FGF23 signalling in Hypophosphatemic rickets (Homo sapiens)

From WikiPathways

Jump to: navigation, search
1Gastro-intestinal tractSystemic circulationOsteoblastThyroid glandOsteoblastFGF23 degradationRicketsCalcitrolPhosphate lossProprotein convertasesOsteomalaciaPhosphateabsorptionChondrocyte differentiationpASARMFGF23 signallingStabilisation ofnuclear alphaHIF-1Activated renin angiotensin systemHydroxyapatiteformationHydroxyapatiteActin skeleton reorganisationMalaciaIron deficiencyHypophosphataemiaKLOTHO deficiencyPhosphate liberatedfrom pyrophosphateCalcitrolRicketsORAI1ROS1NFKB2NFKB1FGFR3CYP11B2PHEXPyrophosphateFGF23calciumDMP1FAM20CPTHDMP1ALPLENPP1CDKN1AKL25-Hydroxyvitamin DPhosphorousSPP1CYP27B1GALNT3SLC34A1CCND1PHEXCYP27B1CYP24A1Locally producedcalcitrolFGFR2CYP27B1CYP24A1KidneySLC34A3OMIM:617993Tumoral Calcinosis, Hyperphosphatemic, Familial, 2OMIM:241520Hypophosphatemic Rickets, Autosomal Recessive, 1OMIM:193100Hypophosphatemic Rickets, Autosomal DominantOMIM:613312Hypophosphatemic Rickets, Autosomal Recessive, 2OMIM:241520Hypophosphatemic Rickets, Autosomal Recessive, 1OMIM:264700Vitamin D Hydroxylation-Deficient Rickets, Type 1AOMIM:146000HypochondroplasiaOMIM:610474Camptodactyly, Tall Stature, And Hearing Loss SyndromeOMIM:187601Thanatophoric Dysplasia, Type IIOMIM:264700Vitamin D Hydroxylation-Deficient Rickets, Type 1AOMIM:241530Hypophosphatemic Rickets With Hypercalciuria, HereditaryOMIM:616482Achondroplasia, Severe, With Developmental Delay And Acanthosis NigricansOMIM:307800Hypophosphatemic Rickets, X-Linked DominantOMIM:307800Hypophosphatemic Rickets, X-Linked DominantOMIM:602849Muenke SyndromeOMIM:264700Vitamin D Hydroxylation-Deficient Rickets, Type 1AOMIM:123790Beare-Stevenson Cutis Gyrata SyndromeOMIM:101200Apert SyndromeOMIM:211900Tumoral Calcinosis, Hyperphosphatemic, Familial, 1OMIM:259775Raine SyndromeOMIM:100800AchondroplasiaOMIM:187600Thanatophoric Dysplasia, Type IOMIM:612247Crouzon Syndrome With Acanthosis NigricansOMIM:146300Hypophosphatasia, AdultOMIM:149730Lacrimoauriculodentodigital SyndromeOMIM:101600Pfeiffer SyndromeOMIM:617994Tumoral Calcinosis, Hyperphosphatemic, Familial, 3OMIM:614592Bent Bone Dysplasia SyndromeOMIM:123500Crouzon SyndromeOMIM:241500Hypophosphatasia, Infantile


Description

Taken from FGF23 and its role in X-linked hypophosphatemia-related morbidity by Signe Sparre Beck-Nielsen, Zulf Mughal, Dieter Haffner, Ola Nilsson, Elena Levtchenko, Gema Ariceta, Carmen de Lucas Collantes, Dirk Schnabel, Ravi Jandhyala and Outi Mäkitie [1].

X-linked hypophosphatemia (XLH) is an inherited disease of phosphate metabolism in which inactivating mutations of the Phosphate Regulating Endopeptidase Homolog, X-Linked (PHEX) gene lead to local and systemic effects including impaired growth, rickets, osteomalacia, bone abnormalities, bone pain, spontaneous dental abscesses, hearing difficulties, enthesopathy, osteoarthritis, and muscular dysfunction. Patients with XLH present with elevated levels of fibroblast growth factor 23 (FGF23), which is thought to mediate many of the aforementioned manifestations of the disease. Elevated FGF23 has also been observed in many other diseases of hypophosphatemia, and a range of animal models have been developed to study these diseases, yet the role of FGF23 in the pathophysiology of XLH is incompletely understood.

Regulation of FGF23 expression and secretion in XLH. Inactivating mutations in PHEX increase fibroblast growth factor 23 (FGF23) expression by increasing levels of acidic serine aspartate-rich-MEPE-associated protein (ASARM) peptide. This leads to increased release of FGF23 into the serum, and increased levels of FGF23-mediated signalling.

The pathway illustrates hypophosphatemic and autocrine/paracrine molecular pathways that have been proposed to link FGF23 to bone abnormalities in XLH.

Linked with a dotted arrow to the GeneProduct nodes are diseases caused by mutation in the respective gene.

Quality Tags

Ontology Terms

 

Bibliography

  1. Beck-Nielsen SS, Mughal Z, Haffner D, Nilsson O, Levtchenko E, Ariceta G, de Lucas Collantes C, Schnabel D, Jandhyala R, Mäkitie O; ''FGF23 and its role in X-linked hypophosphatemia-related morbidity.''; Orphanet J Rare Dis, 2019 PubMed Europe PMC Scholia

History

CompareRevisionActionTimeUserComment
110637view08:41, 23 May 2020Azanklfixed unconnected lines
108845view23:21, 2 February 2020RleeFixed 1 unconnected line.
108838view02:00, 1 February 2020RleeModified description
108837view02:00, 1 February 2020RleeNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
25-Hydroxyvitamin DMetaboliteCHEBI:86319 (ChEBI)
ALPLGeneProductENSG00000162551 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CDKN1AGeneProductENSG00000124762 (Ensembl)
CYP11B2GeneProductENSG00000179142 (Ensembl)
CYP24A1GeneProductENSG00000019186 (Ensembl)
CYP27B1GeneProductENSG00000111012 (Ensembl)
DMP1GeneProductENSG00000152592 (Ensembl)
ENPP1GeneProductENSG00000197594 (Ensembl)
FAM20CGeneProductENSG00000177706 (Ensembl)
FGF23GeneProductENSG00000118972 (Ensembl)
FGFR2GeneProductENSG00000066468 (Ensembl)
FGFR3GeneProductENSG00000068078 (Ensembl)
GALNT3GeneProductENSG00000115339 (Ensembl)
KLGeneProductENSG00000133116 (Ensembl)
NFKB1GeneProductENSG00000109320 (Ensembl)
NFKB2GeneProductENSG00000077150 (Ensembl)
ORAI1GeneProductENSG00000276045 (Ensembl)
PHEXGeneProductENSG00000102174 (Ensembl)
PTHGeneProductENSG00000152266 (Ensembl)
PhosphorousMetaboliteCHEBI:30207 (ChEBI)
PyrophosphateMetaboliteCHEBI:29888 (ChEBI)
ROS1GeneProductENSG00000047936 (Ensembl)
SLC34A1GeneProductENSG00000131183 (Ensembl)
SLC34A3GeneProductENSG00000198569 (Ensembl)
SPP1GeneProductENSG00000118785 (Ensembl)
calciumMetaboliteCHEBI:22984 (ChEBI)

Annotated Interactions

No annotated interactions

Personal tools