FGFR3 N540K

CI-VAR-00002914Explore in graph →NP_000133.1:p.Asn540LysNM_000142.5:c.1620C>GClinVar 16338 CIViC 3693

Curated evidence

Evidence by cancer (8 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 1–8 of 8 evidence items across 3 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
Malignant Neoplasm3
FGFR3 N540K	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	accepted	EID12702 In NIH3T3 colony formation assays, cells expressing N540K displayed a transformed phenotype and showed approximately 20 fold increased colony formation over wildtype cells. In comparison, activating v… (full text at CIViC) PMID 26992226 · Patani et al., 2016 · Open in CIViC	civic
FGFR3 N540K	(oncogenic)	Oncogenic	D	Supports Oncogenicity	2	accepted	EID12881 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

ClinVar

Clinical significance (0)

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

Data not yet available

No ClinVar interpretation attached to this variant.

Urothelial Carcinoma2
FGFR3 Y373C AND FGFR3 N540K	Erdafitinib + FutibatinibSequential	Predictive	C	Supports Resistance	4	accepted	EID12704 In this study of patients with FGFR-driven urothelial carcinoma treated with selective FGFR inhibitors, longitudinal ctDNA analysis identified emergent FGFR3 kinase domain mutations at disease progres… (full text at CIViC) PMID 37377403 · Facchinetti et al., 2023 · Open in CIViC	civic
PIK3CA E545K AND FGFR3 S249C AND FGFR3 N540K	Erdafitinib	Predictive	C	Supports Resistance	4	accepted	EID12703 In this study of 21 patients with FGFR-driven urothelial carcinoma treated with selective FGFR inhibitors (including erdafitinib), post-progression molecular analyses (tissue and/or ctDNA sequencing) … (full text at CIViC) PMID 37377403 · Facchinetti et al., 2023 · Open in CIViC	civic

Unmapped disease3unmapped disease
FGFR3 N540K	(functional)	Functional	D	Supports Gain Of Function	3	accepted	EID10084 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 N540K	(functional)	Functional	D	Supports Gain Of Function	3	accepted	EID10389 FGFR3 N540K exhibited increased kinase activity compared to wild-type FGFR3, as reported in prior characterization of the mutation. In this study, FGFR3 N540K demonstrated enhanced incorporation into … (full text at CIViC) PMID 29478821 · Bunney et al., 2018 · Open in CIViC	civic
FGFR3 N540K	(functional)	Functional	D	Supports Gain Of Function	2	accepted	EID12705 Western blots were performed on Ba/F3 cells expressing driver fusion FGFR3::TACC3 and FGFR3::TACC3 plus FGFR3 N540K. In the FGFR3::TACC3 plus FGFR3 N540K cells, levels of phosphoylated FGFR (p-FGFR), … (full text at CIViC) PMID 37377403 · Facchinetti et al., 2023 · Open in CIViC	civic