IQ motif and Sec7 domain-containing protein 3 (IQSEC3)

IQ motif and Sec7 domain-containing protein 3 (IQSEC3) is a member of the Arf guanine nucleotide exchange factor (GEF) family, specifically acting for ARF6. IQSEC3 is highly localized to inhibitory synapses in the brain, where it directly interacts with gephyrin, a major scaffold protein essential for inhibitory synaptic structure. Its primary function is to promote inhibitory synapse formation through its Arf-GEF catalytic activity, and it is critical for clustering and maintenance of gephyrin at these synapses[1][2][4]. Deficiency or disruption of IQSEC3 leads to decreased gephyrin cluster size and mismatching of postsynaptic components with presynaptic terminals, impacting GABAergic neurotransmission[1][2][3]. Perturbations in IQSEC3 have been associated with neurodevelopmental disorders, particularly non-syndromic X-linked intellectual disability, and potentially with neural tumors[4]. IQSEC3 belongs to a protein family including IQSEC1 and IQSEC2, but is functionally distinct in being specifically tied to GABAergic inhibition and inhibitory postsynaptic density development[1][2].

Other names

IQ motif and Sec7 domain ArfGEF 3KIAA1110MGC30156BRAG3SynArfGEF