Mutant calreticulin C-terminus (CALR mutant C-terminus (or CALR^MUT^ C-terminus))

The mutant CALR C-terminus is a pathogenic neo-morphic protein segment resulting from frameshift mutations in the calreticulin gene (CALR), most frequently observed in patients with myeloproliferative neoplasms[4][5]. Unlike the wild-type, which ends in a negatively charged ER-retention motif (KDEL), these mutants replace the C-terminal with a highly positively charged sequence rich in lysine and arginine, losing the KDEL signal[3]. This mutant tail confers new functions: it binds specifically and stably to the Thrombopoietin receptor (MPL/TpoR), induces dimerization and activation of MPL, and drives cytokine-independent cell proliferation, transforming cells into a leukemic phenotype[4][5][1][2]. The mutant CALR C-terminus thus becomes both a driver of disease and a promising immunological target, as its neo-epitope is absent in normal tissues, allowing for potential selective therapy[6]. The oncogenic function is independent of exact residue composition but requires the overall positive charge and structural disorder of the mutant region[1][3].

Other names

Mutant CALR C-domainCALR^MUT^ C-terminusCALR Del52 C-terminusCALR Ins5 C-terminusMPN-associated CALR mutant C-terminus

Constitutive activation of the Thrombopoietin receptor (MPL/TpoR) via stable interaction of mutant CALR C-terminus, inducing cytokine-independent signal transduction and cell proliferation