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 oncogenic transformation in cell-based studies (PMID: 18552176, PMID: 17803937, PMID: 29533785) and increased MAPK pathway signaling in cultured cells (PMID: 19147536).
Associated Drug Resistance Y

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Transcript NM_000141
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 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_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

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 cancer sensitive Debio 1347 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 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 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 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 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-01 inhibited proliferation of endometrial carcinoma cell lines harboring FGFR2 N549K mutation in culture (PMID: 20338520). 20338520
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 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 sensitive Debio 1347 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 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 sensitive FIIN-1 Preclinical Actionable In a preclinical study, FIIN-01 inhibited proliferation of endometrial carcinoma cell lines harboring FGFR2 N549K and FGFR2 K310R mutations in culture (PMID: 20338520). 20338520
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 - ZMYM4 FGFR2 N549H FGFR2 N549K FGFR2 V564F FGFR2 E565A FGFR2 K659M cholangiocarcinoma predicted - resistant Infigratinib Case Reports/Case Series Actionable In a clinical case study, FGFR2 mutations E565A, K659M, N549H, N549K and V564F were identified in the cell-free DNA of a cholangiocarcinoma patient harboring FGFR2-ZMYM4 fusion after the patient progressed while on Infigratinib (BGJ398) treatment (PMID: 28034880). 28034880
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 act mut Advanced Solid Tumor predicted - sensitive Erdafitinib Phase I Actionable In a Phase I trial, Balversa (erdafitinib) treatment resulted in stable disease in 70% (16/23) and partial response in 22% (5/23) of patients with advanced solid tumors harboring FGFR 1-4 activating mutations (including amplifications, mutations and translocations), while no antitumor activity was observed in patients with unknown or no known changes in FGFR (PMID: 26324363; NCT01703481). 26324363
FGFR2 act mut Advanced Solid Tumor decreased response Cediranib Preclinical Actionable In a preclinical study, transformed cells expressing constitutively active FGFR2 demonstrated reduced sensitivity to inhibition of receptor phosphorylation and cell proliferation by Cediranib (AZD-2171) in culture, when compared to other tyrosine kinase inhibitors (PMID: 22238366). 22238366
FGFR2 act mut Advanced Solid Tumor sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 (CH5183284) dosing regimen has been determined in solid tumor patients with activating FGFR2 alterations (JCO, Vol 33, No 15_suppl (May 20 Supplement), 2015: 2540). detail...
FGFR2 act mut Advanced Solid Tumor predicted - sensitive AZD4547 Phase II Actionable In a Phase II (MATCH) trial, AZD4547 treatment resulted in an overall response rate of 10.5% (2/19) in patients with advanced solid tumors harboring FGFR2 or 3 activating single nucleotide variants and a 6-month progression-free survival rate of 6%, with a partial response in 1 and stable disease in 2 of 12 patients with FGFR2 activating mutations (PMID: 32463741; NCT02465060). 32463741
FGFR2 act mut endometrial cancer sensitive Dovitinib Preclinical - Cell line xenograft Actionable In a preclinical study, both cell lines and cell line xenograft models of endometrial cancer with FGFR2 activating mutations showed greater sensitivity to Dovitinib (TKI258) as compared to FGFR2 wild-type (PMID: 23443805). 23443805
FGFR2 act mut Advanced Solid Tumor sensitive Dovitinib Preclinical Actionable In a preclinical study, Dovitinib (TKI258) inhibited receptor phosphorylation and cell proliferation in transformed cells expressing constitutively active FGFR2 in culture (PMID: 22238366). 22238366
FGFR2 act mut Advanced Solid Tumor decreased response Brivanib Preclinical Actionable In a preclinical study, transformed cells expressing constitutively active FGFR2 demonstrated reduced sensitivity to inhibition of receptor phosphorylation and cell proliferation by Brivanib (BMS-540215) in culture, when compared to other tyrosine kinase inhibitors (PMID: 22238366). 22238366
FGFR2 act mut Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited receptor phosphorylation and cell growth in transformed cells expressing constitutively active FGFR2 in culture (PMID: 22238366). 22238366
FGFR2 act mut Advanced Solid Tumor decreased response Nintedanib Preclinical Actionable In a preclinical study, transformed cells expressing constitutively active FGFR2 demonstrated reduced sensitivity to Ofev (Nintedanib) in culture, when compared to other tyrosine kinase inhibitors (PMID: 22238366). 22238366
FGFR2 act mut stomach carcinoma sensitive S-49076 Preclinical - Cell line xenograft Actionable In a preclinical study, S-49076 inhibited Met activation, resulting in growth inhibition of gastric carcinoma cells harboring FGFR2 activating mutations in culture and in cell line xenograft models (PMID: 23804704). 23804704
FGFR2 mutant endometrial cancer sensitive Infigratinib Preclinical Actionable In a preclinical study, Infigratinib (BGJ398) inhibited the growth of FGFR2-mutated endometrial cancer cells in vitro and in xenograft models (PMID: 23443805). 23443805
FGFR2 mutant transitional cell carcinoma sensitive Erdafitinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597). detail... 31340094 detail...
FGFR2 mutant transitional cell carcinoma sensitive Erdafitinib Guideline Actionable Balversa (erdafitinib) is included in the guidelines for patients with advanced or metastatic urothelial carcinoma harboring Fgfr2 alterations after progression on platinum-based regimens (NCCN.org). detail...
FGFR2 mutant Advanced Solid Tumor sensitive Pemigatinib Preclinical - Cell culture Actionable In a preclinical study, a variety of cancer cell lines harboring mutations in FGFR1, FGFR2, and/or FGFR3 demonstrated sensitivity to Pemazyre (pemigatinib) in culture and in cell line xenograft models, resulting in inhibition of tumor growth (Cancer Res 2015;75(15 Suppl):Abstract nr 771). detail...
FGFR2 mutant cholangiocarcinoma sensitive Infigratinib Case Reports/Case Series Actionable In a Phase I trial, a patient with cholangiocarcinoma harboring an FGFR2 mutation demonstrated a decreased tumor burden when treated with Infigratinib (BGJ398) (PMID: 27870574). 27870574
FGFR2 mutant bladder urothelial carcinoma sensitive Erdafitinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597). detail... 31340094 detail...
FGFR2 mutant bladder urothelial carcinoma sensitive Erdafitinib Guideline Actionable Balversa (erdafitinib) is included in the guidelines for patients with advanced or metastatic urothelial carcinoma harboring Fgfr2 alterations after progression on platinum-based regimens (NCCN.org). detail...
FGFR2 mutant cholangiocarcinoma predicted - sensitive Erdafitinib Phase I Actionable In a Phase I trial, Balversa (erdafitinib) treatment resulted in an objective response rate of 27% (3/11) in patients with cholangiocarcinoma harboring FGFR genomic alterations, including 1 with FGFR2 mutation, 2 with FGFR3 mutations, and 8 with FGFR2 fusions (PMID: 31088831; NCT01703481). 31088831
FGFR2 mutant endometrial cancer sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of endometrial cancer cells harboring FGFR2 mutations in culture (AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1249). detail...
FGFR2 mutant Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300