Calreticulin Mutant Protein (CALR mutant)

Calreticulin is a multifunctional, calcium-binding chaperone protein primarily located in the endoplasmic reticulum (ER). Mutations in the calreticulin gene (CALR) are most notably associated with certain myeloproliferative neoplasms (MPNs), where they drive disease pathogenesis through altered molecular interactions and signaling pathways. The most common mutations are insertions or deletions (INDELs) in exon 9 of CALR, resulting in a +1 frameshift that alters the C-terminal sequence and the loss of the KDEL ER-retention signal. Mutant calreticulin acquires a novel ability to bind directly to MPL (the thrombopoietin receptor), activating it independently of its ligand, which drives uncontrolled cell proliferation via JAK-STAT signaling.

Other names

Mutant CALRCALR exon 9 mutantCALR frameshift mutant

Targeting mutant CALR neoepitopes with cancer vaccines; Inhibition of the MPL-JAK2 pathway