EPOR Gene: Erythropoietin Receptor – Function, Mutations, and Clinical Significance

The EPOR gene encodes the erythropoietin receptor, a transmembrane protein that binds erythropoietin (EPO) to regulate red blood cell production. Upon EPO binding, the receptor dimerizes and activates JAK2/STAT5 signaling, promoting erythroid progenitor survival, proliferation, and differentiation. Mutations in EPOR can lead to primary familial polycythemia (PFCP) or contribute to erythroleukemia.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Erythropoietin signaling pathway

• JAK-STAT signaling pathway

• Cytokine-cytokine receptor interaction

The erythropoietin receptor (EPOR) is a 508-amino acid transmembrane protein with an extracellular ligand-binding domain, a single transmembrane helix, and a cytoplasmic domain that lacks intrinsic kinase activity. Upon EPO binding, EPOR homodimerizes and activates JAK2, which phosphorylates STAT5, leading to transcription of genes essential for erythroid survival and differentiation. The receptor is primarily expressed on erythroid progenitor cells in the bone marrow. Mutations in the cytoplasmic domain often result in gain-of-function and familial polycythemia.