SMO activating mutation (Smoothened)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-SMO |
|---|---|
| Type | Biomarker |
| Aliases | SMO mutationАктивуюча мутація SMO (Smoothened) |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESMO-SARCOMA-2024 SRC-NCCN-SKIN-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "multiple", "functional_impact": "activating", "gene": "SMO", "variant_type": "missense activating"} |
| Measurement | MethodTumor NGS panel (DNA-based); common variants: W535L, L412F, Q477E, S533N |
| Actionability lookup | {"gene": "SMO", "variant": "activating_mutation"} |
| Related biomarkers | BIO-PTCH1 |
Notes
SMO (Smoothened) is a G-protein-coupled receptor that transmits Hedgehog (HH) signaling. Normally suppressed by PTCH1; activated when PTCH1 loses its inhibitory function (whether via PTCH1 loss-of-function or SMO gain-of-function mutation). SMO activating mutations (~10–20% of BCCs) and PTCH1 loss-of-function (~90% of BCCs) both result in constitutive HH pathway activation. Vismodegib and sonidegib are SMO antagonists — they bind the SMO transmembrane domain and block downstream HH signaling (GLI1/2 repression). In practice, BCC HHI therapy does not require pre-testing for SMO vs PTCH1 mutation — all BCCs have HH pathway activation. SMO mutations also occur in sporadic medulloblastoma (SHH subtype) and rarely in other tumors. Resistance: secondary SMO mutations (D473H most common) emerge during vismodegib therapy, driving acquired resistance. Sonidegib may be active in some vismodegib-resistant D473H mutants.
Used By
Actionability
BMA-SMO-BCC- Hedgehog (HH) pathway inhibitors — vismodegib (Erivedge, FDA 2012) and sonidegib (Odomzo,...
Biomarker
BIO-PTCH1- PTCH1 loss-of-function mutation (Patched-1)
Diseases
DIS-BCC- Basal cell carcinoma (BCC)
Indications
IND-BCC-1L-SONIDEGIB- IND-BCC-1L-SONIDEGIB