Table 1. Synaptic Regulators of RhoGTPase Signaling.
| RhoGTPase Target | Proteome ID | Known Synaptic Function(s) | Neuronal Disease Association | Chromosome Location | Autism-Associated Copy Number Variants* | |
|---|---|---|---|---|---|---|
| GEFs | ||||||
| FRABIN (FDG4) | Cdc42 [53] | [28] | • Unknown | Mutated in Charcot-Marie Tooth [37,38] | 12p11.21 (32,655,040–32,798,983) |
• Deletion in Autism with Scoliosis Case [54] • 6 Duplications [55] • 4 Duplications and 1 Deletion [56] • 1 Reported Duplication in each publication [57,58] • 1 Deletion [54] |
| ARHGEF9 (COLLYBISTIN) | Cdc42 [59] | [31] | • Promotes inhibitory synapse formation through gephyrin clustering [26,27] | X-linked Mental Retardation [60,61] | Xq11.1 (62,854,848–63,005,426) | • 2 Duplications and 1 Deletion [56] |
| ARHGEF7 (β-PIX) | Rac [62] | [28,31] |
• Promotes synaptic vesicle recruitment [63] • Increases synaptic Rac activity, resulting in increased dendritic protrusions [5,23] |
Mutations in β-PIX isoform (on X Chromosome) result in non-syndromic mental retardation [64] | 13q34 (111,767,624–111,958,081) |
• 24 Deletions and 1 Duplication [65] • 16 Deletions and 16 Duplications [56] • 1 Deletion and 1 Duplication [55] • 1 Reported Deletion in each publication [57,58,66] • 1 Duplication and 1 Unspecified CNV Reported [67] • 1 Duplication [19] |
| VAV2 | Rac (can also regulate Cdc42 and RhoA in vitro) [68] | [31] |
• Promotes dendritic development [69,70] • Activated in Response to BDNF and increases spine head size [71] |
None Reported | 9q34.1 (136,627,016–136,857,726) |
• 12 Duplications [56] • 1 Reported Duplication in each publication [72,73] • 1 Deletion [74] • 1 Deletion [19] |
| GAPs | ||||||
| ARHGAP23 | • unknown | [32] | • Unknown | None Reported | 17q12 (36,584,719–36,668,627) |
• 1 Reported Duplication in each publication [56,75] • 1 Duplication and 1 Deletion [65] |
| OLIGOPHRENIN-1 | RhoA | N/A |
• Regulates activity-dependent strengthening of excitatory synapses through interaction with Homer [76] • Regulates spine length and maturation [15,18] |
X-linked Mental Retardation [16] | Xq12 (67262186–67653299 |
• 36 Duplications and 11 Deletions [56] • 3 Duplications [77] • 1 Reported Duplication in each publication [78–80] • 1 Mosaic Duplication [74] • 1 Reported Deletion in each publication [57,81] |
| GDIs | ||||||
| ARHGDIA (RHOGDI α) | RhoGTPases | N/A | • Unknown | None, but is mutated in Nephrotic Syndrome [82] | 17q25.3 (79825597–79829282) |
• 3 Duplications [65] • 1 Duplication [83] • 1 Duplication [19] |
| ARHGDIB (RHOGDI β) | RhoGTPases | N/A | • Unknown | None Reported | 12p12.3 (15094950–15114562) |
• 4 Duplications and 1 Deletion [56] • 2 Reported Deletions in each publication [84,85] • 1 Deletion [86] • 1 Reported Duplication in each publication [57,58,73,87] |
| ARHGDIG (RHOGDI γ) | RhoGTPases | N/A | • Unknown | None Reported | 16p13.3 (330606–333003) |
• 13 Duplications and 1 Deletion [65] • 5 Duplications and 4 Deletions [56] • 1 Reported Deletion in each publication [55,88–90] • 1 Duplication [57] |
* In most cases, CNVs were identified through SFARI gene and include CNV reports that include all or part of the gene. In certain cases, Autism is not the primary patient diagnosis.