Calreticulin(CALR) is an endoplasmic reticulum chaperone protein. Somatic insertions and deletions in exon 9 of calreticulin that cause a +1bp frameshift and a novel carboxy-terminal peptide in mutant calreticulin have been reported in 70% of JAK2/MPL-negative essential thrombocythemia (ET)and 56-88% of JAK2/MPL-negative primary myelofibrosis(PMF). In addition, CALR mutations have been reported in approximately 10% of patients with myelodysplasia, including JAK2/MPL-negative refractory anemia with ring sideroblasts (RARS-T) where it may co-occur with mutations in SF3B1. In ET, PMF, and RARS-T, calreticulin mutations appear to be mutually exclusive of mutations in JAK2 or MPL. The CALR mutations lead to loss of the endoplasmic reticulum retention motif (KDEL) sequence in the carboxy-terminal portion of mutant CALR. Calreticulin mutations appear to be absent in polycythemia vera, acute myeloid leukemia, chronic myeloid leukemia, systemic mastocytosis, lymphoid malignancies and are rare in atypical chronic myeloid leukemia and chronic myelomonocytic leukemia. The most common 52bp deletion mutation (Type 1) in CALR has been shown to lead to cytokine-independent growth and activation of STAT5. Type 2 (5 bp insertion) mutations have also been described. This represents a potentially targettable pathway alteration. Patients with some types of mutant CALR may show improved survival and lower risk of thrombosis compared to patients with mutant JAK2, according to some, but not all studies.

This gene is a known cancer gene.

This gene is a known cancer gene.