ABCC9

ABCC9 encodes sulfonylurea receptor 2 (SUR2), a multipass ABC-family protein that regulates ATP-sensitive potassium (KATP) channels. Four SUR subunits associate with four pore-forming Kir6 subunits; potassium crosses Kir6, while SUR2 binds nucleotides and drugs and couples these signals to channel gating. Its nucleotide-binding domains bind ATP/ADP and possess ATPase activity, but SUR2 is not an ATP-driven ion pump. The major C-terminal splice isoforms SUR2A (O60706-1) and SUR2B (O60706-2) differ in their final 42 amino acids and in nucleotide/drug responses. SUR2A commonly partners with Kir6.2 in cardiac and skeletal muscle, whereas SUR2B commonly partners with Kir6.1 in vascular smooth muscle. At the plasma membrane these channels couple metabolic state to potassium conductance, membrane excitability and muscle/vascular responses. Activating ABCC9 variants cause dominant Cantú syndrome; biallelic loss-of-function variants cause an intellectual disability and myopathy syndrome. Short intra-exonic splice products have also been reported in mitochondria, a distinct context from the canonical surface-channel isoforms.

Disorders

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• cardiac_ion_channel_repolarization via Familial Atrial Fibrillation