GNAS activating mutation (Gα_s protein)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-GNAS |
|---|---|
| Type | Biomarker |
| Aliases | GNAS mutation / Gαs activating mutationАктивуюча мутація GNAS (Gα_s протеїн) |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESMO-PANCREATIC-2024 SRC-NCCN-PANCREATIC-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "8 (codon 201: R201C, R201H, R201S) or exon 9 (codon 227: Q227L, Q227R)", "functional_impact": "activating", "gene": "GNAS", "variant_type": "missense activating (R201 mutations impair GTPase activity; Q227L similar mechanism)"} |
| Measurement | MethodTumor NGS (pancreatic cyst fluid cytology + NGS, endoscopic ultrasound-guided fine needle aspiration); standard tissue NGS for other contexts |
| Actionability lookup | {"gene": "GNAS", "variant": "R201"} |
| Related biomarkers | BIO-KRAS-G12C BIO-KRAS-G12D |
Notes
GNAS encodes the Gα stimulatory subunit (Gα_s) that couples G-protein-coupled receptors to adenylyl cyclase. Activating mutations at R201 or Q227 impair intrinsic GTPase activity, leading to constitutive cAMP signaling. Key clinical contexts: (1) Intraductal papillary mucinous neoplasm (IPMN): GNAS R201 mutations in ~40–70% of IPMNs (predominantly main-duct and mixed-type). GNAS mutation in cyst fluid provides evidence of mucinous (vs serous) neoplasm when combined with KRAS mutation and elevated CEA (>192 ng/mL). GNAS alone does not distinguish high-grade from low-grade IPMN. GNAS + KRAS double mutation associated with higher malignant risk (NCCN/IAP guidelines recommend surgical resection more strongly). Used in Pancrasite and other multi-analyte cyst fluid panels. (2) Pancreatic ductal adenocarcinoma (PDAC): GNAS mutations in ~10% — typically arising from IPMN-associated PDAC (mucinous pathway). (3) Fibrous dysplasia / McCune-Albright syndrome: post-zygotic somatic GNAS R201 mutations in a mosaic distribution cause fibrous dysplasia (bone) and, in McCune-Albright, also café-au-lait spots, precocious puberty, and hormone hypersecretion. Not oncology- relevant unless malignant tr...
Used By
Actionability
BMA-GNAS-IPMN- GNAS R201 mutations are detected in ~40–70% of IPMNs (predominantly main-duct and mixed-t...