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| Gene | STK11 |
| Variant | F354L |
| Impact List | missense |
| Protein Effect | loss of function - predicted |
| Gene Variant Descriptions | STK11 F354L lies within the C-terminal domain of the Stk11 protein (PMID: 23612973). F354L results in kinase activity similar to wild-type Stk11 in an in vitro assay and Stk11-dependent Tp53-mediated transcriptional activity similar to wild-type in a reporter assay (PMID: 34849607, PMID: 39934475), and does not disrupt Stk11 autophosphorylation or growth suppression by Stk11, but results in decreased Ampk phosphorylation and increased mTOR signaling, and alters cell polarization in culture (PMID: 15800014), and therefore, is predicted to lead to a loss of Stk11 protein function. |
| Associated Drug Resistance | |
| Category Variants Paths |
STK11 mutant STK11 inact mut STK11 F354L |
| Transcript | NM_000455.5 |
| gDNA | chr19:g.1223124T>C |
| cDNA | c.1060T>C |
| Protein | p.F354L |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_000455.4 | chr19:g.1223124T>C | c.1060T>C | p.F354L | RefSeq | GRCh38/hg38 |
| XM_005259617 | chr19:g.1223124T>C | c.1060T>C | p.F354L | RefSeq | GRCh38/hg38 |
| XM_005259618.3 | chr19:g.1223124T>C | c.1060T>C | p.F354L | RefSeq | GRCh38/hg38 |
| NM_001407255.1 | chr19:g.1223124T>C | c.1060T>C | p.F354L | RefSeq | GRCh38/hg38 |
| XM_005259618 | chr19:g.1223124T>C | c.1060T>C | p.F354L | RefSeq | GRCh38/hg38 |
| NM_000455.5 | chr19:g.1223124T>C | c.1060T>C | p.F354L | RefSeq | GRCh38/hg38 |
| XM_005259617.3 | chr19:g.1223124T>C | c.1060T>C | p.F354L | RefSeq | GRCh38/hg38 |
| NM_000455 | chr19:g.1223124T>C | c.1060T>C | p.F354L | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| STK11 F354L | triple-receptor negative breast cancer | predicted - sensitive | Everolimus + Exemestane | Case Reports/Case Series | Actionable | In a clinical case study, Afinitor (everolimus) in combination with Aromasin (exemestane) resulted in complete response ongoing for 14 months in a patient with metastatic triple-receptor negative breast cancer harboring STK11 F354L (PMID: 28550065). | 28550065 |