CACNB2

CACNB2 is a human gene that encodes the beta-2 subunit of L-type voltage-gated calcium channels. The beta subunits (CACNB1-4) are cytoplasmic modulators that associate with the pore-forming alpha1 subunits (CACNA1 family) and regulate trafficking, surface expression, and gating properties.

The beta-2 subunit binds to the alpha1 subunit's AID (alpha interaction domain) and is involved in accelerating channel trafficking to the plasma membrane and in shifting voltage dependence of activation and inactivation to more hyperpolarized potentials. The protein contains SH3 and guanylate kinase–like (GK) domains characteristic of the voltage-gated calcium channel beta family. There are multiple transcript variants coding for different isoforms, with tissue-specific expression, including heart and brain.

A key role of CACNB2 is to modulate L-type calcium current (ICa,L) through Cav1.2 (CACNA1C) and Cav1.3 (CACNA1D) channels, influencing excitation-contraction coupling in cardiac myocytes and calcium signaling in neurons. Beta-2–containing channels often show enhanced surface expression and altered kinetics compared to channels lacking beta-2.

Genetic variation in CACNB2 has been reported in association with cardiac arrhythmias and neuropsychiatric conditions in some studies, though functional validation is variable and the clinical significance is not fully established.

In summary, CACNB2 encodes a key auxiliary protein that regulates the trafficking and biophysical properties of L-type calcium channels, contributing to calcium-dependent signaling across cardiac and nervous systems.