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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

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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_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
NM_001354810.2 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_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_047449823.1 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
NM_001354809.2 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
NM_001354810.1 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
XM_047449822.1 chr4:g.1804372A>G c.1118A>G p.Y373C RefSeq GRCh38/hg38
XM_006713873.2 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
NM_000142.5 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_006713873 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 chr4:g.1804372A>G c.1118A>G p.Y373C RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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
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 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 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 myeloid neoplasm sensitive Zoligratinib Preclinical Actionable In a preclinical study, Debio 1347 inhibited proliferation of myeloma cell lines harboring FGFR3 Y373C in culture (PMID: 25169980). 25169980
FGFR3 Y373C transitional cell carcinoma sensitive Erdafitinib Guideline Actionable Balversa (erdafitinib) is included in guidelines for patients with advanced urothelial carcinoma who have received chemotherapy and an immune checkpoint inhibitor and harboring select FGFR mutations including FGFR3 Y373C (PMID: 38490358; ESMO.org). detail... 38490358
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 transitional cell carcinoma sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase III trial (THOR), Balversa (erdafitinib) treatment led to improved median overall survival (25.4 mo vs. 12.4 mo), median progression-free survival (8.4 mo vs. 2.9 mo), objective response rate (57.1% vs. 15.4%), and disease control rate (92.9% vs. 76.9%) compared to chemotherapy in Japanese patients with metastatic urothelial carcinoma with alterations in FGFR2 or FGFR3 (n=14), including FGFR3 Y373C (n=3), S249C (n=4), G370C (n=2), R248C (n=2), and FGFR3-TACC3 (n=3) (PMID: 39017806; NCT03390504). 39017806
FGFR3 Y373C bladder urothelial carcinoma sensitive Erdafitinib Guideline Actionable Balversa (erdafitinib) is included in guidelines for patients with advanced bladder urothelial carcinoma who have received chemotherapy and an immune checkpoint inhibitor and harboring select FGFR mutations including FGFR3 Y373C (PMID: 38490358; ESMO.org). 38490358 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 urinary bladder cancer sensitive Erdafitinib Phase II Actionable In a Phase II trial (THOR-2), Balversa (erdafitinib) improved median recurrence-free survival (not reached vs 11.6 mo, HR=0.28, p=0.0008) in patients with recurrent high risk non-muscle invasive bladder cancer harboring FGFR3 mutations such as S249C (n=31), R248C (n=4), G370C, (n=3) or Y373C (n=10) or FGFR2-BICC1 (n=1), FGFR3-BAIAP2L1 (n=1), or FGFR3-TACC3 (n=5) compared to intravesical chemotherapy (PMID: 37871701; NCT04172675). 37871701
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 bladder urothelial carcinoma predicted - sensitive Pemigatinib Case Reports/Case Series Actionable In a clinical case study, Pemazyre (pemigatinib) treatment resulted in a partial response with a progression-free survival of 8.4 months in a patient with bladder urothelial cancer harboring FGFR3 Y373C (PMID: 37377403). 37377403
FGFR3 Y373C urinary bladder cancer predicted - sensitive Pemigatinib Case Reports/Case Series Actionable In a Phase II trial (FIGHT-207), Pemazyre (pemigatinib) treatment resulted in a partial response with a 50.8% decrease in target lesion and a progression-free survival of 6.2 months, and stable disease with a 30% decrease in target lesion and progression-free survival of 3.9 months in two patients with bladder cancer harboring FGFR3 Y373C (Cancer Res (2023) 83 (8_Supplement): CT016; NCT03822117). detail...
FGFR3 Y373C transitional cell carcinoma predicted - sensitive Pembrolizumab + Pemigatinib Case Reports/Case Series Actionable In a Phase I trial (FIGHT-101), treatment with the combination of Pemazyre (pemigatinib) and Keytruda (pembrolizumab) demonstrated safety in patients with advanced solid tumors and resulted in an objective response rate of 26.9% (7/26, all partial responses), including a partial response with a duration of response of 4.2 months in a patient with urothelial cancer harboring FGFR3 Y373C (PMID: 38986210; NCT02393248). 38986210
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 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 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