Table 1.
Genes conferring susceptibility to ASD
| Gene | Description | Related syndrome / co-morbidity |
Approaches | Molecular Function |
|---|---|---|---|---|
| CACNA1C | calcium channel, voltage-dependent, L type, alpha 1C subunit | Timothy | syndrome, WGS | Ion channel |
| CNTN4 | contactin 4 | 3p deletion | CNV, BCA | Synaptic formation and maintenance |
| CNTNAP2 | contactin associated protein-like 2 | Pitt-Hopkins like | BCA, GWAS, targeted NGS, animal model | Synaptic adhesion |
| FMR1 | fragile X mental retardation 1 | fragile X | syndrome, animal model | Regulation of protein synthesis |
| GABRB3 | gamma-aminobutyric acid (GABA) A receptor, beta 3 | Angelman | GWAS, CNV, animal model | Neurotransmitter receptor |
| GRIN2A | glutamate receptor, ionotropic, N-methyl D-aspartate (NMDA) 2A | Epilepsy and speech disorder | GWAS, CNV | Neurotransmitter receptor |
| GRIN2B | glutamate receptor, ionotropic, N-methyl D-aspartate (NMDA) 2B | intellectual disability | GWAS, BCA, WES | Neurotransmitter receptor |
| MBD5 | Methyl-CpG binding domain protein 5 | intellectual disability | CNV, WGS | Epigenetic regulation |
| MECP2 | Methyl CpG binding protein 2 | Rett | syndrome, animal model | Epigenetic regulation |
| NLGN1 | neuroligin 1 | intellectual disability | CNV, animal model | Synaptic adhesion |
| NLGN3 | neuroligin 3 | developmental delay | CNV, WGS, animal model | Synaptic adhesion |
| NLGN4X | neuroligin 4, X-linked | developmentaldelay | CNV, WES | Synaptic adhesion |
| NRXN1 | neurexin 1 | Pitt-Hopkins like | CNV, BCA, animal model | Synaptic adhesion |
| PTEN | phosphatase and tensin homolog | Macrocephaly/autism | syndrome, WES, animal model | Regulation of protein synthesis |
| RELN | Reelin | lissencephaly | GWAS, WES, animal model | Brain architecture |
| SCN2A | sodium channel, voltage-gated, type II, alpha subunit | epilepsy | WES | Ion channel |
| SHANK2 | SH3 and multiple ankyrin repeat domains 2 | intellectual disability | CNV, animal model | Synaptic scaffolding |
| SHANK3 | SH3 and multiple ankyrin repeat domains 3 | 22q13.3del | CNV, animal model | Synaptic scaffolding |
| SYNGAP1 | synaptic Ras GTPase activating protein 1 | intellectual disability | CNV, animal model | Synaptic formation and maintenance |
| TSC1 | tuberous sclerosis 1 | Tubular sclerosis | syndrome | Regulation of protein synthesis |
| TSC2 | tuberous sclerosis 2 | Tubular sclerosis | syndrome, WES, animal model | Regulation of protein synthesis |
| UBE3A | ubiquitin protein ligase E3A | Angelman | syndrome, CNV, animal model | Regulation of protein degradation |
Genes that have been identified in multiple unrelated ASD patients and with a strong genetic and functional evidence are listed in the alphabetical order. The approaches to which the genes are established as ASD susceptible genes are indicated, where “syndrome” indicates that the gene was first identified as the cause of a syndrome related the ASD and “animal model” indicates supporting functional evidence from animal models of the gene.
Abbreviations: BCA, balanced chromosomal abnormality; CNV, copy number variation, GWAS, genome-wide association studies; NGS, next-generation sequencing; WES, whole exome sequencing; WGS, whole genome sequencing.