Synaptic signaling pathways associated with autism spectrum disorder (WP4539)

Synaptic signaling pathways associated with autism spectrum disorder (ASD). Changes in mTOR activation is believed to be a risk factor for ASD. mTOR is regulated by the TCS1/2 complex, and several signaling pathways upstream of TSC1/2 positively or negatively regulate this complex, including PI3K–AKT, Ras–ERK, LKB1–AMPK and Wnt–GSK3β pathways. The mTOR pathway is also regulated by the brain‐derived neurotrophic factor (BDNF), which plays a key role in the development and the plasticity of the central nervous system and is considered a risk factor for ASD. Increased levels of BDNF concentration have been observed in the serum and brain of patients with ASD. mTOR is a key modulator of protein synthesis and thus blocks the activation of cell autophagy and promotes cell proliferation, growth, and differentiation. Proteasome activity is also affected by neuronal activity, via increased expression of UBE3A through transcription factor MEF2, which leads to the internalization of AMPA-R. Variations in the Calcium-channel CACNA1C are also associated with ASD and [ Timothy Syndrome]. Adapted from figure 1 from [ Daghsni et al].
last edited


Khanspers and Egonw

Cited In


Homo sapiens




Pathway Ontology: mTOR signaling pathway

Disease Ontology: autism spectrum disorder


Label Type Compact Identifier
AKT2 GeneProduct ncbigene:208
PRKAA1 GeneProduct ncbigene:5562
PRKAA2 GeneProduct ncbigene:5563
PRKAB1 GeneProduct ncbigene:5564
PRKAB2 GeneProduct ncbigene:5565
PRKAG1 GeneProduct ncbigene:5571
PRKAG2 GeneProduct ncbigene:51422
PRKAG3 GeneProduct ncbigene:53632
GRM1 GeneProduct ncbigene:2911
GRIN1 GeneProduct ncbigene:2902
GRIN2A GeneProduct ncbigene:2903
GRIN2B GeneProduct ncbigene:2904
GRIN2D GeneProduct ncbigene:2906
PIK3CA GeneProduct ncbigene:5290
PIK3CB GeneProduct ncbigene:5291
PIK3CD GeneProduct ncbigene:5293
PIK3R3 GeneProduct ncbigene:8503
DLG4 GeneProduct ncbigene:1742
HRAS GeneProduct ncbigene:3265
SYNGAP1 GeneProduct ncbigene:8831
MTOR GeneProduct ncbigene:2475
GSK3B GeneProduct ensembl:ENSG00000082701
MAPK3 GeneProduct ncbigene:5595
HOMER1 GeneProduct ncbigene:9456
KRAS GeneProduct ncbigene:3845
rapamycin Metabolite chebi:9168
NTRK2 GeneProduct ncbigene:4915
RPS6KB1 GeneProduct ncbigene:6198
EIF4EBP1 GeneProduct ensembl:ENSG00000187840
Ca 2+ Metabolite chebi:29108
GRIN3B GeneProduct ncbigene:116444
GTP Metabolite chebi:15996
NF1 GeneProduct ncbigene:4763
UBE3A GeneProduct ncbigene:7337
BDNF GeneProduct ncbigene:627
PTEN GeneProduct ncbigene:5728
AKT1 GeneProduct ncbigene:207
TSC1 GeneProduct ncbigene:7248
NRAS GeneProduct ncbigene:4893
GRIN3A GeneProduct ncbigene:116443
RHEB GeneProduct ncbigene:6009
ARC GeneProduct ncbigene:23237
CACNA1C GeneProduct ncbigene:775
CAMK2B GeneProduct ncbigene:816
MAPK1 GeneProduct ncbigene:5594
GRIN2C GeneProduct ncbigene:2905
TSC2 GeneProduct ncbigene:7249
AKT3 GeneProduct ncbigene:10000
GDP Metabolite chebi:17552
RPTOR GeneProduct ncbigene:57521
SHANK3 GeneProduct ensembl:ENSG00000251322
PIK3R2 GeneProduct ensembl:ENSG00000105647
PIK3R1 GeneProduct ensembl:ENSG00000145675
RHEB GeneProduct ncbigene:6009
Ca 2+ Metabolite chebi:29108
CAMK4 GeneProduct ensembl:ENSG00000152495


  1. Daghsni M, Rima M, Fajloun Z, Ronjat M, Brusés JL, M’rad R, et al. Autism throughout genetics: Perusal of the implication of ion channels. Brain Behav. 2018 Aug;8(8):e00978. PubMed Europe PMC Scholia