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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_000142.4 |
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 |
---|---|---|---|---|---|
NM_000142 | 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_011513422 | 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_001354809.1 | 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_006713872 | 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 |
XM_011513422.1 | 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_011513420.1 | 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 | myeloid neoplasm | sensitive | Debio 1347 | Preclinical | Actionable | In a preclinical study, Debio 1347 inhibited proliferation of myeloma cell lines harboring FGFR3 Y373C in culture (PMID: 25169980). | 25169980 |
FGFR3 Y373C | myeloid neoplasm | no benefit | RO4987655 | Preclinical - Cell culture | Actionable | In a preclinical study, myeloma cells harboring FGFR3 Y373C were not sensitive to RO4987655 in culture (PMID: 26438159). | 26438159 |
FGFR3 Y373C | myeloid neoplasm | no benefit | RO5126766 | Preclinical - Cell culture | Actionable | In a preclinical study, myeloma cells harboring FGFR3 Y373C were not sensitive to RO5126766 in culture (PMID: 26438159). | 26438159 |
FGFR3 Y373C | myeloid neoplasm | no benefit | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, myeloma cells harboring FGFR3 Y373C were not sensitive to Selumetinib (AZD-6244) in culture (PMID: 26438159). | 26438159 |
FGFR3 Y373C | multiple myeloma | sensitive | E7090 | Preclinical - Cell culture | Actionable | In a preclinical study, a multiple myeloma cell line harboring FGFR3 Y373C (PMID: 19901323) demonstrated sensitivity to E7090 in culture, resulting in decreased cell viability (PMID: 27535969). | 19901323 27535969 |
FGFR3 Y373C | transitional cell carcinoma | sensitive | Erdafitinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 Y373C is included in the companion diagnostic (PMID: 31340094; NCT02365597). | detail... 31340094 detail... |
FGFR3 Y373C | bladder urothelial carcinoma | sensitive | Erdafitinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 Y373C is included in the companion diagnostic (PMID: 31340094; NCT02365597). | detail... 31340094 detail... |
FGFR3 Y373C | bladder urothelial carcinoma | predicted - sensitive | Anlotinib + Sintilimab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic bladder urothelial cancer harboring FGFR3 Y373C, PIK3CA E542K and TP53 R213* who had previously progressed on combination treatment with Sintilimab (IBI308) and Abraxane (nab-paclitaxel), achieved a partial response after 3 cycles of combination treatment with Sintilimab (IBI308) and Anlotinib (AL-3818), and stable disease has been observed for over 11 months (PMID: 34109111). | 34109111 |
FGFR3 Y373C | Advanced Solid Tumor | predicted - resistant | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 Y373C were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
FGFR3 Y373C | Advanced Solid Tumor | predicted - resistant | E7090 | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 Y373C were resistant to treatment with E7090 in culture (PMID: 34272467). | 34272467 |
FGFR3 Y373C | Advanced Solid Tumor | predicted - sensitive | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 Y373C were sensitive to treatment with Truseltiq (infigratinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |