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Gene | FGFR3 |
Variant | K650M |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FGFR3 K650M (also referred to as K652M from the FGFR3IIIb isoform) lies within the protein kinase domain of the Fgfr3 protein (UniProt.org). K650M confers a gain of function to the Fgfr3 protein as demonstrated by ligand-dependent autophosphorylation, activation of Mapk signaling (PMID: 9857065), activation of Stat1 in kinase assays (PMID: 19088846), a growth advantage in a competition assay, and increased transformation activity in cultured cells (PMID: 34272467). |
Associated Drug Resistance | |
Category Variants Paths |
FGFR3 mutant FGFR3 act mut FGFR3 K650M |
Transcript | NM_000142.5 |
gDNA | chr4:g.1806163A>T |
cDNA | c.1949A>T |
Protein | p.K650M |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_047449822.1 | chr4:g.1806160A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
XM_047449824.1 | chr4:g.1806163A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
XM_047449823.1 | chr4:g.1806163A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
XM_011513422 | chr4:g.1806160A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
NM_000142.5 | chr4:g.1806163A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
NM_000142 | chr4:g.1806163A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
XM_006713872 | chr4:g.1806160A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
XM_011513422.2 | chr4:g.1806160A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
NM_001354810.1 | chr4:g.1806160A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
XM_011513422.1 | chr4:g.1806160A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
XM_006713873.2 | chr4:g.1806163A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
XM_006713873.1 | chr4:g.1806163A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
NM_001354810.2 | chr4:g.1806160A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
NM_000142.4 | chr4:g.1806163A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
NM_001354809.2 | chr4:g.1806160A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
XM_006713873 | chr4:g.1806163A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
NM_001354809.1 | chr4:g.1806160A>T | c.1949A>T | p.K650M | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR3 K650M | Advanced Solid Tumor | sensitive | PRN1371 | Preclinical - Cell culture | Actionable | In a preclinical study, PRN1371 inhibited proliferation of transformed cells over expressing FGFR3 K650M in culture (PMID: 28978721). | 28978721 |
FGFR3 K650M | Advanced Solid Tumor | resistant | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 K650M were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
FGFR3 K650M | Advanced Solid Tumor | resistant | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 K650M were resistant to treatment with AZD4547 in culture (PMID: 34272467). | 34272467 |
FGFR3 K650M | Advanced Solid Tumor | predicted - sensitive | KIN-3248 | Preclinical - Biochemical | Actionable | In a preclinical study, KIN-3248 inhibited kinase activity of FGFR3 K650M in an in vitro assay (PMID: 38437671). | 38437671 |