Annotation Detail
Information
- Associated Genes
- SMO
- Associated Variants
-
SMO p.Asp473His (p.D473H)
(
ENST00000249373.8 )
SMO p.Asp473His (p.D473H) ( ENST00000249373.8 ) - Associated Disease
- basal cell carcinoma
- Source Database
- CIViC Evidence
- Description
- D473 mutations were identified in 5/30 resistant basal cell carcinomas. Crystal structure indicated this mutation interacts with a water molecule in the ligand binding pocket, putatively altering its interaction with the SMO inhibitor vismodegib. SMO-/- mouse embryonic fibroblasts expressing the SMO D473G mutant maintained hedgehog signaling in the presence of the drug and had IC50 values >40 fold higher than cells expressing wildtype SMO.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/755
- Gene URL
- https://civic.genome.wustl.edu/links/genes/5365
- Variant URL
- https://civic.genome.wustl.edu/links/variants/299
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Basal Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Vismodegib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 25759020
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Vismodegib | Resitance or Non-Reponse | true |