Table 1.
Gene mutations related to Small GTPases (Ras family).
| Gene mutations | Related disease | Proteins | Pathway/mechanism | References |
|---|---|---|---|---|
| PTPN11 | NS | SHIP2: Protein tyrosine phosphatase | Increased RAS/MAPK | Siegfried et al., 2017 |
| PTPN11 | NS-ML | SHIP2: Protein tyrosine phosphatase | Increased AKT/mTOR | Tajan et al., 2015 |
| SOS1 | NS | Son of sevenless homolog 1 | Increased RAS/MAPK, Rac, and Stat3 | Van Trier et al., 2017 |
| RAF1 | NS | v-Raf-1 murine leukemia viral oncogene homolog 1 | Increased RAS/MAPK | Yin et al., 2017 |
| RAF1 | NS-ML | v-Raf-1 murine leukemia viral oncogene homolog 1 | ||
| KRAS | NS | V-Ki-Ras2 Kirsten rat sarcoma viral oncogene homolog | Increased RAS/MAPK | Tartaglia et al., 2011 |
| KRAS | CFCS | |||
| NRAS | NS | Neuroblastoma Ras viral (V-Ras) oncogene homolog | Increased RAS/MAPK | Ekvall et al., 2015 |
| SHOC2 | NS | soc-2 suppressor of clear homolog | SHOC2-MRAS-PP1 complex positively regulates RAF activity | Young et al., 2018 |
| SHOC2 | NS-LAH | soc-2 suppressor of clear homolog | ||
| BRAF | NS | Serine/Threonine-Protein Kinase B-Raf | Increased RAS/MAPK | Tartaglia et al., 2011 |
| BRAF | CFCS | Serine/Threonine-Protein Kinase B-Raf | Increased RAS/MAPK, Decreased p38 and AKT | Tartaglia et al., 2011 |
| RIT1 | NS | Ras-Like Without CAAX 1 | Increased RAS/MAPK | Aoki et al., 2013 |
| RRAS | NS | Related Ras viral (R-Ras) Oncogene Homolog | Related RAS Viral (R-Ras) Oncogene Homolog; Increased RAS/MAPK | Flex et al., 2014 |
| MAP3K8 | NS | RAS/MARK pathway | Increased RAS/MAPK | Tidyman and Rauen, 2016a |
| MEK1 | CFCS | MEK 1: Mitogen-activated protein kinase kinase 1 | Increased RAS/MAPK | Dentici et al., 2009 |
| NF1 | NF-1 | Neurofibromin | PI3K/mTOR/AKT pathway | Arun et al., 2013 |
| SPRED1 | LS | Sprouty-related EVH1 domain containing protein 1 | Increased RAS/MAPK and JAK2 | Hirata et al., 2016 |
| SPRED2 | OCD | Sprouty-related EVH1 domain containing protein 2 | Loss of SPRED2 | Ullrich et al., 2018 |
| HRAS | CS | Harvey rat sarcoma viral oncogene homolog | Increased RAS/MAPK | Bertola et al., 2017 |
| RIT2 (rs12456492) | Parkinson’s disease | CD33 | rs12456492 polymorphism is associated with increased CD33 expression | Liu et al., 2015 |
| RIT2 (rs12456492) | Essential tremor | – | – | Emamalizadeh et al., 2017 |
| RIT2 (rs16976358) | Autism spectrum disorder | Regulatory motif of the SOX transcription factor | rs16976358 variant | Hamedani et al., 2017 |
| RIT2 (rs16976358) | Schizophrenia | – | CNV | Rees et al., 2014; Tansey et al., 2016 |
| RIT2 (rs16976358) | Bipolar disorder | – | – | Emamalizadeh et al., 2017 |
| RIT2 (rs4130047) | Autism spectrum disorder | – | – | Hamedani et al., 2017 |
NS, Noonan syndrome; NS-ML, Noonan syndrome with multiple lentigines; NS-LAH, Noonan-like syndrome disorder with loose anagen hair; CS, Costello syndrome; CFCS, Cranio-facio-cutaneous syndrome; LS, Legius syndrome; OCD, Obsessive compulsive disorder; NF-1, Type 1 neurofibromatosis; CNVs, Copy number variations.