Calreticulin, mutant (CALR (mutant))

Mutant calreticulin refers to variants of the endoplasmic reticulum chaperone protein calreticulin that contain specific mutations (particularly in exon 9) associated with myeloproliferative neoplasms, notably essential thrombocythemia and primary myelofibrosis. These mutations alter the C-terminal domain, change the protein's ability to bind to the thrombopoietin receptor (MPL), and permit constitutive activation of downstream JAK-STAT signaling essential for the growth and survival of malignant hematopoietic clones. Mutant calreticulin proteins lose normal ER retention, disrupt proper glycoprotein folding, and drive oncogenesis via neomorphic gain-of-function mechanisms. CALR mutation testing is essential in the diagnosis and management of BCR-ABL–negative myeloproliferative neoplasms. If more granularity or protein isoform is needed, state the specific mutation (e.g., CALR Del52 or CALR Ins5) as a sub-type of mutant calreticulin.

Other names

calregulinCRP55CaBP3calsequestrin-like proteinendoplasmic reticulum resident protein 60 (ERp60)CALR mutantcrt mutantthrombocythemia-associated calreticulinprimary myelofibrosis-associated calreticulin

For druggable pathways: Inhibition of downstream JAK-STAT signaling via JAK inhibitors (indirect effect). Disruption of mutant calreticulin–thrombopoietin receptor (MPL) interaction (experimental approaches).