FGF23

Protein identityUniProt · HPA

UniProt accession

Q9GZV9

Gene

FGF23

Ensembl

ENSG00000118972

Chromosome

12

Canonical length

251 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted secreted proteins, RAS pathway related proteins, Transporters

Subcellular location

Nuclear bodies,Vesicles,Centrosome,Cytosol

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a member of the fibroblast growth factor family of proteins, which possess broad mitogenic and cell survival activities and are involved in a variety of biological processes. The product of this gene regulates phosphate homeostasis and transport in the kidney. The full-length, functional protein may be deactivated via cleavage into N-terminal and C-terminal chains. Mutation of this cleavage site causes autosomal dominant hypophosphatemic rickets (ADHR). Mutations in this gene are also associated with hyperphosphatemic familial tumoral calcinosis (HFTC). [provided by RefSeq, Feb 2013]

Canonical amino-acid sequenceUniProt

251 residues, UniProt reviewed canonical sequence.

>Q9GZV9|FGF23
     1  MLGARLRLWV CALCSVCSMS VLRAYPNASP LLGSSWGGLI HLYTATARNS YHLQIHKNGH
    61  VDGAPHQTIY SALMIRSEDA GFVVITGVMS RRYLCMDFRG NIFGSHYFDP ENCRFQHQTL
   121  ENGYDVYHSP QYHFLVSLGR AKRAFLPGMN PPPYSQFLSR RNEIPLIHFN TPIPRRHTRS
   181  AEDDSERDPL NVLKPRARMT PAPASCSQEL PSAEDNSPMA SDPLGVVRGG RVNTHAGGTG
   241  PEGCRPFAKF I

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FGF23 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

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

5.4 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FGF23.

Disease | AllUniProt

Conditions FGF23 is implicated in, by any mechanism.

• Hypophosphatemic rickets, autosomal dominant (ADHR) MIM:193100
• Tumoral calcinosis, hyperphosphatemic, familial, 2 (HFTC2) MIM:617993

Disease | GeneticClinVar

13 pathogenic / likely-pathogenic of 254 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal dominant hypophosphatemic rickets
• Tumoral calcinosis, hyperphosphatemic, familial, 2
• Tumoral calcinosis, hyperphosphatemic, familial, 1
• Hypophosphatemic rickets
• Short stature

ReferencesPubMed · IEDB

Publications for FGF23 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)

1.28

gnomAD pLI

0.03

gnomAD missense Z

0.4

DepMap mean gene effect

0.12

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 1% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• calcium ion homeostasis
• cellular response to interleukin-6
• cellular response to leptin stimulus
• cellular response to parathyroid hormone stimulus
• cellular response to vitamin D
• ERK1 and ERK2 cascade
• fibroblast growth factor receptor signaling pathway
• intracellular phosphate ion homeostasis
• negative regulation of bone mineralization
• negative regulation of hormone secretion
• negative regulation of osteoblast differentiation
• neurogenesis
• phosphate ion homeostasis
• positive regulation of cell population proliferation
• positive regulation of DNA-templated transcription
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of MAPK cascade
• positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway
• regulation of cell migration
• regulation of phosphate transport
• response to magnesium ion
• response to sodium phosphate
• vitamin D catabolic process
• positive regulation of vitamin D 24-hydroxylase activity

Molecular functions

• growth factor activity
• type 1 fibroblast growth factor receptor binding

Cellular components

• cytoplasm
• endoplasmic reticulum lumen
• extracellular region
• extracellular space
• Golgi lumen

Protein domainsUniProt · Pfam · InterPro

• Fibroblast growth factor family
• Cytokine IL1/FGF
• Fibroblast growth factor

KeywordsUniProt

• Differentiation
• Disulfide bond
• Glycoprotein
• Growth factor
• Phosphoprotein
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of FGF23 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FGFR1
• FGFR2
• FGFR3
• FGFR4
• KL