In L-type calcium channels, the α1c subunit forms the transmembrane pore, and directly interacts with the intracellular β2 subunit. 31 The β2 subunit also antagonizes an endoplasmic reticulum retention motif on the α1c subunit to facilitate transport to the plasma membrane. 32Additional genes with genome-wide significant evidence were implicated based on membership in a proteomic network centered on Cav2 (reference 33): the protein products of ACTR1A (α-centractin), the divalent metal cation transporter CNNM2 (P=3.7×10−13, chr10:103,009,986-105,512,924), and CACNB2. A broad genomic region containing the calcium binding protein troponin C (TNNC1) also met genome-wide significance (P=1.1×10−8) as well as three calcium homeostasis modulator genes (CALHM1, CALHM2,and CALHM3 in same chr10 region as CNNM2).
