Table 1. Summary of Genes Associated with NDDs That May Be Involved in Steps of Synapse Assembly.
| Step in synapse assembly | Gene | Chromosome | Protein function | Alleles | NDD diagnosed | Prevalence | Reference |
|---|---|---|---|---|---|---|---|
| Neuronal contact | NLGN3 | Xq13.1 | Synaptic CAM | Mutations | ASD | 0.26% (1774) [2] | Jamain et al (2003); Glessner et al (2009) |
| NLGN4X | Xp22 | Synaptic CAM | Mutations | ASD, ID, TS | 2.65% (498) [2] | Jamain et al (2003) | |
| NLGN1 | 3q26.31 | Synaptic CAM | CNV | ASD | *5.01% (2195) [1] | Glessner et al (2009) | |
| NRXN1 | 2p16.3 | Synaptic CAM | CNV, mutations, microdel. | ASD, SCZ | 0.42% (2380) [3] | Awadalla et al (2010); Reichelt et al (2012) | |
| CADM1 | 11q23.2 | Synaptic CAM | Mutations | ASD | 1.00% (194) [1] | Zhiling et al (2008) | |
| Transport | MAPT | 17q21.31 | Microtubule associated | CNV | ASD, SCZ, ID | 0.14% (14270) [2] | Rovelet-Lecrux et al (2012) |
| KIF17 | 1p36.12 | Motor protein | Nonsense mutation | SCZ | 0.29% (710) [2] | Awadalla et al (2010); Tarabeux et al (2010) | |
| GSK3B | 3q13.33 | Kinase | SSM | SCZ | NA (459) [1] | Blasi et al (2013) | |
| Recruitment and maintenance | SHANK1 | 19q13.3 | Scaffolding protein | Microdeletions | ASD | 0.31% (1614) [2] | Sato et al (2012) |
| SHANK2 | 11q13.2 | Scaffolding protein | Deletions, SSM | ASD, ID | 3.41% (851) [2] | Berkel et al, (2010); Leblond et al (2012) | |
| SHANK3 | 22q13.3 | Scaffolding protein | Mutations | ASD, SCZ, mild ID | 0.74% (1466) [2] | Awadalla et al, (2010) | |
| CDK5R1 | 17q11.2 | Kinase regulator | Mutations | ID | 1.00% (100) [1] | Venturin et al (2006) | |
| CASK | Xp11.4 | Scaffolding protein | Mutations | XLMR, MIC-PCH | **4.43% (557) [3] | Hackett et al (2009); Najm et al (2008) |
Abbreviations: ASD, autism spectrum disorder; CAM, cell adhesion molecule; CNV, copy number variation; ID, intellectual disability; MIC-PCH, microcephaly and disproportionate pontine cerebellar hypoplasia; NA, not available; SSM, splice site mutation; TS, Tourette’s syndrome; XLMR, X-linked mental retardation.
Prevalence is quantified as the average percentage of the sample's affected population with the identified alleles. The total sample size and the number of studies are in round and square parentheses, respectively. *NLGN1 CNVs were detected in control populations, resulting in an odds ratio of only 1.47; **CASK mutations were determined using a very specific disease population, XLMR and MIC-PCH, and thus does not represent the prevalence in the NDD population.