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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 |
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_000141.5 | chr10:g.121498520A>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_001144915.2 | chr10:g.121488063A>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_001144919.1 | chr10:g.121488066G>C | c.1647C>G | p.N549K | RefSeq | GRCh38/hg38 |
NM_023029.2 | 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_023029 | 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_000141.4 | chr10:g.121498520A>C | c.1647T>G | p.N549K | RefSeq | GRCh38/hg38 |
NM_001144915 | chr10:g.121488063A>C | c.1647T>G | p.N549K | RefSeq | GRCh38/hg38 |
NM_000141 | chr10:g.121498520A>C | c.1647T>G | p.N549K | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR2 N549K | Advanced Solid Tumor | resistant | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 N549K were resistant to treatment with AZD4547 in culture (PMID: 34272467). | 34272467 |
FGFR2 N549K | Advanced Solid Tumor | resistant | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 N549K were resistant to treatment with Truseltiq (infigratinib) in culture (PMID: 34272467). | 34272467 |
FGFR2 N549K | endometrial cancer | decreased response | Dovitinib | Preclinical | Actionable | In a preclinical study, Dovitinib (TKI258) did not potently inhibit proliferation of endometrial cancer cell lines harboring FGFR2 N549K in cell culture (PMID: 22238366). | 22238366 |
FGFR2 N549K | Advanced Solid Tumor | resistant | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 N549K were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
FGFR2 N549K | endometrial cancer | resistant | Nintedanib | Preclinical | Actionable | In a preclinical study, Ofev (Nintedanib) did not inhibit growth of endometrial cancer cells harboring FGFR2 N549K in cell culture (PMID: 22238366). | 22238366 |
FGFR2 N549K | endometrial cancer | sensitive | Ponatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited growth of endometrial cancer cells harboring FGFR2 N549K in culture and in cell line xenograft models (PMID: 22238366). | 22238366 |
FGFR2 N549K | endometrial carcinoma | no benefit | RO4987655 | Preclinical - Cell culture | Actionable | In a preclinical study, endometrial carcinoma cells harboring FGFR2 N549K were not sensitive to RO4987655 in culture (PMID: 26438159). | 26438159 |
FGFR2 N549K | endometrial carcinoma | no benefit | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, endometrial carcinoma cells harboring FGFR2 N549K were not sensitive to Selumetinib (AZD-6244) in culture (PMID: 26438159). | 26438159 |
FGFR2 N549K | endometrial cancer | no benefit | Brivanib | Preclinical | Actionable | In a preclinical study, Brivanib (BMS-540215) did not inhibit growth of endometrial cancer cells harboring FGFR2 N549K in cell culture (PMID: 22238366). | 22238366 |
FGFR2 N549K | endometrial cancer | sensitive | Cediranib | Preclinical | Actionable | In a preclinical study, Cediranib (AZD-2171) inhibited growth of endometrial cancer cells harboring FGFR2 N549K in cell culture (PMID: 22238366). | 22238366 |
FGFR2 N549K | endometrial cancer | sensitive | Zoligratinib | Preclinical | Actionable | In a preclinical study, Debio 1347 inhibited proliferation of endometrial cancer cells harboring FGFR2 N549K mutation in culture (PMID: 25169980). | 25169980 |
FGFR2 N549K | Advanced Solid Tumor | resistant | Erdafitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing FGFR2 N549K were resistant to treatment with Balversa (erdafitinib) in culture and cell line xenograft models (PMID: 34272467). | 34272467 |
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 N549K in culture (PMID: 32973082). | 32973082 |
FGFR2 N549K | endometrial carcinoma | no benefit | RO5126766 | Preclinical - Cell culture | Actionable | In a preclinical study, endometrial carcinoma cells harboring FGFR2 N549K were not sensitive to RO5126766 in culture (PMID: 26438159). | 26438159 |
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 mutation in culture (PMID: 20338520). | 20338520 |
FGFR2 N549K | endometrial cancer | sensitive | Derazantinib | Preclinical - Cell culture | Actionable | In a preclinical study, Derazantinib (ARQ 087) inhibited growth of endometrial cancer cell lines harboring FGFR2 N549K in culture (PMID: 27627808). | 27627808 |
FGFR2 N549K | endometrial adenocarcinoma | sensitive | PRN1371 | Preclinical - Cell culture | Actionable | In a preclinical study, PRN1371 inhibited proliferation of endometrial adenocarcinoma cells harboring FGFR2 N549K in culture (PMID: 28978721). | 28978721 |
FGFR2 N549K | Advanced Solid Tumor | resistant | Pemigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 N549K were resistant to treatment with Pemazyre (pemigatinib) in culture (PMID: 34272467). | 34272467 |
FGFR2 N549K | Advanced Solid Tumor | conflicting | E7090 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing FGFR2 N549K did not demonstrate sensitivity to treatment with E7090 in culture, but E7090 treatment led to inhibition of tumor growth in a cell line xenograft model (PMID: 34272467). | 34272467 |
FGFR2 N549K | endometrial cancer | predicted - sensitive | Lirafugratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lirafugratinib treatment led to tumor regression in a cell line xenograft model of endometrial cancer harboring FGFR2 N549K (Cancer Res 2021;81(13_Suppl):Abstract nr 1455). | detail... |
FGFR2 N549K | endometrial cancer | predicted - sensitive | 3HP-2827 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, 3HP-2827 treatment demonstrated antitumor activity in a cell line xenograft model of endometrial cancer harboring FGFR2 N549K (Cancer Res (2024) 84 (6_Supplement): 1965). | detail... |