keratinocytes
* Mice
* Models, Biological
* Osteopontin
* Phosphates
* Receptors, Calcitriol
* Signal Transduction
* Wnt Proteins
* beta Catenin

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906618
}}
{{medline-entry
|title=Vitamin D receptor genotype in hypophosphatemic rickets as a predictor of growth and response to treatment.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18827005
|abstract=Treatment of X-linked hypophosphatemic rickets improves bone mineralization and bone deformities, but its effect on skeletal growth is highly variable. Genetic variants in the promoter region of the vitamin D receptor ([[VDR]]) gene may explain the response to treatment because this receptor mediates vitamin D action. We studied the [[VDR]] promoter haplotype structure in a large cohort of 91 patients with hypophosphatemic rickets including 62 patients receiving 1alpha-hydroxyvitamin D3 derivatives and phosphates from early childhood on. Treatment improved bone deformities and final height, but 39% of treated patients still had short stature at the end of growth (-2 sd score or below). Height was closely associated with [[VDR]] promoter Hap1 genotype. Hap1(-) patients (35% of the cohort) had severe growth defects. This disadvantageous association of Hap1(-) status with height was visible before treatment, under treatment, and on to adulthood. Gender and age at initiation of treatment could not account for the Hap1 effect. No association with growth was found with a polymorphism of the [[PTH]] receptor gene otherwise found to be associated with adult height. Compared with Hap1( ) patients, those who were Hap1(-) had a higher urinary calcium response to 1alpha-hydroxyvitamin D3 and had significantly lower circulating [[FGF23]] levels (C-terminal assay), taking into account their phosphate and 1alpha-hydroxyvitamin D3 intakes. The present work identifies the [[VDR]] promoter genotype as a key predictor of growth under treatment with 1alpha-hydroxyvitamin D3 derivatives in patients with hypophosphatemic rickets, including those with established [[PHEX]] alterations. The [[VDR]] promoter genotype appears to provide valuable information for adjusting treatment and for deciding upon the utility of early GH therapy.
|mesh-terms=* Adolescent
* Adult
* Aging
* Calcitriol
* Child
* Child, Preschool
* Cohort Studies
* DNA
* Familial Hypophosphatemic Rickets
* Female
* Fibroblast Growth Factors
* Genetic Diseases, X-Linked
* Genotype
* Haplotypes
* Humans
* Male
* Middle Aged
* Organophosphates
* Predictive Value of Tests
* Promoter Regions, Genetic
* Receptor, Parathyroid Hormone, Type 1
* Receptors, Calcitriol
* Reverse Transcriptase Polymerase Chain Reaction
* Sex Characteristics
* Young Adult

|full-text-url=https://sci-hub.do/10.1210/jc.2007-2553
}}
{{medline-entry
|title=The regulation and function of phosphate in the human body.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15630224
|abstract=Inorganic phosphate (Pi) is required for cellular function and skeletal mineralization. Serum Pi level is maintained within a narrow range through a complex interplay between intestinal absorption, exchange with intracellular and bone storage pools, and renal tubular reabsorption. Pi is abundant in the diet, and intestinal absorption of Pi is efficient and minimally regulated. The kidney is a major regulator of Pi homeostasis and can increase or decrease its Pi reabsorptive capacity to accommodate Pi need. The crucial regulated step in Pi homeostasis is the transport of Pi across the renal proximal tubule. Type II sodium-dependent phosphate (Na/Pi) cotransporter (NPT2) is the major molecule in the renal proximal tubule and is regulated by hormones and nonhormonal factors. Recent studies of inherited and acquired hypophosphatemia which exhibit similar biochemical and clinical features, have led to the identification of novel genes, phosphate regulating gene with homologies to endopeptidases on the X chromosome ([[PHEX]]) and fibroblast growth factor-23 (FGF-23), that play a role in the regulation of Pi homeostasis. The [[PHEX]] gene encodes an endopeptidase, predominantly expressed in bone and teeth but not in kidney. FGF-23 may be a substrate of this endopeptidase and inhibit renal Pi reabsorption. In a survey in the United States and in Japan, the amount of phosphorus from food is gradually increasing. It is thought that excess amounts of phosphorus intake for long periods are a strong factor in bone impairment and ageing. The restriction of phosphorus intake seems to be important under low calcium intake to keep QOL on high level.
|mesh-terms=* Aging
* Chromosome Mapping
* Chromosomes, Human
* Chromosomes, Human, X
* Humans
* Hypophosphatemia, Familial
* Phosphates
* Quality of Life
* Sodium-Phosphate Cotransporter Proteins
* Sodium-Phosphate Cotransporter Proteins, Type I
* Sodium-Phosphate Cotransporter Proteins, Type II
* Sodium-Phosphate Cotransporter Proteins, Type III
* Symporters

|full-text-url=https://sci-hub.do/10.1002/biof.552210167
}}