Variant · Snv

FGFR3 K650E

CI-VAR-00002157Explore in graph →NP_000133.1:p.Lys650GluNM_000142.5:c.1948A>GClinVar 16331 CIViC 1400 rs78311289

Curated evidence

Evidence by cancer (15 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–15 of 15 evidence items across 5 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Cutaneous Melanoma1
FGFR3 K650E	Vemurafenib	Predictive	D	Supports Resistance	—	submitted	EID4055 In an in vitro study, an A375 cell line expressing BRAF V600E (a known sensitizing mutation to vemurafenib) and FGFR3 K650E co-mutations, demonstrated resistance to vemurafenib treatment (IC50: 1480 n… (full text at CIViC) PMID 21107323 · Nazarian et al., 2010 · Open in CIViC	civic
Hematopoietic and Lymphoid Cell Neoplasm1
FGFR3 K650E	(oncogenic)	Oncogenic	D	Supports Oncogenicity	4	submitted	EID10370 Authors of this paper aimed to investigate the role of the FGFR3 K650E variant in transforming cells in vivo and in vitro. After 3-4 weeks of transducing mice’s bone marrow (BM) with the mutant recept… (full text at CIViC) PMID 11290605 ·

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
16331	Pathogenic	criteria provided, multiple submitters, no conflicts	2	Multiple myeloma; Spermatocytic seminoma; Thanatophoric dysplasia, type 2; Thanatophoric dysplasia type 1; FGFR3-related disorder; Thanatophoric dysplasia	germline/somatic	26	Jun 23, 2026	clinvar

Malignant Neoplasm3
FGFR3 K650E	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID12845 The tyrosine kinase domain mutation K650E was tested in a series of assays for an evaluation of oncogenicity. K650E was stably transfected into 3T3 cells along with WT controls. TAS (Transformation … (full text at CIViC) PMID 34272467 · Nakamura et al., 2021 · Open in CIViC	civic
FGFR3 K650E	(oncogenic)	Oncogenic	D	Supports Oncogenicity	2	submitted	EID12889 In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC) PMID 41361008 · Tangermann et al., 2025 · Open in CIViC	civic
FGFR3 K650E	R3Mab	Predictive	D	Does Not Support Resistance	3	accepted	EID10355 Ba/F3 cells transfected with wildtype FGFR3 resulted in IL-3 independence with FGF1 dependence for growth, whereas cells transfected with common bladder carcinoma variant FGFR3 K652E resulted in IL-3 … (full text at CIViC) PMID 19381019 · Qing et al., 2009 · Open in CIViC	civic

Malignant Neoplasm3

FGFR3 K650E

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID12845

The tyrosine kinase domain mutation K650E was tested in a series of assays for an evaluation of oncogenicity. K650E was stably transfected into 3T3 cells along with WT controls. TAS (Transformation … (full text at CIViC)

PMID 34272467 · Nakamura et al., 2021 · Open in CIViC

civic

FGFR3 K650E

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID12889

In a saturation mutagenesis study, all possible point mutations in the FGFR 1-4 kinase domain (amino acids 472-807 for FGFR3) were tested. Lentiviral plasmids were infected at MOI < 0.3 into the growt… (full text at CIViC)

PMID 41361008 · Tangermann et al., 2025 · Open in CIViC

civic

FGFR3 K650E

R3Mab

Predictive

Does Not Support Resistance

accepted

EID10355

Ba/F3 cells transfected with wildtype FGFR3 resulted in IL-3 independence with FGF1 dependence for growth, whereas cells transfected with common bladder carcinoma variant FGFR3 K652E resulted in IL-3 … (full text at CIViC)

PMID 19381019 · Qing et al., 2009 · Open in CIViC

civic

Multiple Myeloma3
FGFR3 K650E	(oncogenic)	Oncogenic	D	Supports Oncogenicity	1	submitted	EID10383 Xenografts of multiple myeloma cell line OPM2 (FGFR3 K650E) into nude mice resulted in tumor growth. PMID 19381019 · Qing et al., 2009 · Open in CIViC	civic
FGFR3 K650E	Midostaurin	Predictive	D	Supports Sensitivity Response	3	submitted	EID10407 PKC412 inhibited the growth of FGFR3 K650E-transformed Ba/F3 cells. Researchers introduced an N540D mutation to FGFR3-transformed Ba/F3 cells, which reduces inhibition of the FGFR3 K650E-transformed c… (full text at CIViC) PMID 16091734 · Chen et al., 2005 · Open in CIViC	civic
FGFR3 K650E	R3Mab	Predictive	D	Supports Sensitivity Response	4	submitted	EID10365 In culture, monoclonal antibody R3Mab treatment inhibited the growth of multiple myeloma cell line UTMC-2 which has wild type FGFR3 but did not affect proliferation of multiple myeloma cell line KMS11… (full text at CIViC) PMID 19381019 · Qing et al., 2009 · Open in CIViC	civic

Multiple Myeloma3

FGFR3 K650E

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID10383

Xenografts of multiple myeloma cell line OPM2 (FGFR3 K650E) into nude mice resulted in tumor growth.

PMID 19381019 · Qing et al., 2009 · Open in CIViC

civic

FGFR3 K650E

Midostaurin

Predictive

Supports Sensitivity Response

submitted

EID10407

PKC412 inhibited the growth of FGFR3 K650E-transformed Ba/F3 cells. Researchers introduced an N540D mutation to FGFR3-transformed Ba/F3 cells, which reduces inhibition of the FGFR3 K650E-transformed c… (full text at CIViC)

PMID 16091734 · Chen et al., 2005 · Open in CIViC

civic

FGFR3 K650E

R3Mab

Predictive

Supports Sensitivity Response

submitted

EID10365

In culture, monoclonal antibody R3Mab treatment inhibited the growth of multiple myeloma cell line UTMC-2 which has wild type FGFR3 but did not affect proliferation of multiple myeloma cell line KMS11… (full text at CIViC)

PMID 19381019 · Qing et al., 2009 · Open in CIViC

civic

Unmapped disease7unmapped disease
FGFR3 K650E	(functional)	Functional	D	Supports Gain Of Function	3	submitted	EID10086 25 FGFR3 mutant proteins were isolated and their auto-phosphorylation and kinase activity was measured and compared to wild-type. 6 mutations (N540K, N540S, K650E, K650N, R669G, R669Q) demonstrated in… (full text at CIViC) PMID 26992226 · Patani et al., 2016 · Open in CIViC	civic
FGFR3 K650E	(functional)	Functional	D	Supports Gain Of Function	1	submitted	EID10376 The Lys650Glu variant was investigated in terms of its ability to activate the receptor kinase FGFR3. Upon NIH3T3 cells transfection, the kinase assay showed a significant increase in the ligand-indep… (full text at CIViC) PMID 10053006 · Tavormina et al., 1999 · Open in CIViC	civic
FGFR3 K650E	(functional)	Functional	D	Supports Gain Of Function	1	accepted	EID10381 The FGFR3 variant K650E is known to be responsible for thanatophoric dysplasia type 2 (TDII), a severe form of skeletal dysplasia. The mutant receptor was tested for comparison between other variants … (full text at CIViC) PMID 11055896 · Bellus et al., 2000 · Open in CIViC	civic
FGFR3 K650E	(functional)	Functional	D	Supports Unaltered Function	2	submitted	EID10391 Protein co-chaperone Cdc37 is required in FGFR3 remodeling for recognition by chaperone protein Hsp90. Cdc37 must partially deactivate the kinase and present it in a particular orientation to Hsp90. A… (full text at CIViC) PMID 29478821 · Bunney et al., 2018 · Open in CIViC	civic
FGFR3 K650E	(functional)	Functional	D	Supports Gain Of Function	3	accepted	EID10393 NIH 3T3 cells were transfected with wild-type and mutant K650E FGFR3. Immunoprecipitation measuring kinase activity showed FGFR3 K650E had 100-fold greater autophosphorylation than wildtype. The autho… (full text at CIViC) PMID 8754806 · Webster et al., 1996 · Open in CIViC	civic
FGFR3 K650E	(functional)	Functional	D	Supports Gain Of Function	3	accepted	EID10493 A construct of PDGF and FGFR3 was created as a chimeric receptor to study the effect of the K650E variant on downstream signaling pathways. Transfecting PC12 cells showed continuous ligand-independent… (full text at CIViC) PMID 15843401 · Nowroozi et al., 2005 · Open in CIViC	civic
FGFR3 K650E	(functional)	Functional	D	Supports Gain Of Function	3	submitted	EID10653 Rare germline and somatic cancer variant FGFR3 K650E crystal structure was compared to phosphorylated and unphosphorylated FGF1 and FGF2 via superimposition. This comparison showed that K650E (located… (full text at CIViC) PMID 23972473 · Huang et al., 2013 · Open in CIViC	civic

Unmapped disease7unmapped disease

FGFR3 K650E

(functional)

Functional

Supports Gain Of Function

submitted

EID10086

25 FGFR3 mutant proteins were isolated and their auto-phosphorylation and kinase activity was measured and compared to wild-type. 6 mutations (N540K, N540S, K650E, K650N, R669G, R669Q) demonstrated in… (full text at CIViC)

PMID 26992226 · Patani et al., 2016 · Open in CIViC

civic

FGFR3 K650E

(functional)

Functional

Supports Gain Of Function

submitted

EID10376

The Lys650Glu variant was investigated in terms of its ability to activate the receptor kinase FGFR3. Upon NIH3T3 cells transfection, the kinase assay showed a significant increase in the ligand-indep… (full text at CIViC)

PMID 10053006 · Tavormina et al., 1999 · Open in CIViC

civic

FGFR3 K650E

(functional)

Functional

Supports Gain Of Function

accepted

EID10381

The FGFR3 variant K650E is known to be responsible for thanatophoric dysplasia type 2 (TDII), a severe form of skeletal dysplasia. The mutant receptor was tested for comparison between other variants … (full text at CIViC)

PMID 11055896 · Bellus et al., 2000 · Open in CIViC

civic

FGFR3 K650E

(functional)

Functional

Supports Unaltered Function

submitted

EID10391

Protein co-chaperone Cdc37 is required in FGFR3 remodeling for recognition by chaperone protein Hsp90. Cdc37 must partially deactivate the kinase and present it in a particular orientation to Hsp90. A… (full text at CIViC)

PMID 29478821 · Bunney et al., 2018 · Open in CIViC

civic

FGFR3 K650E

(functional)

Functional

Supports Gain Of Function

accepted

EID10393

NIH 3T3 cells were transfected with wild-type and mutant K650E FGFR3. Immunoprecipitation measuring kinase activity showed FGFR3 K650E had 100-fold greater autophosphorylation than wildtype. The autho… (full text at CIViC)

PMID 8754806 · Webster et al., 1996 · Open in CIViC

civic

FGFR3 K650E

(functional)

Functional

Supports Gain Of Function

accepted

EID10493

A construct of PDGF and FGFR3 was created as a chimeric receptor to study the effect of the K650E variant on downstream signaling pathways. Transfecting PC12 cells showed continuous ligand-independent… (full text at CIViC)

PMID 15843401 · Nowroozi et al., 2005 · Open in CIViC

civic

FGFR3 K650E

(functional)

Functional

Supports Gain Of Function

submitted

EID10653

Rare germline and somatic cancer variant FGFR3 K650E crystal structure was compared to phosphorylated and unphosphorylated FGF1 and FGF2 via superimposition. This comparison showed that K650E (located… (full text at CIViC)

PMID 23972473 · Huang et al., 2013 · Open in CIViC

civic