CALCA gene

The CALCA gene (CALCA stands for: Calcitonin Related Polypeptide Alpha) is a protein-coding gene located on chromosome 11p15.2. The CALCA gene encodes the peptide hormones calcitonin, the calcitonin gene-related peptide and the peptide catacalcin.

These peptide hormones are produced by tissue-specific alternative RNA splicing of the gene transcripts and by cleavage of inactive precursor proteins. Several transcript variants encoding different isoforms have been found for the CALCA gene. An important paralog of this gene is CALCB.

Diseases associated with CALCA include:

• complex regional pain syndrome and
• reflex sympathetic dystrophy.

In restless legs syndrome (RLS ), a common sensory-motor disorder, recent therapeutic approaches are based on the assumption of dysfunction of nucleus A11, which modulates dopaminergic transmission to the spinal cord. The calcitonin gene-related peptide (CGRP), which is involved in pain modulation, appears to interact with the A11 signaling pathways, suggesting a role in RLS (Mogavero MP et al. 2025; Suzuki K et al.2025).

1. Cao J et al. (2022) A structural basis for amylin receptor phenotype. Science 375:eabm9609.
2. Kitamura K et al. (1992) Isolation and characterization of peptides which act on rat platelets, from a pheochromocytoma. Biochem Biophys Res Commun 185:134-141
3. Josephs TM et al. (2021) Structure and dynamics of the CGRP receptor in apo and peptide-bound forms. Science 372:eabf7258.
4. McLatchie LM et al. (1998) RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393:333-339.
5. Mogavero MP et al. (2025) Involvement of the Calcitonin Gene-Related Peptide in Restless Legs Syndrome. Mov Disord 40:1148-1159.
6. Suzuki K et al.(2025) The effect of calcitonin gene-related peptide monoclonal antibodies on restless legs syndrome in patients with migraine. J Headache Pain 26:36.