Potassium channel tetramerization domain containing 7 (KCTD7)

Potassium channel tetramerization domain containing 7 (KCTD7) is a widely expressed neuronal protein encoded by the KCTD7 gene. KCTD7 is a member of the potassium channel tetramerization domain-containing protein family, structurally characterized by an N-terminal BTB/POZ domain homologous to the T1 domain of voltage-gated potassium channels, suggesting a role in protein-protein interactions and multimerization[1][2]. While not itself a canonical potassium channel, KCTD7 modulates potassium conductance—either directly influencing potassium fluxes or indirectly by regulating the membrane expression levels of potassium channels—thereby hyperpolarizing neuronal membranes and stabilizing resting potential[1][2][3]. KCTD7 is localized at the plasma membrane in neurons, particularly in hippocampal neurons, deep cortical layers, and cerebellar Purkinje cells[1][2]. In addition to its role in neuronal excitability, KCTD7 interacts with Cullin-3 (CUL3), positioning it as an adaptor within the ubiquitin ligase complex, and is implicated in targeted protein degradation and maintenance of proteostasis[2][3]. KCTD7 also regulates the function of the neuronal glutamine transporter SAT2 (SLC38A2), affecting neurotransmitter glutamate synthesis[1]. Loss-of-function mutations in KCTD7 are associated with progressive myoclonic epilepsy-3 (EPM3), a devastating early-onset epilepsy syndrome featuring therapy-resistant seizures, cognitive and motor regression, and sometimes overlapping features with neuronal ceroid lipofuscinosis (CLN14)[1][3]. Disease-associated variants disrupt KCTD7’s membrane localization, impair potassium fluxes, and perturb glutamine transport, leading to abnormal neuronal depolarization, pathological discharges, and neurodegeneration[1]. The protein’s dual roles in modulating neuronal excitability and maintaining intracellular proteostasis highlight its importance in both electrical signaling and cellular homeostasis in the central nervous system[1][3].

Other names

CLN14EPM3FLJ32069BTB/POZ domain-containing protein KCTD7potassium channel tetramerisation domain containing 7KCTD7