IQ motif and Sec7 domain-containing protein 2 (IQSEC2)

IQ motif and Sec7 domain-containing protein 2 (IQSEC2) is a synaptic enzyme predominantly expressed in the brain and encoded by the X-linked IQSEC2 gene. It acts as a guanine nucleotide exchange factor (GEF) specific for the ADP-ribosylation factor (Arf) family of small GTPases, most specifically Arf6. The protein contains multiple functional domains, including an IQ domain (calmodulin-binding), a Sec7 domain (catalyzes GDP-GTP exchange), a pleckstrin homology (PH) domain (guides localization and membrane interaction), a coiled-coil domain (self-association), a proline-rich domain (protein-protein interaction), and a PDZ-binding motif (linking to postsynaptic density scaffolding proteins). IQSEC2 orchestrates synaptic plasticity, dendritic spine morphogenesis, and membrane trafficking by relaying calcium-calmodulin and NMDA receptor signals to cytoskeletal reorganization and receptor dynamics. Mutations in IQSEC2 are associated with X-linked intellectual disability, epilepsy, and autism, with pathogenic variants disrupting synapse structure and function, resulting in severe developmental encephalopathies.

Other names

KIAA0522BRAG1IQ-ArfGEFBrefeldin A resistant Arf-guanine nucleotide exchange factor 1MRX1MRX18MRX78XLID1

Not applicable; drugs do not directly target IQSEC2. For antiepileptic treatments in patients with IQSEC2 mutations, the mechanism relates to general modulation of neuronal excitability, not direct interaction with the target.