Table 1.
Major genes implicated in autism spectrum disorder (ASD)
| Gene | Name | Cytogenetic location | Protein function | Associated pathologies | References |
|---|---|---|---|---|---|
| CHD8 | Chromodomain helicase DNA‐binding protein 8/autism susceptibility 18 (AUT18) | 14q11.2 | Transcriptional repressor negatively regulates Wnt signaling pathway by binding to beta‐catenin thereby inhibiting binding to TCF4 | ASD | Cotney et al. (2015), Krumm, O'Roak, Shendure, and Eichler (2014), and O'Roak et al. (2012) |
| CNTNAP2 | Contactin‐associated protein‐like 2/autism susceptibility 15 (AUT15) | 7q35–q36 | Protein member of the neurexin superfamily involved in neural and glia interactions and clustering of potassium channels in neurons | Epilepsy, Pitt–Hopkins‐like syndrome 1, ASD | O'Roak et al. (2011) and Toma et al. (2013) |
| CTTNBP2 | Cortactin‐binding protein 2 | 7q31.31 | Modulates the mobility of cortactin in neurons. Regulates spine morphogenesis and synaptic signaling via PP2A complex | ASD | Cross‐Disorder Group of the Psychiatric Genomics Consortium (2013) |
| FMR1 | Fragile X mental retardation protein | Xq27.3 | FMRP is an RNA‐binding protein involved in RNA translation in neurons | Fragile X syndrome, ASD | Devlin and Scherer (2012) and Roberts et al. (2016) |
| MECP2 | Methyl‐CpG‐binding protein 2 | Xq28 | Chromatin‐associated protein that regulates gene transcription. It is required for the maturation of neurons | Rett syndrome, mental retardation X‐linked syndromic 13, autism susceptibility X‐linked 3 | Devlin and Scherer (2012) and Liu and Takumi (2014) |
| NLGN3 | Neuroligin 3 | Xq13.1 | Linked only to glutamatergic postsynaptic proteins | Asperger syndrome susceptibility, autism susceptibility X‐linked 1 | Jamain et al. (2003) |
| NLGN4 | Neuroligin 4 | Xp22.32–p22.31 | Binds to neurexins and localized in dendritic spines | Mental retardation X‐linked, Asperger syndrome susceptibility X‐linked, autism susceptibility X‐linked 2 | Jamain et al. (2003) |
| NRXN1 | Neurexin 1 | 2p16.3 | Neurexins, including NRXN1, are cell surface receptors that bind neuroligins to form a Ca2+‐dependent neurexin/neuroligin complex at synapses in the central nervous system. This complex is required for neurotransmission and is involved in the formation of synaptic connexion | Pitt–Hopkins‐like syndrome 2, schizophrenia, ASD | Anney et al. (2010) and Girirajan et al. (2013) |
| PTEN | Phosphatase and tension homolog | 10q23.31 | Tumor suppressor involved in PI3K signaling pathway and negatively regulates the MAPK pathway | PTEN hamartoma tumor syndrome, macrocephaly, autism | McBride et al. (2010) and O'Roak et al. (2012) |
| SHANK3 | SH3 and multiple ankyrin repeat domains 3 | 22q13.33 | Scaffold protein abundant in postsynaptic excitatory synapses where it organizes receptor signaling (e.g., NMDA receptor, mGluR) | ASD, Phelan–McDermid syndrome, schizophrenia | Durand et al. (2007) and Yi et al. (2016) |
| SYNGAP1 | Synaptic Ras GTPase‐activating protein 1 | 6p21.32 | Ras GTPase‐activating protein that is largely localized in dendritic spines in neocortical pyramidal neurons. Suppresses signaling pathways linked to NMDA receptor (NMDAR)‐mediated synaptic plasticity and AMPA receptor (AMPAR) | Mental retardation, ASD | Pinto et al. (2010) |
| TSC1 | Hamartin | 9q34.13 | Interacts with tuberin to form a complex that inhibits signal transduction to the downstream effectors of the mammalian target rapamycin pathway (mTOR). Implicated in cell proliferation inhibition | Tuberous sclerosis‐1 | Devlin and Scherer (2012) and Liu and Takumi (2014) |
| TSC2 | Tuberin | 16p13.3 | Acts as a chaperone for hamartin protein | Tuberous sclerosis‐2 | Devlin and Scherer (2012) and Liu and Takumi (2014) |