Table 1.
Germline mutations in RASopathies and associated somatic diseases.
| Diseases | Mutated genes | Protein function | Example of somatic hematopoietic disease associated with mutations in each gene |
|---|---|---|---|
| Neurofibromatosis type 1 (NF1) | NF1 | RAS-GAP | JMML, M-group histiocytosis |
| Noonan syndrome (NS) | PTPN11 | Phosphatase | M-group histiocytosis |
| SOS1 | GEF | JMML | |
| KRAS | GTPase | RALD, JMML, ECD, RDD, M-group histiocytosis | |
| NRAS | GTPase | RALD, JMML, ECD, RDD, LCH, M-group histiocytosis | |
| SHOC2 | Scaffolding | ||
| CBL | E3 ubiquitin ligase | JMML, M-group histiocytosis | |
| MAP2K1 | Kinase | ECD, RDD, LCH | |
| Noonan syndrome with multiple lentigines (NSML) | RAF1 | Kinase | ECD |
| PTPN11 | Phosphatase | M-group histiocytosis | |
| Costello syndrome (CS) | HRAS | GTPase | M-group histiocytosis |
| Cardio-facio-cutaneous syndrome (CFC) | KRAS | GTPase | RALD, JMML, ECD, RDD, M-group histiocytosis |
| BRAF | Kinase | ECD, LCH, RDD, M-group histiocytosis, hairy cell leukemia | |
| MAP2K1 | Kinase | ECD, RDD, LCH, M-group histiocytosis | |
| MAP2K2 | Kinase | ECD | |
| Legius syndrome (LS) | SPRED1 | Sprouty-related, EVH1 domain-containing protein 1 (inhibitor of RAS/MAPK activation) | |
| Capillary malformation arteriovenous malformation Syndrome (CM-AVM) | RASA1 | RAS-GAP | |
| Autosomal dominant intellectual disability type 5 | SYNGAP1 | Synaptic RAS-GAP |
Abbreviations: JMML: juvenile Myelo-Monocytic leukemia; RDD: Destombes-Rosai-Dorfman; ECD: Erdheim-Chester disease; LCH: Langerhans cell histiocytosis; RALD: RAS-associated leukoproliferative disease.