Table 1.

Functional effects of mutations affecting the N-terminus of Shank3, the upper graphic shows the domain structure of Shank3, and lists the missense mutations found in autistic patients which affect the N-terminal part of the protein.

Alteration	References	Inheritance	Domain	Effect on mol. interactions	Effect on dendritic spines	Effect on synaptic signaling
R12C	Durand et al., 2007	Mother (social phobia)	SPN	Ras: reduced Intramolecular: none	Density: moderate reduction Morphology: no effect F-actin: moderate reduction	Trans-synaptic: disrupted Support of mGluR5 pathway: disrupted Inhibition of integrin: lost
L68P	Gauthier et al., 2009	Father (epilepsy)	SPN	Ras: lost Fodrin: up (ns) Sharpin: up Intramolecular: lost	Density: no effect	Inhibition of integrin: lost
P141A	Boccuto et al., 2013	de novo	Ank	n.d.	n.d.	n.d.
A198G	Durand et al., 2007	Mother (healthy)	Ank	n.d.	n.d.	n.d.
R300C	Durand et al., 2007	Mother (healthy)	Ank	Fodrin: none Sharpin: up	Density: moderate reduction Morphology: no effect F-actin: moderate reduction	Trans-synaptic: disrupted
Q321R	Moessner et al., 2007	de novo	Ank	Fodrin: none Sharpin: up	Density: moderate reduction Morphology: shorter spines with larger heads F-actin: no effect	Trans-synaptic: disrupted
S341L	Moessner et al., 2007	Father (healthy)	Ank	n.d.	n.d.	n.d.

N.d, not determined; ns, the observed effect was not statistically different from WT.