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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

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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
XM_006717708 chr10:g.121488054T>G c.1977A>C p.K659N RefSeq GRCh38/hg38
NM_022970 chr10:g.121488003T>G c.1977A>C p.K659N RefSeq GRCh38/hg38
XM_006717708.4 chr10:g.121488054T>G c.1977A>C p.K659N RefSeq GRCh38/hg38
XM_017015920 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_000141.4 chr10:g.121488000C>G c.1977G>C p.K659N RefSeq GRCh38/hg38
NM_001144913 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
XM_006717708.3 chr10:g.121488054T>G c.1977A>C p.K659N RefSeq GRCh38/hg38
NM_022970.3 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
NM_000141 chr10:g.121488000C>G c.1977G>C p.K659N RefSeq GRCh38/hg38
XM_017015920.2 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_022970.4 chr10:g.121488003T>G c.1977A>C p.K659N RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 AZD4547 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 - 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 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 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 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 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