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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 |
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 |
---|---|---|---|---|---|
XM_006716304.2 | chr8:g.38417331G>C | c.1638C>G | p.N546K | RefSeq | GRCh38/hg38 |
XM_006716303.3 | chr8:g.38417331G>C | c.1638C>G | p.N546K | RefSeq | GRCh38/hg38 |
NM_023110.2 | chr8:g.38417331G>C | c.1638C>G | p.N546K | RefSeq | GRCh38/hg38 |
NM_023105.3 | chr8:g.38414851A>C | c.1638T>G | p.N546K | RefSeq | GRCh38/hg38 |
NM_023110 | 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_017013221.1 | 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 |
XM_017013221 | 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 |
NM_001174066.1 | 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_017013221.2 | chr8:g.38417331G>C | c.1638C>G | p.N546K | RefSeq | GRCh38/hg38 |
XM_006716310.4 | chr8:g.38414851A>C | c.1638T>G | p.N546K | RefSeq | GRCh38/hg38 |
NM_001174066.2 | 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_006716310 | chr8:g.38414851A>C | c.1638T>G | p.N546K | RefSeq | GRCh38/hg38 |
NM_001174066 | chr8:g.38414851A>C | c.1638T>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_023105 | chr8:g.38414851A>C | c.1638T>G | p.N546K | RefSeq | GRCh38/hg38 |
NM_023110.3 | chr8:g.38417331G>C | c.1638C>G | p.N546K | RefSeq | GRCh38/hg38 |
XM_006716311.1 | chr8:g.38414851A>C | c.1638T>G | p.N546K | RefSeq | GRCh38/hg38 |
XM_006716310.3 | 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_006716303.4 | 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 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR1 N546K | Advanced Solid Tumor | predicted - resistant | Fexagratinib | 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 | 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 |
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 | 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 | 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 | 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 | 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 | 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 | neuroblastoma | sensitive | Fexagratinib + 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 |