Table 3.

Upstream regulators of mTORC1 implicated in ASC that act as positive regulators of mTORC1 signaling.

Gene	No. of articles	Average spine density	Spine morphology	Murine social beh.	Ultrasonic vocalizations	Repetitive beh.	Human syndrome	Microcephaly
SHANK3	9	D	Decreased mature and immature spine morphology	Decreased	Decreased	Inc. self grooming and marble burying	Phelan-mcDermid syndrome (PMS)	yes
MECP2	9	D	OE increased immature and decreased mature	Decreased	Altered	Inc. self grooming	Rett syndrome	yes
UBE3A	4	D	Increased immature decreased mature	Increased	Increased	Drecreased marble burying	Angelmans syndrome (AS)	yes
Tbr1	4	D	-	Decreased	Decreased	Increased self grooming	-	yes
CDKL5	1	D	Increased immature (filopodia, thin and stubby) decreased mature mushroom	Decreased	Decreased	Increased digging	CDKL5 defficiency syndrome	yes
RELN	1	D	-	Decreased	Decreased	-	-	yes
DIP2A	1	I	Increased mature (mushroom and stubby) and increased spine width and decreased length	Decreased	Decreased	Increased self grooming	-	-

Loss of these genes typically (with the exception of Dip2A) results in decreased spine density and abnormal social behaviors and increased repetitive behaviors. Spine density is recorded as an mean of the spine density values reported in the hippocampus and/or cortex across several studies. Note that Angelmann’s syndrome in humans is a result of the deletion of the maternal allele of UBE3A while most ASC cases arise from a duplication of UBE3A. References: Fukuda et al. (2005), Dindot et al. (2008), Verpelli et al. (2011), Wang et al. (2011), Wang et al. (2014), Durand et al. (2012), Nguyen et al. (2012), Iafrati et al. (2013), Cochoy et al. (2015), Valluy et al. (2015), Kim et al. (2016), Mei et al. (2016), Okuda et al. (2017), Wang et al. (2017), Wang et al. (2019), Fuchs et al. (2018), Ma et al. (2019), Chen et al. (2020), Darbandi et al. (2020), and Jacot-Descombes et al. (2020).