PTPN11 activating mutation (SHP2)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-PTPN11 |
|---|---|
| Type | Biomarker |
| Aliases | PTPN11 / SHP2 mutationАктивуюча мутація PTPN11 (SHP2) |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-COG SRC-NCCN-AML-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "3, 4, 8, 13 (SH2 and PTP domains)", "functional_impact": "activating", "gene": "PTPN11", "variant_type": "missense activating (E76K, D61G, Q79R, A72V, N308D most common)"} |
| Measurement | MethodNGS panel (tumor or germline); common hotspots detectable on standard hematologic panels |
| Actionability lookup | {"gene": "PTPN11", "variant": "activating_mutation"} |
| Related biomarkers | BIO-KRAS-G12C BIO-KRAS-G12D |
Notes
PTPN11 encodes SHP2, a protein tyrosine phosphatase that acts as a positive regulator of the RAS/MAPK pathway. Gain-of-function mutations disrupt autoinhibition, leading to constitutive RAS/ERK activation. Clinical contexts: (1) JMML: somatic PTPN11 mutations in ~35% — the single most common driver. Somatic PTPN11 in JMML carries poor prognosis; germline PTPN11 (Noonan syndrome) may cause a transient self-limiting myeloproliferative process that resolves without HCT. Critical to distinguish somatic vs germline origin — germline PTPN11 is a very different clinical entity. (2) Noonan syndrome (germline): most common cause (~50%); N308D, Q79R, D61G hotspots. Features: short stature, cardiac defects (pulmonary stenosis, HCM), webbed neck. Very low lifetime malignancy risk beyond juvenile myeloproliferative disease. (3) Acute leukemias: PTPN11 mutations in ~7% of AML, ~5% of B-ALL. (4) Solid tumors: ~5% of NSCLC, gastric, colorectal (often co-occurring with KRAS). Therapeutic target: SHP2 inhibitors are in active clinical development — TNO155 (Novartis), RMC-4630 (Revolution Medicines), ERAS-601 (Erasca). Phase I/II trials in solid tumors with KRAS mutations and PTPN11 mutations. SHP2...
Used By
Actionability
BMA-PTPN11-JMML- PTPN11 somatic activating mutations are present in ~35% of JMML cases and define the most...
Diseases
DIS-JMML- Juvenile myelomonocytic leukemia (JMML)