The human Oligophrenin-1 (OPHN1) gene codes for the OPHN1 protein, which is a Rho-GTPase-activating protein that stimulates GTP hydrolysis of members of the Rho family. These Rho proteins play an important role in signal transduction cascades, especially in spine morphogenesis and synapse development. One of these Rho proteins, RhoA, is especially important in the growth and stabilization of dendritic spines. Apart from its role in dendritic spine maturation, OPHN1 has also been shown to play a critical role in the activity-dependent maturation and plasticity of excitatory synapses by controlling their structural and functional stability. In fact, mice deficient in OPHN1 have been shown to have immature dendritic spines, altered synaptic function, ventricular enlargement, and impaired spatial memory.
Mutations in the OPHN1 gene result in a syndromic form of X-linked Mental Retardation, characterized by cerebellar hypoplasia and variable dysmorphic features.