Fibroblast growth factor receptor 3c-alpha-Klotho complex (FGFR3c-KL) (FGFR3c-KL)

The Fibroblast growth factor receptor 3c-alpha-Klotho complex is a specialized heteromeric receptor system essential for endocrine fibroblast growth factor 23 (FGF23) signaling (Chen et al., Nature 2018). While FGFR1c is the primary mediator of FGF23 action in the kidney, FGFR3c also forms a high-affinity complex with the co-receptor alpha-Klotho to regulate mineral ion homeostasis (Kuro-o, M., Nature Reviews Nephrology 2019). This complex is primarily responsible for promoting urinary phosphate excretion and suppressing the synthesis of active vitamin D (1,25-dihydroxyvitamin D) (UniProt P22607). Dysregulation of this complex or its ligand is central to the pathogenesis of chronic kidney disease-mineral and bone disorder (CKD-MBD) and various forms of hypophosphatemic rickets (PubMed 29343892). Therapeutic strategies often focus on modulating this pathway, either by neutralizing excess FGF23 with monoclonal antibodies like Burosumab or by developing FGF23 mimetics to treat FGF23-deficient states (FDA Label: Crysvita). Understanding the structural assembly of the FGFR3c-Klotho complex is crucial for designing selective modulators that can correct phosphate imbalances without off-target effects on other FGFR isoforms.

Other names

FGFR3c-KlothoFGFR3-alpha-Klotho complexFGF23 receptor complexFGFR3c-KL complex

Modulation of the FGF23 signaling pathway through the FGFR-Klotho co-receptor complex to regulate renal phosphate handling and vitamin D synthesis.