PDGFRA Gene: Function, Mutations, and Associated Diseases

The PDGFRA gene encodes the platelet-derived growth factor receptor alpha, a cell surface receptor tyrosine kinase that binds platelet-derived growth factors (PDGFs). Upon ligand binding, it dimerizes and autophosphorylates, activating downstream signaling pathways such as RAS/MAPK, PI3K/AKT, and PLCγ, which regulate cell proliferation, survival, migration, and differentiation. PDGFRA is critical for embryonic development, particularly in the formation of the cranial mesenchyme, gonads, and gastrointestinal tract. Aberrant PDGFRA signaling, often due to mutations or overexpression, is implicated in various cancers, including gastrointestinal stromal tumors (GISTs), glioblastoma, and certain leukemias.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• RTK signaling

• RAS/MAPK cascade

• PI3K/AKT signaling

• PLCγ signaling

• PDGF signaling pathway

• Signaling by Receptor Tyrosine Kinases (Reactome)

PDGFRA is a single-pass type I transmembrane glycoprotein with an extracellular region containing five immunoglobulin-like domains, a transmembrane domain, and an intracellular tyrosine kinase domain split by a kinase insert. The receptor binds PDGF-A, -B, and -C chains with different affinities, forming homo- or heterodimers. Ligand binding induces receptor dimerization and autophosphorylation on specific tyrosine residues, creating docking sites for downstream signaling molecules. PDGFRA is essential for the development of various tissues, including the cranial mesenchyme, gonads, and gastrointestinal tract. In adults, it plays roles in wound healing and tissue repair. Aberrant activation of PDGFRA is a hallmark of several cancers, making it a therapeutic target for tyrosine kinase inhibitors like imatinib and avapritinib.