[Paper-level Aggregated] PMCID: PMC2789045

Evidence Type(s): Functional

Summary: Mutation: S249C | Summary: The S249C mutation in FGFR3 alters molecular function by inducing phosphorylation of FRS2alpha and ERK1/2, leading to increased proliferation, viability, and cell cycle alterations in urothelial cells. It is associated with ligand-independent dimerization, strong constitutive phosphorylation, and increased phosphorylation of PLCgamma1, indicating a significant change in molecular function.

Evidence Type: Functional Mutation: Y375C | Summary: The Y375C mutation in FGFR3 alters molecular function by inducing phosphorylation of FRS2alpha and ERK1/2, resulting in increased proliferation, viability, and changes in cell morphology. It exhibits an intermediate cell cycle profile and shows increased phosphorylation of PLCgamma1, indicating a functional impact on cell cycle-related proteins and signaling pathways.

Evidence Type: Functional Mutation: K652E | Summary: The K652E mutation in FGFR3 alters molecular function by resulting in high levels of constitutive receptor phosphorylation and activating downstream signaling pathways. It is associated with changes in cell morphology and behavior, but does not induce the same proliferative effects as S249C and Y375C. The mutation shows a lack of constitutive PLCgamma1 phosphorylation and reduced viability and saturation density in TERT-NHUC cells, indicating a distinct functional impact compared to other mutants.

Gene→Variant (gene-first): FGFR3(2261):S249C FGFR3(2261):Y375C FGFR3(2261):K652E

Genes: FGFR3(2261)

Variants: S249C Y375C K652E

[Paper-level Aggregated] PMCID: PMC2789045

Evidence Type(s): Oncogenic

Summary: Mutation: K652E | Summary: The K652E mutation in FGFR3 contributes to tumor development or progression, as suggested by its impact on cell viability in the context of mutant FGFR3 expression.

Evidence Type: Oncogenic Mutation: S249C | Summary: The S249C mutation in FGFR3 is linked to morphological transformation, increased proliferation, and colony formation in soft agar, indicating its role in tumor development.

Evidence Type: Oncogenic Mutation: Y762F | Summary: The Y762F mutation, when combined with S249C, contributes to morphological transformation and increased proliferation in NIH-3T3 cells, supporting its oncogenic potential.

Gene→Variant (gene-first): FGFR3(2261):K652E FGFR3(2261):S249C FGFR3(2261):Y762F

Genes: FGFR3(2261)

Variants: K652E S249C Y762F

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 23

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation in FGFR3 is associated with altered cell cycle distribution and viability, indicating a change in molecular function related to PLCgamma1 signaling. Evidence Type: Functional | Mutation: Y762F | Summary: The Y762F mutation, when combined with S249C, shows an increase in cell numbers at confluence, suggesting it also alters molecular function in the context of FGFR3 signaling. Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation is linked to reduced viability and saturation density in TERT-NHUC cells, indicating a functional impact on cell behavior.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y762F

Genes: 2261

Variants: K652E S249C Y762F

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 22

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation is associated with a lack of constitutive PLCgamma1 phosphorylation, suggesting it alters molecular function related to PLCgamma1 signaling. Evidence Type: Oncogenic | Mutation: S249C | Summary: The S249C mutation in FGFR3 is linked to morphological transformation, increased proliferation, and colony formation in soft agar, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: Y762F | Summary: The Y762F mutation, when combined with S249C, contributes to morphological transformation and increased proliferation in NIH-3T3 cells, supporting its oncogenic potential.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y762F

Genes: 2261

Variants: K652E S249C Y762F

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation exhibits complete ligand-independence, failing to stimulate signaling in response to FGF1 treatment. Evidence Type: Functional | Mutation: Y375C | Summary: The Y375C mutation shows a small increase in ERK1/2 activation in response to FGF1 treatment, indicating altered molecular function. Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation displays increased phosphorylation of PLCgamma1, ERK1/2, and FRS2alpha in response to FGF1 treatment, suggesting a significant alteration in molecular function.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 19

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation in FGFR3 exhibits strong constitutive phosphorylation, indicating a change in molecular function that leads to ligand-independence. Evidence Type: Functional | Mutation: Y375C | Summary: The Y375C mutation in FGFR3 shows increased levels of phosphorylation in response to ligand stimulation, suggesting an alteration in molecular function. Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation in FGFR3 also demonstrates increased phosphorylation levels in response to ligand stimulation, indicating a change in molecular function.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation in FGFR3 was associated with increased phosphorylation of PLCgamma1, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: Y375C | Summary: The Y375C mutation in FGFR3 was linked to increased phosphorylation of PLCgamma1, suggesting a change in biochemical function.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation in FGFR3 alters the phosphorylation levels and activation state of the receptor, indicating a change in molecular function. Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation in FGFR3 leads to ligand-independent dimerization, suggesting an alteration in molecular function. Evidence Type: Functional | Mutation: Y375C | Summary: The Y375C mutation in FGFR3 also results in ligand-independent dimerization, indicating a change in molecular function.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation in FGFR3 is associated with altered molecular function, as indicated by the differential expression of regulators of cell survival affecting cell viability. Evidence Type: Oncogenic | Mutation: K652E | Summary: The K652E mutation in FGFR3 contributes to tumor development or progression, as suggested by its impact on cell viability in the context of mutant FGFR3 expression.

Gene→Variant (gene-first): 2261:K652E

Genes: 2261

Variants: K652E

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation in FGFR3 alters the expression and phosphorylation of the retinoblastoma protein (RB) and increases CDK1 levels, indicating a change in molecular function related to cell cycle regulation. Evidence Type: Functional | Mutation: Y375C | Summary: The Y375C mutation in FGFR3 is associated with altered expression and phosphorylation of the retinoblastoma protein (RB) and increased CDK1 levels, suggesting a functional impact on cell cycle-related proteins. Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation in FGFR3 results in a distinct protein profile with low RB and intermediate CDK1 levels, indicating a change in molecular function compared to other mutants.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation in FGFR3 is associated with increased cell viability at confluence compared to controls, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: Y375C | Summary: The Y375C mutation in FGFR3 also shows increased cell viability at confluence, suggesting it alters molecular or biochemical function.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation alters the cell cycle profile, with a lower percentage of cells in the G0/G1 phase compared to control cells, indicating a change in molecular function. Evidence Type: Functional | Mutation: Y375C | Summary: The Y375C mutation exhibits a cell cycle profile that is intermediate between S249C mutants and control cells, suggesting an alteration in molecular function. Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation shows a cell cycle profile that is also intermediate between S249C mutants and control cells, indicating a change in molecular function.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation in FGFR3 does not significantly alter the saturation density of cells compared to controls, indicating a lack of a strong phenotypic effect. Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation shows a greater phenotypic effect compared to K652E and wildtype FGFR3, suggesting it alters molecular or biochemical function. Evidence Type: Functional | Mutation: Y375C | Summary: The Y375C mutation is associated with a phenotypic effect that is less than S249C but greater than K652E, indicating it also alters molecular or biochemical function.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation in FGFR3 alters the molecular behavior of urothelial cells, leading to increased saturation density and changes in cell morphology. Evidence Type: Functional | Mutation: Y375C | Summary: The Y375C mutation in FGFR3 results in increased saturation density and morphological changes in urothelial cells, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation in FGFR3 is associated with changes in cell morphology and behavior, suggesting an alteration in molecular function, although specific effects were not detailed in the passage.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation alters molecular function by resulting in high levels of constitutive receptor phosphorylation and activating downstream signaling pathways. Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation alters molecular function by leading to receptor activation and increased phosphorylation of downstream signaling proteins. Evidence Type: Functional | Mutation: Y375C | Summary: The Y375C mutation alters molecular function by causing receptor activation and increased phosphorylation of downstream signaling proteins.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S249C | Summary: The S249C mutation alters molecular function by inducing phosphorylation of FRS2alpha and ERK1/2, and is associated with increased proliferation and viability in urothelial cells. Evidence Type: Functional | Mutation: Y375C | Summary: The Y375C mutation alters molecular function by inducing phosphorylation of FRS2alpha and ERK1/2, and is associated with increased proliferation and viability in urothelial cells. Evidence Type: Functional | Mutation: K652E | Summary: The K652E mutation does not induce phosphorylation of PLCgamma1 and fails to promote the same proliferative effects seen with S249C and Y375C, indicating a distinct functional impact.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paper-level Aggregated] PMCID: PMC2789045

Evidence Type(s): Oncogenic, Functional, Predictive

Justification: Oncogenic: The evidence indicates that mutations S249C, Y375C, and K652E in FGFR3 lead to increased cell proliferation, morphological transformation, and anchorage-independent growth, suggesting that these mutations contribute to oncogenic processes in bladder tumors. Functional: The study demonstrates that the FGFR3 mutations affect signaling pathways and cellular behaviors, such as phosphorylation of downstream effectors and changes in cell cycle profiles, indicating a functional impact of these mutations on urothelial cells. Predictive: The differential effects of the FGFR3 mutations on cell proliferation and viability suggest that the presence of specific mutations like S249C and Y375C may predict the behavior of bladder cancer cells in response to growth conditions and treatments.

Gene→Variant (gene-first): FGFR3(2261):K652E FGFR3(2261):S249C FGFR3(2261):Y375C FGFR3(2261):Y762F

Genes: FGFR3(2261)

Variants: K652E S249C Y375C Y762F

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 23

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the S249C and K652E mutations affect cell viability and signaling pathways, indicating that these variants alter molecular or biochemical functions related to cell growth and density. Oncogenic: The evidence suggests that the S249C and K652E mutations contribute to tumor development or progression by affecting cell cycle phases and viability, which are indicative of cancer-driving behavior.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y762F

Genes: 2261

Variants: K652E S249C Y762F

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 22

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the S249C+Y762F FGFR3 mutant protein's ability to induce morphological transformation and increased proliferation in NIH-3T3 cells, indicating its role in tumor development or progression. Functional: The passage describes how the S249C+Y762F mutation affects the phosphorylation of PLCgamma1 and alters the activation of downstream signaling pathways, demonstrating a change in molecular function.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y762F

Genes: 2261

Variants: K652E S249C Y762F

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the K652E, S249C, and Y375C mutations alter the signaling response to FGF1 treatment, indicating that these variants affect molecular function related to phosphorylation and activation of signaling pathways. Oncogenic: The context of the mutations being discussed in relation to their effects on signaling pathways suggests that they may contribute to tumor development or progression, particularly given the focus on their responses in cancer-related cellular contexts.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the response of cells expressing mutant FGFR3 variants (S249C, Y375C, K652E) to FGF1 stimulation, indicating a correlation with receptor activation and signaling, which relates to treatment response. Functional: The passage describes how the variants S249C, Y375C, and K652E affect the phosphorylation of FGFR3, indicating that these mutations alter the molecular function of the receptor in response to ligand stimulation.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the increased phosphorylation of PLCgamma1 specifically in cells expressing the S249C and Y375C FGFR3 variants, indicating that these variants alter molecular function. Oncogenic: The mention of increased phosphorylation of signaling proteins in cells expressing the FGFR3 mutants suggests that these variants contribute to tumor development or progression.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the K652E, S249C, and Y375C variants of FGFR3 alter phosphorylation levels and dimerization behavior, indicating changes in molecular function. Oncogenic: The variants are described in the context of their constitutive activation and behavior in urothelial cells, suggesting their role in tumor development or progression.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the expression of proteins involved in cell survival and suggests that the K652E variant may alter the viability of cells, indicating a change in molecular function. Oncogenic: The context implies that the K652E variant contributes to tumor behavior by affecting cell viability, which is a characteristic of oncogenic variants.

Gene→Variant (gene-first): 2261:K652E

Genes: 2261

Variants: K652E

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants S249C, Y375C, and K652E FGFR3 alter the expression and phosphorylation of cell cycle-related proteins, indicating a change in molecular function.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the viability of cells expressing specific variants (S249C and Y375C) compared to controls, indicating that these variants alter the molecular or biochemical function of FGFR3, affecting cell viability. Oncogenic: The evidence suggests that the variants S249C and Y375C contribute to tumor development or progression by enhancing cell viability, which is a characteristic of oncogenic behavior.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Justification: Functional: The mention of K652E and Y375C variants also suggests alterations in cell cycle profiles, indicating a change in molecular function related to cell cycle dynamics.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 6

Evidence Type(s): Diagnostic, Functional

Justification: Diagnostic: The passage discusses the relative frequencies of the mutations K652E, S249C, and Y375C in bladder tumors, indicating an association with the disease. Functional: The passage mentions the phenotypic effects of the variants, suggesting that they alter the behavior of cells expressing these mutations compared to controls.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the expression of mutant FGFR3 variants S249C and Y375C alters the saturation density and morphology of normal urothelial cells, indicating a change in molecular or biochemical function. Oncogenic: The expression of the mutant FGFR3 variants is associated with changes in cell behavior, such as increased saturation density and altered morphology, which suggests a contribution to tumor development or progression.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the ability of the FGFR3 mutations (S249C, Y375C, and K652E) to transform NIH-3T3 cells, indicating that these somatic variants contribute to tumor development or progression. Functional: The passage describes how the FGFR3 mutations alter molecular function, specifically through increased phosphorylation of various proteins and changes in cell morphology and proliferation, demonstrating their biochemical activity.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the FGFR3 mutations (S249C, Y375C, and K652E) alter molecular signaling pathways, specifically the phosphorylation of various proteins, indicating a change in biochemical function. Oncogenic: The passage describes how the mutant FGFR3 variants induce morphological transformation, cell proliferation, and anchorage-independent growth, which are indicative of their role in tumor development and progression.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 23

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the S249C and K652E mutations affect cell viability and signaling pathways, indicating that these variants alter molecular or biochemical functions related to cell growth and density. Oncogenic: The evidence suggests that the S249C and K652E mutations contribute to tumor development or progression by affecting cell cycle phases and viability, which are indicative of cancer-driving behavior.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y762F

Genes: 2261

Variants: K652E S249C Y762F

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 22

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the S249C+Y762F FGFR3 mutant protein's ability to induce morphological transformation and increased proliferation in NIH-3T3 cells, indicating its role in tumor development or progression. Functional: The passage describes how the S249C+Y762F mutation affects the phosphorylation of PLCgamma1 and alters the activation of downstream signaling pathways, demonstrating a change in molecular function.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y762F

Genes: 2261

Variants: K652E S249C Y762F

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the K652E, S249C, and Y375C mutations alter the signaling response to FGF1 treatment, indicating that these variants affect molecular function related to phosphorylation and activation of signaling pathways. Oncogenic: The context of the mutations being discussed in relation to their effects on signaling pathways suggests that they may contribute to tumor development or progression, particularly given the focus on their responses in cancer-related cellular contexts.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the response of cells expressing mutant FGFR3 variants (S249C, Y375C, K652E) to FGF1 stimulation, indicating a correlation with receptor activation and signaling, which relates to treatment response. Functional: The passage describes how the variants S249C, Y375C, and K652E affect the phosphorylation of FGFR3, indicating that these mutations alter the molecular function of the receptor in response to ligand stimulation.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the increased phosphorylation of PLCgamma1 specifically in cells expressing the S249C and Y375C FGFR3 variants, indicating that these variants alter molecular function. Oncogenic: The mention of increased phosphorylation of signaling proteins in cells expressing the FGFR3 mutants suggests that these variants contribute to tumor development or progression.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the K652E, S249C, and Y375C variants of FGFR3 alter phosphorylation levels and dimerization behavior, indicating changes in molecular function. Oncogenic: The variants are described in the context of their constitutive activation and behavior in urothelial cells, suggesting their role in tumor development or progression.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the expression of proteins involved in cell survival and suggests that the K652E variant may alter the viability of cells, indicating a change in molecular function. Oncogenic: The context implies that the K652E variant contributes to tumor behavior by affecting cell viability, which is a characteristic of oncogenic variants.

Gene→Variant (gene-first): 2261:K652E

Genes: 2261

Variants: K652E

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants S249C, Y375C, and K652E FGFR3 alter the expression and phosphorylation of cell cycle-related proteins, indicating a change in molecular function.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the viability of cells expressing specific variants (S249C and Y375C) compared to controls, indicating that these variants alter the molecular or biochemical function of FGFR3, affecting cell viability. Oncogenic: The evidence suggests that the variants S249C and Y375C contribute to tumor development or progression by enhancing cell viability, which is a characteristic of oncogenic behavior.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Justification: Functional: The mention of K652E and Y375C variants also suggests alterations in cell cycle profiles, indicating a change in molecular function related to cell cycle dynamics.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 6

Evidence Type(s): Diagnostic, Functional

Justification: Diagnostic: The passage discusses the relative frequencies of the mutations K652E, S249C, and Y375C in bladder tumors, indicating an association with the disease. Functional: The passage mentions the phenotypic effects of the variants, suggesting that they alter the behavior of cells expressing these mutations compared to controls.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the expression of mutant FGFR3 variants S249C and Y375C alters the saturation density and morphology of normal urothelial cells, indicating a change in molecular or biochemical function. Oncogenic: The expression of the mutant FGFR3 variants is associated with changes in cell behavior, such as increased saturation density and altered morphology, which suggests a contribution to tumor development or progression.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the ability of the FGFR3 mutations (S249C, Y375C, and K652E) to transform NIH-3T3 cells, indicating that these somatic variants contribute to tumor development or progression. Functional: The passage describes how the FGFR3 mutations alter molecular function, specifically through increased phosphorylation of various proteins and changes in cell morphology and proliferation, demonstrating their biochemical activity.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC2789045 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the FGFR3 mutations (S249C, Y375C, and K652E) alter molecular signaling pathways, specifically the phosphorylation of various proteins, indicating a change in biochemical function. Oncogenic: The passage describes how the mutant FGFR3 variants induce morphological transformation, cell proliferation, and anchorage-independent growth, which are indicative of their role in tumor development and progression.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C