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FGFR3 K650E - Gene Variant Detail

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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

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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_006713873 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
NM_000142.5 chr4:g.1806162A>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_047449823.1 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
XM_006713873.2 chr4:g.1806162A>G c.1948A>G p.K650E RefSeq GRCh38/hg38
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
XM_011513422.2 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_047449822.1 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
XM_006713872 chr4:g.1806159A>G c.1948A>G p.K650E RefSeq GRCh38/hg38
NM_001354810.1 chr4:g.1806159A>G c.1948A>G p.K650E RefSeq GRCh38/hg38
NM_001354809.2 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

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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 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 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 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 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 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
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 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