TFRC

TFRC encodes transferrin receptor protein 1 (TfR1/CD71), the major cell-surface receptor for cellular iron import. It is a homodimeric type II transmembrane glycoprotein that preferentially binds diferric (holo-)transferrin and internalizes the ligand-receptor complex via clathrin/AP-2-mediated endocytosis; iron is released in acidic endosomes (pH <= 5.5) and the apo-transferrin/TfR1 complex is recycled to the plasma membrane, completing the cycle in approximately 10-20 minutes. Internalization depends on the cytoplasmic tyrosine-based YTRF motif, and germline variants affecting this region cause an internalization defect and combined immunodeficiency, identifying TfR1 as a non-redundant immune-metabolic checkpoint that supplies iron for lymphocyte proliferation and mitochondrial metabolism. A proteolytically shed soluble ectodomain (sTfR) circulates and serves as a clinical biomarker of iron demand/erythropoiesis. TfR1 is also exploited pathologically as an entry receptor by several viruses/pathogens and is a leading target for receptor-mediated transcytosis across the blood-brain barrier and for CD71-based cancer-targeted delivery.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

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