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| Gene | FGFR3 |
| Variant | V555M |
| Impact List | missense |
| Protein Effect | gain of function |
| Gene Variant Descriptions | FGFR3 V555M lies within the protein kinase domain of the Fgfr3 protein (UniProt.org). V555M results in increased Fgfr3 autophosphorylation and substrate phosphorylation in cell culture (PMID: 26992226), and is associated with resistance to Fgfr inhibitors in culture (PMID: 28034880). |
| Associated Drug Resistance | Y |
| Category Variants Paths |
FGFR3 mutant FGFR3 act mut FGFR3 V555M |
| Transcript | NM_000142.5 |
| gDNA | chr4:g.1805767G>A |
| cDNA | c.1663G>A |
| Protein | p.V555M |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_000142.4 | chr4:g.1805767G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| XM_006713873.2 | chr4:g.1805767G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| XM_006713871.1 | chr4:g.1805761G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| NM_001163213.2 | chr4:g.1805761G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| XM_006713871 | chr4:g.1805761G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| XM_011513420.2 | chr4:g.1805761G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| XM_006713873 | chr4:g.1805767G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| NM_000142 | chr4:g.1805767G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| XM_006713871.2 | chr4:g.1805761G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| NM_001163213.1 | chr4:g.1805761G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| XM_047449823.1 | chr4:g.1805767G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| NM_001163213 | chr4:g.1805761G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| XM_011513420.1 | chr4:g.1805761G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| XM_011513420 | chr4:g.1805761G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| NM_000142.5 | chr4:g.1805767G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| XM_006713873.1 | chr4:g.1805767G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| XM_047449824.1 | chr4:g.1805767G>A | c.1663G>A | p.V555M | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| FGFR3 V555M | Advanced Solid Tumor | resistant | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FGFR3 V555M were resistant to Truseltiq (infigratinib) in culture (PMID: 28034880). | 28034880 |
| FGFR3 V555M | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited proliferation of transformed cells over expressing FGFR3 V555M in culture (PMID: 28034880). | 28034880 |
| FGFR3 V555M | Advanced Solid Tumor | sensitive | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Dovitinib (TKI258) inhibited proliferation of transformed cells over expressing FGFR3 V555M in culture (PMID: 28034880). | 28034880 |
| FGFR3 V555M | Advanced Solid Tumor | resistant | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FGFR3 V555M were resistant to Fexagratinib (AZD4547) in culture (PMID: 28034880). | 28034880 |
| FGFR3 V555M | Advanced Solid Tumor | decreased response | Zoligratinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FGFR3 V555M demonstrated reduced sensitivity to Debio 1347 in culture (PMID: 28034880). | 28034880 |
| FGFR3 V555M | Advanced Solid Tumor | decreased response | FIIN-2 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FGFR3 V555M demonstrated reduced sensitivity to FIIN-2 in culture (PMID: 28034880). | 28034880 |
| FGFR3 V555M | Advanced Solid Tumor | sensitive | LY2874455 | Preclinical - Cell culture | Actionable | In a preclinical study, LY2874455 inhibited proliferation of transformed cells over expressing FGFR3 V555M in culture (PMID: 28034880). | 28034880 |
| FGFR3 V555M | transitional cell carcinoma | resistant | Infigratinib | Case Reports/Case Series | Actionable | In a clinical study, a patient with metastatic urothelial carcinoma progressed while being treated with Truseltiq (infigratinib) and subsequent cell-free DNA testing revealed FGFR3 V555M (also corresponds to V443M) (PMID: 29848605). | 29848605 |
| FGFR3 V555M | Advanced Solid Tumor | resistant | Pemigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a cell line expressing FGFR3 V555M was resistant to Pemazyre (pemigatinib) in a kinase assay and in culture (PMID: 36698015). | 36698015 |