ARHGEF9 and startle disease

I was investigating interactions between enzymes GSK3b and Gephyrin (responsible for assembly of GABA and glycine receptors; and also for synthesis of Molybdenum cofactor), when I found a peculiar protein with ugly name ARHGEF9.

This ARHGEF9 is related to a disorder “Startle disease with epilepsia” with encephalopathy. This led me to this overview of startle-related syndromes.

It seems relevant for our case - the kid is easily startled and has a sequence of tics produced in response to a startling stimuli (even to own thoughts, surprise element, etc).

I’m suspecting poor function of Gephyrin protein, which helps to assemble GABA and glycine receptors, which requires magnesium and completes the last step of MoCo synthesis by inserting molybdenum into the molybdopterin protein.

ARHGEF9 also has a direct role in that process - it promotes Gephyrin clusters, so dysfunction of ARHGEF9 leads directly to insufficient amount of GABA and Glycine receptors, which leads to the startle syndrome.

Anyway, the goal was to share this nice overview - could be useful in case you also deal with impaired startle response.