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Gene | FGFR3 |
Variant | Y373C |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FGFR3 Y373C lies within the extracellular domain of the Fgfr3 protein (UniProt.org). Y373C confers a gain of function to the Fgfr3 protein resulting in increased proliferation relative to wild-type Fgfr3 in a competition assay (PMID: 34272467), constitutive activation, downstream signaling (PMID: 11429702, PMID: 11157491), and transformation of cultured cells (PMID: 11429702, PMID: 11157491, PMID: 34272467). |
Associated Drug Resistance | |
Category Variants Paths |
FGFR3 mutant FGFR3 act mut FGFR3 Y373C |
Transcript | NM_000142.5 |
gDNA | chr4:g.1804372A>G |
cDNA | c.1118A>G |
Protein | p.Y373C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_006713873.2 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_011513422.1 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_006713873.1 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_047449824.1 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_011513422 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
NM_001354809.1 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
NM_001354810.2 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_011513420.1 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_011513420.2 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_011513422.2 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_006713873 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
NM_001354809.2 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
NM_000142.5 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_011513420 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_047449823.1 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
NM_000142.4 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
NM_001354810.1 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_047449822.1 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
XM_006713872 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
NM_000142 | chr4:g.1804372A>G | c.1118A>G | p.Y373C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR3 Y373C FGFR3 over exp | multiple myeloma | sensitive | AZ8010 | Preclinical | Actionable | In a preclinical study, AZ8010 inhibited Fgfr3 signaling, induced cell-cycle arrest, and decreased proliferation of multiple myeloma cells over expressing FGFR3 Y373C in culture (PMID: 22869148). | 22869148 |
FGFR3 Y373C FGFR3 over exp | multiple myeloma | sensitive | PD173074 | Preclinical | Actionable | In a preclinical study, PD173074 inhibited Fgfr3 signaling and decreased proliferation and survival of multiple myeloma cells over expressing FGFR3 Y373C in culture (PMID: 22869148). | 22869148 |
FGFR3 rearrange FGFR3 Y373C | multiple myeloma | sensitive | Futibatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lytgobi (futibatinib) treatment led to inhibition of cell proliferation in a multiple myeloma cell line harboring an FGFR3 rearrangement and FGFR3 Y373C in culture, and led to tumor regression in a cell line xenograft model (PMID: 32973082). | 32973082 |
FGFR3 Y373C FGFR3 N540K FGFR3 V555L FGFR3 L608V | bladder urothelial carcinoma | predicted - resistant | Futibatinib | Case Reports/Case Series | Actionable | In a clinical case study, FGFR3 N540K, FGFR3 V555L, and FGFR3 L608V were identified in the post-progression circulating tumor DNA of a patient with bladder urothelial carcinoma harboring FGFR3 Y373C who previously responded to Lytgobi (futibatinib) treatment (PMID: 37377403). | 37377403 |
FGFR3 Y373C FGFR3 N540K | transitional cell carcinoma | predicted - resistant | Pemigatinib | Case Reports/Case Series | Actionable | In a Phase II trial (FIGHT-201), FGFR3 N540K was identified in post-progression biopsy in a patient with urothelial carcinoma harboring FGFR3 Y373C who previously achieved stable disease on Pemazyre (pemigatinib) treatment (PMID: 37956738; NCT02872714). | 37956738 |