Voltage-dependent calcium channel gamma-3 subunit

CACNG3 encodes the voltage-dependent calcium channel gamma-3 subunit, a regulatory protein that modulates glutamate receptor trafficking and function. It promotes AMPA receptor targeting to cell membranes and synapses while slowing their rates of activation, deactivation, and desensitization. The protein also stabilizes voltage-dependent calcium channels in an inactivated state (UniProt: O60359).

CACNG3 is expressed in the brain and participates in excitatory synaptic transmission through modulation of ionotropic glutamate signaling. No baseline disease associations are documented in UniProt, though altered expression of genes regulating synaptic calcium signaling has been implicated in neuropsychiatric conditions.

CACNG3 is downregulated in Alzheimer's disease brain tissue. Analysis of post-mortem AD brain versus age-matched controls using TMT-labeled proteomics across four subcellular fractions revealed a mean log2 fold-change of −0.65 (Chaparral AD proteomics). This reduction is consistent with synaptic dysfunction observed in AD pathology, as impaired AMPA receptor regulation and calcium channel modulation may contribute to excitatory imbalance in degenerating neurons.