ArticleThe Journal of clinical endocrinology and metabolism2009
Defective O-glycosylation due to a novel homozygous S129P mutation is associated with lack of fibroblast growth factor 23 secretion and tumoral calcinosis.
Article in The Journal of clinical endocrinology and metabolism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 67 citations in OpenAlex.
- The effects of elevated phosphate on the kidney - damaging the gatekeeper.Pflugers Archiv : European journal of physiology · 2026Review
- Clinical and Functional Characterization of Novel GALNT3 Mutations in a Chinese Child with Hyperphosphatemic Familial Tumoral Calcinosis.International journal of molecular sciences · 2026Article
- High Occurrence of a Missense Variant (c.471C>A) in theHuman mutation · 2025Article
- Fibroblast Growth Factor 23 Bone Regulation and Downstream Hormonal Activity.Calcified tissue international · 2023Review
- Phosphate Is a Cardiovascular Toxin.Advances in experimental medicine and biology · 2022Review
- A novelFrontiers in endocrinology · 2022Article
- Congenital Hyperphosphatemic Conditions Caused by the Deficient Activity of FGF23.Calcified tissue international · 2021Review
- Selective pharmacological inhibition of the sodium-dependent phosphate cotransporter NPT2a promotes phosphate excretion.The Journal of clinical investigation · 2020Article
- Hyperphosphatemic Tumoral Calcinosis: Pathogenesis, Clinical Presentation, and Challenges in Management.Frontiers in endocrinology · 2020Review
- FGF23 at the crossroads of phosphate, iron economy and erythropoiesis.Nature reviews. Nephrology · 2020Review
- FGF23 and Associated Disorders of Phosphate Wasting.Pediatric endocrinology reviews : PER · 2019Review
- The Role of Fibroblast Growth Factor 23 in Inflammation and Anemia.International journal of molecular sciences · 2019Review
- Sustained Klotho delivery reduces serum phosphate in a model of diabetic nephropathy.Journal of applied physiology (Bethesda, Md. : 1985) · 2019Article
- Increased FGF23 protects against detrimental cardio-renal consequences during elevated blood phosphate in CKD.JCI insight · 2019Article
- The EPO-FGF23 Signaling Pathway in Erythroid Progenitor Cells: Opening a New Area of Research.Frontiers in physiology · 2019Review
- FAM20C regulates osteoblast behaviors and intracellular signaling pathways in a cell-autonomous manner.Journal of cellular physiology · 2018Article
- FGF23 Actions on Target Tissues-With and Without Klotho.Frontiers in endocrinology · 2018Review
- Review
- Chronic Hyperphosphatemia and Vascular Calcification Are Reduced by Stable Delivery of Soluble Klotho.Journal of the American Society of Nephrology : JASN · 2017Article
- Inflammation regulates fibroblast growth factor 23 production.Current opinion in nephrology and hypertension · 2016Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHomozygous mutations in fibroblast growth factor (FGF23) have recently been described as the genetic cause of one form of hyperphosphatemic tumoral calcinosis (HFTC). However, it remained unclear to date how these mutations lead to loss of biologically active FGF23 in the circulation.
methodsWe here report a novel homozygous mutation, c.385T>C in FGF23 exon 2, which changes codon 129 from serine to proline (S129P) in a previously described individual affected by HFTC. The S129P mutation as well as two known FGF23 mutations, S71G and S129F, were introduced into an expression vector encoding wild-type (wt) human (h) FGF23 to yield [P129]hFGF23, [F129]hFGF23, and [G71]hFGF23; whole lysates, glycoprotein fractions, and conditioned media from HEK293 and COS-7 cells expressing these constructs were subjected to Western blot analysis using affinity-purified goat anti-hFGF23(51-69) and anti-hFGF23(206-222) antibodies.
resultsWe detected 25- and 32-kDa protein species in total lysates of HEK293 cells expressing wt-hFGF23. The 32-kDa band, representing O-glycosylated hFGF23, was not detectable in the glycoprotein fraction of lysates from HEK293 cells expressing [P129]hFGF23, and in comparison with wt-FGF23 only small amounts of [P129]hFGF23 were secreted into the medium. Similar results were obtained for cells expressing [G71]hFGF23 and [F129]hFGF23.
conclusionOur data for the first time directly show that FGF23 mutations associated with HFTC impair O-glycosylation in vitro resulting in poor secretion of the mutant hormone thereby explaining the characteristic hyperphosphatemic phenotype of homozygous carriers in vivo.
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