Synaptic signaling associated with autism spectrum disorder (WP4539)

Homo sapiens

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].


Kristina Hanspers , Egon Willighagen , and Eric Weitz


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Homo sapiens




Pathway Ontology

mTOR signaling pathway

Disease Ontology

autism spectrum disorder


Label Type Compact URI Comment
rapamycin Metabolite chebi:9168
Ca 2+ Metabolite chebi:29108
GTP Metabolite chebi:15996
GDP Metabolite chebi:17552
Ca 2+ Metabolite chebi:29108
AKT2 GeneProduct ncbigene:208 Akt
PRKAA1 GeneProduct ncbigene:5562 AMPK
PRKAA2 GeneProduct ncbigene:5563 AMPK
PRKAB1 GeneProduct ncbigene:5564 AMPK
PRKAB2 GeneProduct ncbigene:5565 AMPK
PRKAG1 GeneProduct ncbigene:5571 AMPK
PRKAG2 GeneProduct ncbigene:51422 AMPK
PRKAG3 GeneProduct ncbigene:53632 AMPK
GRM1 GeneProduct ncbigene:2911 mGluR1
GRIN1 GeneProduct ncbigene:2902 NMDAR
GRIN2A GeneProduct ncbigene:2903 NMDAR
GRIN2B GeneProduct ncbigene:2904 NMDAR
GRIN2D GeneProduct ncbigene:2906 NMDAR
PIK3CA GeneProduct ncbigene:5290 PI3K
PIK3CB GeneProduct ncbigene:5291 PI3K
PIK3CD GeneProduct ncbigene:5293 PI3K
PIK3R3 GeneProduct ncbigene:8503 PI3K
DLG4 GeneProduct ncbigene:1742 PSD95
HRAS GeneProduct ncbigene:3265 Ras
SYNGAP1 GeneProduct ncbigene:8831 SYNGAP1
MTOR GeneProduct ncbigene:2475 mTOR
GSK3B GeneProduct ensembl:ENSG00000082701
MAPK3 GeneProduct ncbigene:5595 ErK
HOMER1 GeneProduct ncbigene:9456 HOMER1
KRAS GeneProduct ncbigene:3845 Ras
NTRK2 GeneProduct ncbigene:4915 TRKB
RPS6KB1 GeneProduct ncbigene:6198 S6K1
EIF4EBP1 GeneProduct ensembl:ENSG00000187840
GRIN3B GeneProduct ncbigene:116444 NMDAR
NF1 GeneProduct ncbigene:4763 NF1
UBE3A GeneProduct ncbigene:7337 UBE3A
BDNF GeneProduct ncbigene:627 BDNF
PTEN GeneProduct ncbigene:5728 PTEN
AKT1 GeneProduct ncbigene:207 Akt
TSC1 GeneProduct ncbigene:7248 TSC1/
NRAS GeneProduct ncbigene:4893 Ras
GRIN3A GeneProduct ncbigene:116443 NMDAR
RHEB GeneProduct ncbigene:6009 Rheb
ARC GeneProduct ncbigene:23237 ARC
CACNA1C GeneProduct ncbigene:775 CACNA1C
CAMK2B GeneProduct ncbigene:816 CaMKII
MAPK1 GeneProduct ncbigene:5594 ErK
GRIN2C GeneProduct ncbigene:2905 NMDAR
TSC2 GeneProduct ncbigene:7249 TSC2
AKT3 GeneProduct ncbigene:10000 Akt
RPTOR GeneProduct ncbigene:57521 Raptor
SHANK3 GeneProduct ensembl:ENSG00000251322 HOMER1
PIK3R2 GeneProduct ensembl:ENSG00000105647 PI3K
PIK3R1 GeneProduct ensembl:ENSG00000145675 PI3K
RHEB GeneProduct ncbigene:6009 Rheb
CAMK4 GeneProduct ensembl:ENSG00000152495 CaMKII


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