Therefore, gain-of-function germline mutations in genes, such as NRAS (NRAS Proto-Oncogene, GTPase), KRAS (KRAS Proto-Oncogene, GTPase), CBL (Cbl Proto-Oncogene), PTPN1 (Protein Tyrosine PhosphataseNon-Receptor Type 11), and SH2B3 (SH2B Adaptor Protein 3), result in aberrant activation of corresponding signaling pathways, resulting in myeloid neoplasms, such as Juvenile myelomonocytic leukemia (JMML) or myeloproliferative neoplasm (MPN). The gene discussed is SH2B3; the disease is juvenile myelomonocytic leukemia.