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Gene FGFR1
Variant N546K
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions FGFR1 N546K lies within the protein kinase domain of the Fgfr1 protein (UniProt.org). N546K does not confer a growth advantage in a competition assay (PMID: 34272467), but results in increased Fgfr1 protein nuclear localization, Erk, Akt, and Stat3 phosphorylation (PMID: 35488346), and kinase activity, and is transforming in cultured cells (PMID: 26179511, PMID: 23817572, PMID: 29533785).
Associated Drug Resistance
Category Variants Paths

FGFR1 mutant FGFR1 act mut FGFR1 N546K

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Transcript NM_023110.3
gDNA chr8:g.38417331G>C
cDNA c.1638C>G
Protein p.N546K
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001174066 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_006716311.1 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_017013221 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38
NM_023105 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_006716303.4 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38
XM_006716310.3 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_006716310 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_006716303.3 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38
NM_001174066.2 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_006716304.1 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38
XM_006716312.2 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
NM_023105.3 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_006716311.1 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_006716304 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38
XM_006716303 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38
XM_006716311 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_006716312 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
NM_023110.2 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38
NM_023110 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38
NM_023110.3 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38
NM_001174066.1 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_006716304.2 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38
XM_006716312.2 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_006716310.4 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_017013221.2 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38
NM_023105.2 chr8:g.38414851A>C c.1638T>G p.N546K RefSeq GRCh38/hg38
XM_017013221.1 chr8:g.38417331G>C c.1638C>G p.N546K RefSeq GRCh38/hg38

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  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR1 N546K Advanced Solid Tumor predicted - resistant AZD4547 Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with AZD4547 in culture (PMID: 34272467). 34272467
FGFR1 N546K Advanced Solid Tumor predicted - resistant Infigratinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with Truseltiq (infigratinib) in culture (PMID: 34272467). 34272467
FGFR1 N546K Advanced Solid Tumor predicted - resistant Erdafitinib Preclinical - Cell line xenograft Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with Balversa (erdafitinib) in culture, and Balversa (erdafitinib) treatment did not lead to tumor growth inhibition in a cell line xenograft model (PMID: 34272467). 34272467
FGFR1 N546K Advanced Solid Tumor predicted - resistant Futibatinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with Lytgobi (futibatinib) in culture (PMID: 34272467). 34272467
FGFR1 N546K Advanced Solid Tumor predicted - resistant Pemigatinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with Pemazyre (pemigatinib) in culture (PMID: 34272467). 34272467
FGFR1 N546K Advanced Solid Tumor predicted - resistant Dovitinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). 34272467
FGFR1 N546K pilocytic astrocytoma predicted - sensitive Pemigatinib Case Reports/Case Series Actionable In a Phase I trial (FIGHT-101), Pemazyre (pemigatinib) treatment resulted in a partial response with a 52% decrease in tumor size at first restaging and a 91% tumor reduction after 13 cycles in a patient with pilocytic astrocytoma harboring FGFR1 N546K, with the response lasting 18 months (PMID: 35507888; NCT02393248). 35507888
FGFR1 N546K neuroblastoma sensitive AZD4547 + Pictilisib Preclinical - Cell culture Actionable In a preclinical study, the combination of AZD4547 and Pictilisib (GDC-0941) resulted in greater inhibition of FGFR1 signaling, cell invasion, and colony formation compared to AZD4547 alone in neuroblastoma cell lines expressing FGFR1 N546K in culture (PMID: 35488346). 35488346
FGFR1 N546K diffuse midline glioma, H3 K27M-mutant sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Piqray (alpelisib) inhibited viability of mouse glioma cells expressing H3.3 K28M (reported as H3.3 K27M) and FGFR1 N546K (reported as N457K) in culture (PMID: 37011011). 37011011
FGFR1 N546K diffuse midline glioma, H3 K27M-mutant sensitive Infigratinib Preclinical - Cell culture Actionable In a preclinical study, Truseltiq (infigratinib) inhibited viability of mouse glioma cells expressing H3.3 K28M (reported as H3.3 K27M) and FGFR1 N546K (reported as N457K) in culture (PMID: 37011011). 37011011