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| Gene | FGFR2 |
| Variant | K659N |
| Impact List | missense |
| Protein Effect | gain of function |
| Gene Variant Descriptions | FGFR2 K659N (also referred to as K660N from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K659N results in proliferation similar to wild-type Fgfr2 in a competition assay (PMID: 34272467) but confers a gain of function to the Fgfr2 protein as demonstrated by increased autophosphorylation and phosphorylation of downstream targets, Mek and Stat3 (PMID: 23527311), and increased transformation activity in cultured cells (PMID: 34272467). |
| Associated Drug Resistance | |
| Category Variants Paths |
FGFR2 mutant FGFR2 act mut FGFR2 K659N |
| Transcript | NM_000141.5 |
| gDNA | chr10:g.121488000C>G |
| cDNA | c.1977G>C |
| Protein | p.K659N |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_022970.3 | chr10:g.121488003T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| NM_022970.4 | chr10:g.121488003T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| NM_001144913.1 | chr10:g.121488003T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| NM_022970 | chr10:g.121488003T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| XM_017015920.3 | chr10:g.121488054T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| XM_006717708 | chr10:g.121488054T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| NM_000141.5 | chr10:g.121488000C>G | c.1977G>C | p.K659N | RefSeq | GRCh38/hg38 |
| NM_000141 | chr10:g.121488000C>G | c.1977G>C | p.K659N | RefSeq | GRCh38/hg38 |
| XM_006717708.4 | chr10:g.121488054T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| XM_017015920.2 | chr10:g.121488054T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| NM_001144913 | chr10:g.121488003T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| XM_017015920 | chr10:g.121488054T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| XM_006717708.3 | chr10:g.121488054T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| NM_001144913.1 | chr10:g.121488003T>G | c.1977A>C | p.K659N | RefSeq | GRCh38/hg38 |
| NM_000141.4 | chr10:g.121488000C>G | c.1977G>C | p.K659N | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| FGFR2 K659N | Advanced Solid Tumor | predicted - resistant | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 K659N were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
| FGFR2 K659N | Advanced Solid Tumor | predicted - sensitive | Pemigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 K659N were sensitive to treatment with Pemazyre (pemigatinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
| FGFR2 K659N | Advanced Solid Tumor | predicted - sensitive | Futibatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 K659N were sensitive to treatment with Lytgobi (futibatinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
| FGFR2 K659N | Advanced Solid Tumor | predicted - sensitive | Erdafitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 K659N were sensitive to treatment with Balversa (erdafitinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
| FGFR2 K659N | Advanced Solid Tumor | predicted - sensitive | E7090 | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 K659N were sensitive to treatment with E7090 in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
| FGFR2 K659N | Advanced Solid Tumor | predicted - sensitive | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 K659N were sensitive to treatment with Truseltiq (infigratinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
| FGFR2 K659N | Advanced Solid Tumor | predicted - sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 K659N were sensitive to treatment with Fexagratinib (AZD4547) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |