CALCA

CALCA is a human gene that encodes two related peptides, calcitonin and alpha-calcitonin gene-related peptide (alpha-CGRP), produced by alternative splicing of the preprocalcitonin transcript. In humans, calcitonin is primarily expressed in thyroid C cells, while alpha-CGRP is produced by neurons in the peripheral and central nervous systems.

Gene expression and products: The CALCA gene is transcribed into a single precursor that is differentially processed to yield either calcitonin or alpha-CGRP depending on tissue context. The two products belong to the calcitonin gene family and have distinct physiological roles, despite originating from the same genetic locus.

Physiological roles: Calcitonin participates in calcium homeostasis by inhibiting osteoclast-mediated bone resorption and promoting calcium excretion by the kidneys. Alpha-CGRP is a potent neuropeptide that causes vasodilation and modulates nociceptive signaling, with a well-established role in migraine pathophysiology. The peptides are generated from the CALCA precursor by tissue-specific proteolytic enzymes, such as prohormone convertases.

Clinical relevance: The CGRP signaling axis is a therapeutic target for migraine, with several CGRP receptor antagonists and anti-CGRP antibodies approved for prevention. Calcitonin and its analogs have been used to treat osteoporosis and related calcium disorders, though their clinical use has declined with the availability of other therapies. Procalcitonin, another CALCA-derived peptide, is widely used as a biomarker of bacterial infection and sepsis.

See also: CALCB, calcitonin, CGRP, calcitonin receptor-like receptor, receptor activity-modifying protein 1.