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FGFR2 N549K - Gene Variant Detail

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Gene FGFR2
Variant N549K
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions FGFR2 N549K lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N549K confers a gain of function to the Fgfr2 protein resulting in a growth advantage relative to wild-type Fgfr2 in a competition assay, increased transformation activity in cultured cells (PMID: 34272467), oncogenic transformation in culture (PMID: 18552176, PMID: 17803937, PMID: 29533785) and increased MAPK pathway signaling in cultured cells (PMID: 19147536).
Associated Drug Resistance Y
Category Variants Paths

FGFR2 mutant FGFR2 act mut FGFR2 N549K

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Transcript NM_000141.5
gDNA chr10:g.121498520A>C
cDNA c.1647T>G
Protein p.N549K
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001144915.2 chr10:g.121488063A>C c.1647T>G p.N549K RefSeq GRCh38/hg38
NM_001144919.2 chr10:g.121488066G>C c.1647C>G p.N549K RefSeq GRCh38/hg38
NM_001144915 chr10:g.121488063A>C c.1647T>G p.N549K RefSeq GRCh38/hg38
NM_023029.2 chr10:g.121488063A>C c.1647T>G p.N549K RefSeq GRCh38/hg38
NM_023029.2 chr10:g.121488063A>C c.1647T>G p.N549K RefSeq GRCh38/hg38
NM_023029 chr10:g.121488063A>C c.1647T>G p.N549K RefSeq GRCh38/hg38
NM_000141.4 chr10:g.121498520A>C c.1647T>G p.N549K RefSeq GRCh38/hg38
NM_000141 chr10:g.121498520A>C c.1647T>G p.N549K RefSeq GRCh38/hg38
NM_001144915.1 chr10:g.121488063A>C c.1647T>G p.N549K RefSeq GRCh38/hg38
NM_001144919 chr10:g.121488066G>C c.1647C>G p.N549K RefSeq GRCh38/hg38
NM_001144919.1 chr10:g.121488066G>C c.1647C>G p.N549K RefSeq GRCh38/hg38
NM_000141.5 chr10:g.121498520A>C c.1647T>G p.N549K RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 K310R FGFR2 N549K endometrial carcinoma sensitive FIIN-1 Preclinical Actionable In a preclinical study, FIIN-1 inhibited proliferation of endometrial carcinoma cell lines harboring FGFR2 N549K and FGFR2 K310R mutations in culture (PMID: 20338520). 20338520
FGFR2 K310R FGFR2 N549K endometrial cancer sensitive Zoligratinib Preclinical Actionable In a preclinical study, Debio 1347 inhibited proliferation of endometrial cancer cells harboring FGFR2 K310R and FGFR2 N549K mutations in culture (PMID: 25169980). 25169980
FGFR2 K310R FGFR2 N549K endometrial carcinoma no benefit RO4987655 Preclinical - Cell culture Actionable In a preclinical study, endometrial carcinoma cells harboring both FGFR2 K310R and N549K were not sensitive to RO4987655 in culture (PMID: 26438159). 26438159
FGFR2 K310R FGFR2 N549K endometrial carcinoma no benefit RO5126766 Preclinical - Cell culture Actionable In a preclinical study, endometrial carcinoma cells harboring both FGFR2 K310R and N549K were not sensitive to RO5126766 in culture (PMID: 26438159). 26438159
FGFR2 K310R FGFR2 N549K endometrial carcinoma no benefit Selumetinib Preclinical - Cell culture Actionable In a preclinical study, endometrial carcinoma cells harboring both FGFR2 K310R and N549K were not sensitive to Selumetinib (AZD-6244) in culture (PMID: 26438159). 26438159
FGFR2 K310R FGFR2 N549K endometrial cancer predicted - sensitive Futibatinib Preclinical - Cell culture Actionable In a preclinical study, Lytgobi (futibatinib) treatment led to inhibition of cell proliferation in an endometrial cancer cell line harboring FGFR2 K310R and FGFR2 N549K in culture (PMID: 32973082). 32973082
FGFR2 K310R FGFR2 N549K endometrial adenocarcinoma sensitive Lirafugratinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lirafugratinib inhibited proliferation of an endometrial adenocarcinoma cell line harboring FGFR2 N549K and FGFR K310R in culture, and led to tumor regression in a cell line xenograft model (PMID: 37270847). 37270847
FGFR2 K310R FGFR2 N549K endometrial adenocarcinoma sensitive Futibatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lytgobi (futibatinib) treatment led to tumor regression in a cell line xenograft model of endometrial adenocarcinoma harboring FGFR2 N549K and FGFR2 K310R (PMID: 37270847). 37270847
FGFR2 I291_Y308del FGFR2 N549K cholangiocarcinoma predicted - resistant Pemigatinib Case Reports/Case Series Actionable In a Phase II trial (FIGHT-207), FGFR2 N549K was identified in the post-progression circulating tumor DNA of a patient with cholangiocarcinoma harboring FGFR2 I291_Y308del who previously responded to Pemazyre (pemigatinib) treatment (PMID: 38710951; NCT03822117). 38710951
FGFR2 C382R FGFR2 N549D FGFR2 N549H FGFR2 N549K FGFR2 V564L cholangiocarcinoma predicted - resistant Pemigatinib Case Reports/Case Series Actionable In a Phase II trial (FIGHT-207), FGFR2 N549K, FGFR2 V564L, FGFR2 N549D, and FGFR2 N549H were identified in the post-progression circulating tumor DNA of a patient with cholangiocarcinoma harboring FGFR2 C382R who previously responded to Pemazyre (pemigatinib) treatment (PMID: 38710951; NCT03822117). 38710951