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Gene | FGFR3 |
Variant | K650E |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FGFR3 K650E (also referred to as K652E from the FGFR3IIIb isoform) lies within the protein kinase domain of the Fgfr3 protein (UniProt.org). K650E confers a gain of function to the Fgfr3 protein as demonstrated by constitutive activation (PMID: 11055896), a growth advantage in a competition assay (PMID: 34272467), and transformation of cells in culture (PMID: 11157491, PMID: 34272467). |
Associated Drug Resistance | |
Category Variants Paths |
FGFR3 mutant FGFR3 act mut FGFR3 K650E |
Transcript | NM_000142.5 |
gDNA | chr4:g.1806162A>G |
cDNA | c.1948A>G |
Protein | p.K650E |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_011513422 | chr4:g.1806159A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
NM_001354809.1 | chr4:g.1806159A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
NM_000142 | chr4:g.1806162A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
XM_006713873.2 | chr4:g.1806162A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
NM_000142.4 | chr4:g.1806162A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
XM_006713873 | chr4:g.1806162A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
NM_001354809.2 | chr4:g.1806159A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
XM_006713872 | chr4:g.1806159A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
XM_006713873.1 | chr4:g.1806162A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
NM_000142.5 | chr4:g.1806162A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
XM_011513422.1 | chr4:g.1806159A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
NM_001354810.2 | chr4:g.1806159A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
XM_047449824.1 | chr4:g.1806162A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
XM_047449822.1 | chr4:g.1806159A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
XM_011513422.2 | chr4:g.1806159A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
XM_047449823.1 | chr4:g.1806162A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
NM_001354810.1 | chr4:g.1806159A>G | c.1948A>G | p.K650E | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR3 K650E | Advanced Solid Tumor | decreased response | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FGFR3 K650E demonstrated reduced sensitivity to growth inhibition by AZD4547 in culture (PMID: 26992226). | 26992226 |
FGFR3 K650E | high grade glioma | predicted - sensitive | Infigratinib | Case Reports/Case Series | Actionable | In a Phase II trial, Truseltiq (infigratinib) treatment resulted in limited efficacy with a 6-month progression-free survival (PFS) rate of 16.0%, a median PFS of 1.7 months, an objective response rate of 4.8% (1/21), and median overall survival of 6.7 months in patients with recurrent gliomas harboring alterations in FGFR1 or FGFR3, however, resulted in stable disease with PFS of 12.9 months in a patient harboring FGFR3 K650E (PMID: 35344029; NCT01975701). | 35344029 |
FGFR3 K650E | Advanced Solid Tumor | decreased response | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FGFR3 K650E demonstrated reduced sensitivity to Truseltiq (infigratinib) in culture (PMID: 28034880). | 28034880 |
FGFR3 K650E | Advanced Solid Tumor | conflicting | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 K650E were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
FGFR3 K650E | Advanced Solid Tumor | conflicting | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Dovitinib (TKI258) inhibited proliferation of transformed cells over expressing FGFR3 K650E in culture (PMID: 28034880). | 28034880 |
FGFR3 K650E | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited proliferation of transformed cells over expressing FGFR3 K650E in culture (PMID: 28034880). | 28034880 |
FGFR3 K650E | myeloid neoplasm | sensitive | Zoligratinib | Preclinical | Actionable | In a preclinical study, Debio 1347 inhibited proliferation of myeloma cell lines harboring FGFR3 K650E in culture (PMID: 25169980). | 25169980 |
FGFR3 K650E | Advanced Solid Tumor | sensitive | Zoligratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Debio 1347 inhibited proliferation of transformed cells over expressing FGFR3 K650E in culture (PMID: 28034880). | 28034880 |
FGFR3 K650E | Advanced Solid Tumor | sensitive | Erdafitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Balversa (erdafitinib) inhibited proliferation of transformed cells expressing FGFR3 K650E in culture (PMID: 26992226). | 26992226 |
FGFR3 K650E | Advanced Solid Tumor | sensitive | LY2874455 | Preclinical - Cell culture | Actionable | In a preclinical study, LY2874455 inhibited proliferation of transformed cells over expressing FGFR3 K650E in culture (PMID: 28034880). | 28034880 |
FGFR3 K650E | myeloid neoplasm | no benefit | SSR128129E | Preclinical | Actionable | In a preclinical study, SSR128129E did not inhibit proliferation of myeloma cells expressing FGFR3 K650E in culture (PMID: 23597562). | 23597562 |
FGFR3 K650E | Advanced Solid Tumor | sensitive | PD98059 | Preclinical | Actionable | In a preclinical study, PD98059 inhibited FGFR3 K650E-induced transformation of cells in culture (PMID: 14534538). | 14534538 |
FGFR3 K650E | myeloid neoplasm | sensitive | SU5402 | Preclinical - Cell culture | Actionable | In a preclinical study, SU5402 inhibited proliferation of myeloma cells expressing FGFR3 K650E in culture (PMID: 23597562). | 23597562 |
FGFR3 K650E | Advanced Solid Tumor | sensitive | FIIN-2 | Preclinical - Cell culture | Actionable | In a preclinical study, FIIN-2 inhibited proliferation of transformed cells over expressing FGFR3 K650E in culture (PMID: 28034880). | 28034880 |