Platelet-derived growth factor receptor alpha (PDGFRα) V651D mutant (PDGFRα V651D)

Platelet-derived growth factor receptor alpha (PDGFRα) is a cell-surface receptor tyrosine kinase that plays a critical role in regulating cell proliferation, survival, and development (UniProt P16234). The V651D mutation is a specific missense mutation located in exon 14, which encodes part of the ATP-binding domain of the kinase (Medina et al., 2005). This mutation leads to the constitutive, ligand-independent activation of the PDGFRα signaling pathway, driving oncogenesis in certain cancers, most notably gastrointestinal stromal tumors (GIST) (Heinrich et al., 2003). While less common than mutations in exon 18 (e.g., D842V) or exon 12 (e.g., V561D), the V651D variant is clinically significant as it influences the sensitivity of the tumor to tyrosine kinase inhibitors (TKIs) (Corless et al., 2005). Patients harboring this mutation are typically managed with TKIs such as imatinib or avapritinib, although the specific sensitivity profile can vary compared to the wild-type receptor (FDA Label: Ayvakit). Understanding the presence of the V651D mutation is essential for precision medicine approaches in GIST to optimize therapeutic selection and predict clinical outcomes (StatPearls: Gastrointestinal Stromal Tumors).

Other names

PDGFRA V651DCD140A V651DPlatelet-derived growth factor receptor 2 V651DPDGFR-alpha V651D

Tyrosine kinase inhibition via competitive binding to the ATP-binding pocket of the intracellular domain.