CALR (Calreticulin) variants and mutations

CALR (also known as Calreticulin) is a human protein-coding gene encoding a calreticulin protein. It assists glycoprotein folding and buffers calcium within the endoplasmic reticulum. Somatic frameshift variants create abnormal C termini that activate thrombopoietin-receptor signaling and are major drivers of essential thrombocythemia and primary myelofibrosis. This analysis covers 620 CALR variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes neoplasm, myeloproliferative disorder, and thrombocythemia 1. Example CALR variants include L2V, L3R, and L3I.

Variant analysis overview

Gene: CALR
Protein: Calreticulin
UniProt accession: P27797
Organism: Homo sapiens
Variants analyzed: 620
Variant scope: all variants
Completed: 2026-08-18

Variant and mutation evidence

Variant composition: 443 unspecified-consequence records; 88 missense variants; 71 synonymous variants; 2 frameshift variants; 4 stop-gained variants; 2 splice-region variants; 3 in-frame deletions; 1 in-frame insertions; 6 substitution
Prediction scores: 485 variants have prediction scores (78% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: neoplasm, myeloproliferative disorder, thrombocythemia 1, primary myelofibrosis, hemorrhagic disease, neurodegenerative disease, essential thrombocythemia, Alzheimer disease, Parkinson disease, multiple sclerosis, lysosomal storage disease, myelofibrosis.

Protein structure and variant hotspots

Protein features: 9 binding sites; 5 post-translational modification sites.
PTM context: 7 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable CALR variants

Examples include L2V, L3R, L3I, L3L, S4P, S4S, V5G, V5M. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

CALR analysis run — CALR (620 variants) — completed 2026-08-18