36 Matching Annotations
  1. Mar 2026
  2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Untitled document
    14
    1. karimkhoury04 25 Mar 2026
      The HER2 S310F Mutant Can Form an Active Heterodimer with the EGFR, Which Can Be Inhibited by Cetuximab but Not by Trastuzumab as well as Pertuzumab

      [Paper-level Aggregated] PMCID: PMC6843359

      Evidence Type(s): Functional

      Summary: Mutation: S310F | Summary: The S310F mutation alters the reactivity and binding properties of the HER2 protein, affecting its interactions with specific antibodies and forming heterodimers with EGFR. This indicates a significant change in molecular and biochemical function, as evidenced by analyses in bladder cancer cell lines, including expression confirmation through immunoprecipitation and fluorescence intensity measurements.

      Gene→Variant (gene-first): ERBB2(2064):S310F

      Genes: ERBB2(2064)

      Variants: S310F

      CIViC paper-level aggregated PMC6843359 Functional
    2. karimkhoury04 25 Mar 2026
      The HER2 S310F Mutant Can Form an Active Heterodimer with the EGFR, Which Can Be Inhibited by Cetuximab but Not by Trastuzumab as well as Pertuzumab

      [Paper-level Aggregated] PMCID: PMC6843359

      Evidence Type(s): Oncogenic

      Summary: Mutation: S310F | Summary: The S310F mutation is associated with tumor development or progression, as it alters the molecular function of HER2, contributes to receptor activation, and is involved in the formation of active heterodimers with EGFR. Its expression in bladder cancer cell lines suggests a role in tumor development, and it is implicated in altered reactivity to therapeutic antibodies.

      Evidence Type: Oncogenic Mutation: G309A | Summary: The G309A mutation is associated with receptor activation in the HER2 extracellular domain, indicating its role in tumor development.

      Evidence Type: Oncogenic Mutation: G309E | Summary: The G309E mutation contributes to receptor activation in the HER2 extracellular domain, suggesting its involvement in tumor progression.

      Evidence Type: Oncogenic Mutation: S310 | Summary: The S310 mutation is implicated in receptor activation within the HER2 extracellular domain, indicating its potential role in oncogenesis.

      Evidence Type: Oncogenic Mutation: S310Y | Summary: The S310Y mutation is associated with receptor activation in the HER2 extracellular domain, indicating its role in tumor progression.

      Gene→Variant (gene-first): ERBB2(2064):S310F ERBB2(2064):G309A ERBB2(2064):G309E ERBB2(2064):S310 ERBB2(2064):S310Y

      Genes: ERBB2(2064)

      Variants: S310F G309A G309E S310 S310Y

      CIViC paper-level aggregated PMC6843359 Oncogenic
    3. karimkhoury04 25 Mar 2026
      The HER2 S310F Mutant Can Form an Active Heterodimer with the EGFR, Which Can Be Inhibited by Cetuximab but Not by Trastuzumab as well as Pertuzumab

      [Paper-level Aggregated] PMCID: PMC6843359

      Evidence Type(s): Predictive

      Summary: Mutation: S310F | Summary: The S310F mutant is not reactive to pertuzumab, indicating potential resistance to this therapy, while it retains binding to trastuzumab, suggesting a correlation with treatment response. Additionally, the S310F mutant's response to anti-HER2 agents, particularly the lack of effect from trastuzumab on cell proliferation, further supports its predictive role in therapy resistance.

      Evidence Type: Predictive Mutation: S309A | Summary: The S309A HER2 mutant reacted with trastuzumab with reduced affinity compared to wild-type HER2, indicating a correlation with therapy response.

      Evidence Type: Predictive Mutation: G309E | Summary: The G309E HER2 mutant did not bind to pertuzumab, indicating a potential resistance to this therapy.

      Evidence Type: Predictive Mutation: S310Y | Summary: The S310Y HER2 mutant did not bind to pertuzumab, suggesting a potential resistance to this therapy.

      Evidence Type: Predictive Mutation: G309 | Summary: The G309 HER2 mutants, including G309A and G309E, were tested for binding to pertuzumab, indicating their relevance in therapy response.

      Gene→Variant (gene-first): ERBB2(2064):S310F ERBB2(2064):S309A ERBB2(2064):G309E ERBB2(2064):S310Y ERBB2(2064):G309

      Genes: ERBB2(2064)

      Variants: S310F S309A G309E S310Y G309

      CIViC paper-level aggregated PMC6843359 Predictive
    4. karimkhoury04 25 Mar 2026
      G309 or S310 mutations on the HER2 extracellular domain II induce receptor activation. Clinically, S310F is most frequent among HER2 extracellular domain mutations and patients with the S310F mutation without HER2 amplif

      [Paragraph-level] PMCID: PMC6843359 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Oncogenic

      Summary: Evidence Type: Oncogenic | Mutation: G309A | Summary: The G309A mutation is associated with receptor activation in the HER2 extracellular domain, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: G309E | Summary: The G309E mutation contributes to receptor activation in the HER2 extracellular domain, suggesting its involvement in tumor progression. Evidence Type: Oncogenic | Mutation: S310 | Summary: The S310 mutation is implicated in receptor activation within the HER2 extracellular domain, indicating its potential role in oncogenesis. Evidence Type: Oncogenic | Mutation: S310F | Summary: The S310F mutation induces receptor activation and is involved in the formation of active heterodimers with EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: S310Y | Summary: The S310Y mutation is associated with receptor activation in the HER2 extracellular domain, indicating its role in tumor progression.

      Gene→Variant (gene-first): 2064:G309A 2064:G309E 2064:S310 2064:S310F 2064:S310Y

      Genes: 2064

      Variants: G309A G309E S310 S310F S310Y

      CIViC paragraph-level PMC6843359 Oncogenic
    5. karimkhoury04 25 Mar 2026
      After transfection, the cells were allowed to grow for 24 h and then lysed. The level of EGFR-mCherry and wild-type and S310F HER2-eGFP in the cell lysate was determined by measuring the fluorescence intensity. After a c

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 11

      Evidence Type(s): Functional

      Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F HER2 variant alters the interaction efficiency with EGFR, as indicated by the fluorescence intensity measurements in the cell lysates, suggesting a change in molecular function.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional
    6. karimkhoury04 25 Mar 2026
      Single molecule interaction analysis was performed to determine whether the S310F HER mutant formed a heterodimer with the EGFR. We constructed a bicistronic mammalian expression vector encoding EGFR-mCherry and S310F HE

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Functional, Oncogenic

      Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F HER2 mutant was analyzed for its ability to form a heterodimer with EGFR, indicating that it alters molecular interactions and functions in a cellular context. Evidence Type: Oncogenic | Mutation: S310F | Summary: The S310F HER2 mutation is implicated in altered reactivity to therapeutic antibodies, suggesting a role in tumor development or progression.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional Oncogenic
    7. karimkhoury04 25 Mar 2026
      3.4. Single-Molecular Interaction Analysis Demonstrated That the S310F HER2 Mutant Formed Heterodimers with the EGFR

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Functional

      Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F HER2 mutant alters molecular interactions by forming heterodimers with the EGFR, indicating a change in biochemical function.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional
    8. karimkhoury04 25 Mar 2026
      We tested the effects of anti-HER2 agents on 5637 cell proliferation and the level of HER2 phosphorylation at Y1221 and Y1222 residues. The cells were incubated with pertuzumab, trastuzumab and lapatinib for 96 h, lysed

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 8

      Evidence Type(s): Oncogenic, Predictive

      Summary: Evidence Type: Oncogenic | Mutation: S310F | Summary: The S310F HER2 mutant contributes to tumor development as indicated by its phosphorylation in response to EGFR signaling in 5637 cells. Evidence Type: Predictive | Mutation: S310F | Summary: The S310F HER2 mutant's response to anti-HER2 agents, particularly the lack of effect from trastuzumab on cell proliferation, suggests its predictive role in therapy resistance.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Oncogenic Predictive
    9. karimkhoury04 25 Mar 2026
      3.3. EGFR Activates S310F HER2 Mutant in 5637 Cell

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 7

      Evidence Type(s): Oncogenic

      Summary: Evidence Type: Oncogenic | Mutation: S310F | Summary: The S310F mutation is associated with tumor development or progression as indicated by its activation in the context of the HER2 mutant in cell studies.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Oncogenic
    10. karimkhoury04 25 Mar 2026
      To confirm the expression of the S310F HER2 mutant in 5637 cells, we used immunoprecipitation experiments. We hypothesized that if the cells expressed the S310F HER2 mutant, it would not be immunoprecipitated by pertuzum

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 6

      Evidence Type(s): Functional, Oncogenic

      Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F HER2 mutant was confirmed to be expressed in 5637 cells through immunoprecipitation experiments, indicating that the variant alters the molecular function of HER2. Evidence Type: Oncogenic | Mutation: S310F | Summary: The expression of the S310F HER2 mutant in 5637 cells suggests that this somatic variant may contribute to tumor development or progression.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional Oncogenic
    11. karimkhoury04 25 Mar 2026
      We searched literatures to identify a human cell line expressing the S310F mutant and found that bladder cancer cell line 5637 expressed the mutant. To test the allelic expression of the S310F HER2 mutant in the 5637 cel

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 5

      Evidence Type(s): Functional

      Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F mutation was identified in a bladder cancer cell line, and its expression was analyzed through molecular techniques, indicating an alteration in molecular function.

      Gene→Variant (gene-first): 2064:S310 2064:S310F

      Genes: 2064

      Variants: S310 S310F

      CIViC paragraph-level PMC6843359 Functional
    12. karimkhoury04 25 Mar 2026
      3.2. A Bladder Cancer Cell Line, 5637, Expresses Both Wild-Type HER2 and S310F Mutant

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 4

      Evidence Type(s): Functional, Oncogenic

      Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F mutation is mentioned in the context of a bladder cancer cell line, indicating that it alters the molecular or biochemical function of HER2. Evidence Type: Oncogenic | Mutation: S310F | Summary: The presence of the S310F mutation in a bladder cancer cell line suggests that it may contribute to tumor development or progression.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional Oncogenic
    13. karimkhoury04 25 Mar 2026
      A construct encoding the S310F HER2 extracellular domain fused to a human Fc domain of immunoglobulin heavy chain was prepared and cloned into a mammalian expression vector. For comparison, the expression vectors encodin

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 3

      Evidence Type(s): Predictive

      Summary: Evidence Type: Predictive | Mutation: S309A | Summary: The S309A HER2 mutant reacted with trastuzumab with reduced affinity compared to wild-type HER2, indicating a correlation with therapy response. Evidence Type: Predictive | Mutation: S310F | Summary: The S310F mutant did not bind to pertuzumab but reacted with trastuzumab in a dose-dependent manner, suggesting its role in therapy response. Evidence Type: Predictive | Mutation: G309E | Summary: The G309E HER2 mutant did not bind to pertuzumab, indicating a potential resistance to this therapy. Evidence Type: Predictive | Mutation: S310Y | Summary: The S310Y HER2 mutant did not bind to pertuzumab, suggesting a potential resistance to this therapy. Evidence Type: Predictive | Mutation: G309 | Summary: The G309 HER2 mutants, including G309A and G309E, were tested for binding to pertuzumab, indicating their relevance in therapy response.

      Gene→Variant (gene-first): 2064:G309 2064:G309A 2064:G309E 2064:S309A 2064:S310 2064:S310F 2064:S310Y

      Genes: 2064

      Variants: G309 G309A G309E S309A S310 S310F S310Y

      CIViC paragraph-level PMC6843359 Predictive
    14. karimkhoury04 25 Mar 2026
      3.1. The Recombinant S310F Mutant Is Not Reactive to Pertuzumab but Binds to Trastuzumab

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 2

      Evidence Type(s): Predictive, Functional

      Summary: Evidence Type: Predictive | Mutation: S310F | Summary: The S310F mutant is not reactive to Pertuzumab, indicating a potential resistance to this therapy, while it retains binding to Trastuzumab, suggesting a correlation with treatment response. Evidence Type: Functional | Mutation: S310F | Summary: The S310F mutation alters the reactivity of the protein, affecting its binding properties with specific antibodies, which indicates a change in molecular function.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Predictive Functional
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC6843359/pdf/biomolecules-09-00629.pdf
  3. Feb 2026
  4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Untitled document
    22
    1. karim2001khoury 19 Feb 2026
      The HER2 S310F Mutant Can Form an Active Heterodimer with the EGFR, Which Can Be Inhibited by Cetuximab but Not by Trastuzumab as well as Pertuzumab

      [Paper-level Aggregated] PMCID: PMC6843359

      Evidence Type(s): Oncogenic, Predictive, Functional

      Justification: Oncogenic: The S310F HER2 mutant is described as inducing receptor activation and forming active heterodimers with EGFR, suggesting its role in promoting cancer cell proliferation. Predictive: The text indicates that patients with the S310F mutation responded to trastuzumab with or without pertuzumab, suggesting that the presence of this mutation can predict treatment response. Functional: The S310F HER2 mutant's ability to interact with EGFR and its effects on HER2 phosphorylation and cell proliferation demonstrate its functional role in cellular signaling pathways.

      Gene→Variant (gene-first): ERBB2(2064):G309 ERBB2(2064):G309A ERBB2(2064):G309E ERBB2(2064):S309A ERBB2(2064):S310 ERBB2(2064):S310F ERBB2(2064):S310Y

      Genes: ERBB2(2064)

      Variants: G309 G309A G309E S309A S310 S310F S310Y

      CIViC paper-level aggregated PMC6843359
    2. karim2001khoury 19 Feb 2026
      G309 or S310 mutations on the HER2 extracellular domain II induce receptor activation. Clinically, S310F is most frequent among HER2 extracellular domain mutations and patients with the S310F mutation without HER2 amplif

      [Paragraph-level] PMCID: PMC6843359 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage discusses the response of patients with the S310F mutation to trastuzumab and pertuzumab treatments, indicating a correlation between the variant and treatment response. Functional: The passage describes how the S310F mutation alters the ability of the HER2 receptor to form homodimers or heterodimers and its interaction with EGFR, demonstrating a change in molecular function.

      Gene→Variant (gene-first): 2064:G309A 2064:G309E 2064:S310 2064:S310F 2064:S310Y

      Genes: 2064

      Variants: G309A G309E S310 S310F S310Y

      CIViC paragraph-level PMC6843359 Predictive Functional
    3. karim2001khoury 19 Feb 2026
      After transfection, the cells were allowed to grow for 24 h and then lysed. The level of EGFR-mCherry and wild-type and S310F HER2-eGFP in the cell lysate was determined by measuring the fluorescence intensity. After a c

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 11

      Evidence Type(s): Functional

      Justification: Functional: The passage discusses how the S310F variant of HER2 interacts with EGFR and compares its efficiency to wild-type HER2, indicating an alteration in molecular function.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional
    4. karim2001khoury 19 Feb 2026
      Single molecule interaction analysis was performed to determine whether the S310F HER mutant formed a heterodimer with the EGFR. We constructed a bicistronic mammalian expression vector encoding EGFR-mCherry and S310F HE

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the interaction of the S310F HER2 mutant with EGFR and its altered reactivity to specific antibodies, indicating a change in molecular function. Oncogenic: The S310F HER2 variant is implicated in altered interactions that may contribute to tumor development or progression, as suggested by the context of the study involving cancer-related proteins.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional Oncogenic
    5. karim2001khoury 19 Feb 2026
      3.4. Single-Molecular Interaction Analysis Demonstrated That the S310F HER2 Mutant Formed Heterodimers with the EGFR

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Functional

      Justification: Functional: The passage indicates that the S310F variant alters the molecular interaction by forming heterodimers with EGFR, suggesting a change in biochemical function.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional
    6. karim2001khoury 19 Feb 2026
      We tested the effects of anti-HER2 agents on 5637 cell proliferation and the level of HER2 phosphorylation at Y1221 and Y1222 residues. The cells were incubated with pertuzumab, trastuzumab and lapatinib for 96 h, lysed

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 8

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the effects of anti-HER2 agents on cell proliferation and HER2 phosphorylation in relation to the S310F HER2 mutant, indicating a correlation with response to specific therapies. Oncogenic: The S310F variant is implicated in the phosphorylation process and cell proliferation in cancer cells, suggesting its role in tumor development or progression.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Predictive Oncogenic
    7. karim2001khoury 19 Feb 2026
      3.3. EGFR Activates S310F HER2 Mutant in 5637 Cell

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 7

      Evidence Type(s): Oncogenic

      Justification: Oncogenic: The passage indicates that the S310F variant in HER2 is associated with activation in a cell line, suggesting its role in tumor development or progression.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Oncogenic
    8. karim2001khoury 19 Feb 2026
      To confirm the expression of the S310F HER2 mutant in 5637 cells, we used immunoprecipitation experiments. We hypothesized that if the cells expressed the S310F HER2 mutant, it would not be immunoprecipitated by pertuzum

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 6

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the expression of the S310F HER2 mutant and its interaction with pertuzumab, indicating that the variant alters the molecular function of HER2 in terms of immunoprecipitation. Oncogenic: The S310F variant is described in the context of its expression in cancer cell lines, suggesting that it may contribute to tumor development or progression.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional Oncogenic
    9. karim2001khoury 19 Feb 2026
      We searched literatures to identify a human cell line expressing the S310F mutant and found that bladder cancer cell line 5637 expressed the mutant. To test the allelic expression of the S310F HER2 mutant in the 5637 cel

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 5

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the expression and detection of the S310F HER2 mutant in a bladder cancer cell line, indicating that the variant alters the molecular function of the HER2 protein as it is being analyzed for its presence on the cell surface. Oncogenic: The S310F variant is discussed in the context of a bladder cancer cell line, suggesting that it may contribute to tumor development or progression, which aligns with the definition of an oncogenic variant.

      Gene→Variant (gene-first): 2064:S310 2064:S310F

      Genes: 2064

      Variants: S310 S310F

      CIViC paragraph-level PMC6843359 Functional Oncogenic
    11. karim2001khoury 19 Feb 2026
      A construct encoding the S310F HER2 extracellular domain fused to a human Fc domain of immunoglobulin heavy chain was prepared and cloned into a mammalian expression vector. For comparison, the expression vectors encodin

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 3

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage discusses the binding interactions of various HER2 mutants with the antibodies pertuzumab and trastuzumab, indicating their response to these therapies. Functional: The passage describes the preparation and purification of recombinant fusion proteins and their binding characteristics, which suggests alterations in molecular function related to the HER2 mutants.

      Gene→Variant (gene-first): 2064:G309 2064:G309A 2064:G309E 2064:S309A 2064:S310 2064:S310F 2064:S310Y

      Genes: 2064

      Variants: G309 G309A G309E S309A S310 S310F S310Y

      CIViC paragraph-level PMC6843359 Predictive Functional
    12. karim2001khoury 19 Feb 2026
      3.1. The Recombinant S310F Mutant Is Not Reactive to Pertuzumab but Binds to Trastuzumab

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 2

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage indicates that the S310F mutant is not reactive to Pertuzumab, suggesting a correlation with resistance to this specific therapy. Functional: The passage discusses the binding characteristics of the S310F mutant, indicating an alteration in molecular function related to its interaction with Trastuzumab.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Predictive Functional
    13. karim2001khoury 19 Feb 2026
      After transfection, the cells were allowed to grow for 24 h and then lysed. The level of EGFR-mCherry and wild-type and S310F HER2-eGFP in the cell lysate was determined by measuring the fluorescence intensity. After a c

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 11

      Evidence Type(s): Functional

      Justification: Functional: The passage discusses how the S310F variant of HER2 interacts with EGFR and compares its efficiency to wild-type HER2, indicating an alteration in molecular function.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional
    14. karim2001khoury 19 Feb 2026
      Single molecule interaction analysis was performed to determine whether the S310F HER mutant formed a heterodimer with the EGFR. We constructed a bicistronic mammalian expression vector encoding EGFR-mCherry and S310F HE

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the interaction of the S310F HER2 mutant with EGFR and its altered reactivity to specific antibodies, indicating a change in molecular function. Oncogenic: The S310F HER2 variant is implicated in altered interactions that may contribute to tumor development or progression, as suggested by the context of the study involving cancer-related proteins.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional Oncogenic
    15. karim2001khoury 19 Feb 2026
      3.4. Single-Molecular Interaction Analysis Demonstrated That the S310F HER2 Mutant Formed Heterodimers with the EGFR

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Functional

      Justification: Functional: The passage indicates that the S310F variant alters the molecular interaction by forming heterodimers with EGFR, suggesting a change in biochemical function.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional
    16. karim2001khoury 19 Feb 2026
      We tested the effects of anti-HER2 agents on 5637 cell proliferation and the level of HER2 phosphorylation at Y1221 and Y1222 residues. The cells were incubated with pertuzumab, trastuzumab and lapatinib for 96 h, lysed

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 8

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the effects of anti-HER2 agents on cell proliferation and HER2 phosphorylation in relation to the S310F HER2 mutant, indicating a correlation with response to specific therapies. Oncogenic: The S310F variant is implicated in the phosphorylation process and cell proliferation in cancer cells, suggesting its role in tumor development or progression.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Predictive Oncogenic
    17. karim2001khoury 19 Feb 2026
      3.3. EGFR Activates S310F HER2 Mutant in 5637 Cell

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 7

      Evidence Type(s): Oncogenic

      Justification: Oncogenic: The passage indicates that the S310F variant in HER2 is associated with activation in a cell line, suggesting its role in tumor development or progression.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Oncogenic
    18. karim2001khoury 19 Feb 2026
      To confirm the expression of the S310F HER2 mutant in 5637 cells, we used immunoprecipitation experiments. We hypothesized that if the cells expressed the S310F HER2 mutant, it would not be immunoprecipitated by pertuzum

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 6

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the expression of the S310F HER2 mutant and its interaction with pertuzumab, indicating that the variant alters the molecular function of HER2 in terms of immunoprecipitation. Oncogenic: The S310F variant is described in the context of its expression in cancer cell lines, suggesting that it may contribute to tumor development or progression.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Functional Oncogenic
    19. karim2001khoury 19 Feb 2026
      We searched literatures to identify a human cell line expressing the S310F mutant and found that bladder cancer cell line 5637 expressed the mutant. To test the allelic expression of the S310F HER2 mutant in the 5637 cel

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 5

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the expression and detection of the S310F HER2 mutant in a bladder cancer cell line, indicating that the variant alters the molecular function of the HER2 protein as it is being analyzed for its presence on the cell surface. Oncogenic: The S310F variant is discussed in the context of a bladder cancer cell line, suggesting that it may contribute to tumor development or progression, which aligns with the definition of an oncogenic variant.

      Gene→Variant (gene-first): 2064:S310 2064:S310F

      Genes: 2064

      Variants: S310 S310F

      CIViC paragraph-level PMC6843359 Functional Oncogenic
    21. karim2001khoury 19 Feb 2026
      A construct encoding the S310F HER2 extracellular domain fused to a human Fc domain of immunoglobulin heavy chain was prepared and cloned into a mammalian expression vector. For comparison, the expression vectors encodin

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 3

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage discusses the binding interactions of various HER2 mutants with the antibodies pertuzumab and trastuzumab, indicating their response to these therapies. Functional: The passage describes the preparation and purification of recombinant fusion proteins and their binding characteristics, which suggests alterations in molecular function related to the HER2 mutants.

      Gene→Variant (gene-first): 2064:G309 2064:G309A 2064:G309E 2064:S309A 2064:S310 2064:S310F 2064:S310Y

      Genes: 2064

      Variants: G309 G309A G309E S309A S310 S310F S310Y

      CIViC paragraph-level PMC6843359 Predictive Functional
    22. karim2001khoury 19 Feb 2026
      3.1. The Recombinant S310F Mutant Is Not Reactive to Pertuzumab but Binds to Trastuzumab

      [Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 2

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage indicates that the S310F mutant is not reactive to Pertuzumab, suggesting a correlation with resistance to this specific therapy. Functional: The passage discusses the binding characteristics of the S310F mutant, indicating an alteration in molecular function related to its interaction with Trastuzumab.

      Gene→Variant (gene-first): 2064:S310F

      Genes: 2064

      Variants: S310F

      CIViC paragraph-level PMC6843359 Predictive Functional
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC6843359/pdf/biomolecules-09-00629.pdf