Driver mutations in these genes (JAK2 p.V617F or exon 12 mutations, CALR exon 9 insertions and deletions, and MPL W515 mutations) lead to the constitutive activation of associated receptors and the subsequent amplification of downstream signalling pathways, which result in the aberrant cell proliferation in MPN. The gene discussed is CALR; the disease is myeloproliferative neoplasm.