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Gene | FGFR3 |
Variant | K652E |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | FGFR3 K652E (corresponds to K650E in the canonical isoform) lies within the protein kinase domain of the Fgfr3 protein (UniProt.org). K652E results in constitutive phosphorylation of Src, Akt and Erk phosphorylation similar to wild-type Fgfr3, and anchorage-independent growth in cultured cells (PMID: 32370101), and has been demonstrated to induce transformation of mouse fibroblasts, but has a lesser degree of signaling and phenotypic effect in immortalized normal human urothelial cells (PMID: 19749790), and therefore, is predicted to lead to a gain of Fgfr3 protein function. |
Associated Drug Resistance | Y |
Category Variants Paths |
FGFR3 mutant FGFR3 act mut FGFR3 K652E |
Transcript | NM_001163213.2 |
gDNA | chr4:g.1806162A>G |
cDNA | c.1954A>G |
Protein | p.K652E |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_006713870 | chr4:g.1806159A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
XM_006713871 | chr4:g.1806162A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
XM_011513420.2 | chr4:g.1806162A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
NM_001163213.2 | chr4:g.1806162A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
NM_001163213 | chr4:g.1806162A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
XM_006713871.2 | chr4:g.1806162A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
XM_006713871.1 | chr4:g.1806162A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
XM_006713870.2 | chr4:g.1806159A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
XM_011513420 | chr4:g.1806162A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
XM_006713870.1 | chr4:g.1806159A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
XM_011513420.1 | chr4:g.1806162A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
XM_047449821.1 | chr4:g.1806159A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
NM_001163213.1 | chr4:g.1806162A>G | c.1954A>G | p.K652E | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR3 K652E | Advanced Solid Tumor | sensitive | Vofatamab | Preclinical - Cell culture | Actionable | In a preclinical study, Vofatamab (B-701) inhibited ligand-dependent cell proliferation in cells expressing FGFR3 K652E in culture (PMID: 19381019). | 19381019 |
FGFR3 K652E | urinary bladder cancer | sensitive | Derazantinib | Preclinical - Cell culture | Actionable | In a preclinical study, Derazantinib (ARQ 087) inhibited growth of bladder cancer cells harboring FGFR3 K652E in culture (PMID: 27627808). | 27627808 |
FGFR3 K652E | urinary bladder cancer | resistant | PD173074 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, bladder cancer cells harboring FGFR3 K652E were resistant to PD173074 in culture and in cell line xenograft models (PMID: 23558953). | 23558953 |
FGFR3 K652E | Advanced Solid Tumor | sensitive | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) decreased viability of a cell line expressing FGFR3 K652E in culture (PMID: 32370101). | 32370101 |
FGFR3 K652E | Advanced Solid Tumor | sensitive | Dasatinib + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Truseltiq (infigratinib) and Sprycel (dasatinib) treatment inhibited viability of a cell line expressing FGFR3 K652E in culture (PMID: 32370101). | 32370101 |