[Paper-level Aggregated] PMCID: PMC3378484

Evidence Type(s): Functional

Summary: Mutation: N564D | Summary: The N564D mutation is associated with altered lipid binding activities, displaying high levels of hydrophobic interaction with neutral lipids in the basal state, and modifying polar contacts in the C2 domain, which may influence interactions with phospholipid headgroups.

Evidence Type: Functional Mutation: K942 | Summary: The mutation K942 is important for p110gamma recognizing the substrate PtdIns(4,5)P2 head group, indicating that it alters molecular or biochemical function.

Evidence Type: Functional Mutation: R949 | Summary: The mutation R949 is important in the recognition of the substrate PtdIns(4,5)P2 head group, suggesting it alters molecular or biochemical function. The R949D variant shows much reduced binding to anionic lipids, indicating an alteration in molecular function related to lipid interactions.

Evidence Type: Functional Mutation: deletion of residues 1051-1068 | Summary: The deletion of residues 1051-1068 in p110alpha alters its molecular function by abrogating lipid kinase activity and lipid binding, indicating its functional importance.

Evidence Type: Functional Mutation: D915N | Summary: The D915N mutation in the catalytic DRH motif of p110alpha is associated with altered molecular function, specifically in the context of lipid binding and activation of the p110/p85 complex.

Evidence Type: Functional Mutation: K942Q | Summary: The K942Q mutation is associated with altered lipid binding properties, indicating a change in molecular function related to lipid interactions.

Evidence Type: Functional Mutation: C420R | Summary: The C420R mutation alters molecular function by displaying high levels of hydrophobic interaction with neutral lipids in the basal state and modifies molecular interactions within the C2 domain, potentially affecting lipid binding due to changes in hydrophobicity.

Evidence Type: Functional Mutation: E545K | Summary: The E545K mutation alters molecular function by displaying high levels of hydrophobic interaction with neutral lipids in the basal state and disrupts contacts in the C2/helical-nSH2 region, potentially exposing hydrophobic areas that could affect lipid binding.

Evidence Type: Functional Mutation: G1049R | Summary: The G1049R mutation alters molecular function by exhibiting high levels of hydrophobic and electrostatic binding to lipids upon phosphopeptide activation.

Evidence Type: Functional Mutation: H1047L | Summary: The H1047L mutation alters molecular function by exhibiting high levels of hydrophobic and electrostatic binding to lipids upon phosphopeptide activation and shows increased lipid binding levels compared to other p110 isoforms.

Evidence Type: Functional Mutation: H1047R | Summary: The H1047R mutation alters molecular function by exhibiting high levels of hydrophobic and electrostatic binding to lipids upon phosphopeptide activation, induces a global conformational change that may impact the molecular activity of the kinase C-lobe, and suggests a functional alteration in its biochemical properties.

Evidence Type: Functional Mutation: H1047 | Summary: The mutation H1047 is associated with altered lipid binding capabilities among the p110 isoforms, indicating a change in molecular function.

Gene→Variant (gene-first): PIK3R1(5295):N564D PIK3CG(5294):K942 PIK3CG(5294):R949 PIK3CA(5290):deletion of residues 1051-1068 PIK3CA(5290):D915N PIK3CG(5294):K942Q PIK3CA(5290):C420R PIK3CA(5290):E545K PIK3CA(5290):G1049R PIK3CA(5290):H1047L PIK3CA(5290):H1047R PIK3CA(5290):H1047

Genes: PIK3R1(5295) PIK3CG(5294) PIK3CA(5290)

Variants: N564D K942 R949 deletion of residues 1051-1068 D915N K942Q C420R E545K G1049R H1047L H1047R H1047

[Paper-level Aggregated] PMCID: PMC3378484

Evidence Type(s): Oncogenic

Summary: Mutation: E545K | Summary: The E545K mutation shows the highest basal activity and lipid binding, mimicking the activated wild-type p110alpha, indicating its role in tumor development. It is described as activating, suggesting it plays a role in tumor development or progression.

Evidence Type: Oncogenic Mutation: H1047R | Summary: The H1047R mutant exhibits increased basal kinase activities and lipid binding, contributing to tumor progression. It is described as an oncogenic mutant, indicating its contribution to tumor development or progression. The mutation is characterized as activating, suggesting it plays a role in tumor development or progression.

Evidence Type: Oncogenic Mutation: C420R | Summary: The C420R mutation shows increased basal kinase activity and lipid binding, suggesting its involvement in oncogenesis. It is characterized as activating, indicating its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: M1043I | Summary: The M1043I mutation is associated with increased basal kinase activity and lipid binding, indicating its oncogenic potential. It is noted to be activating, which implies its involvement in tumor development or progression.

Evidence Type: Oncogenic Mutation: H1047L | Summary: The H1047L mutation demonstrates increased basal kinase activity and lipid binding, contributing to tumor development. It is characterized as activating, indicating its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: G1049R | Summary: The G1049R mutation shows increased basal kinase activity and lipid binding, suggesting its role in oncogenesis. It is noted to be activating, which implies its involvement in tumor development or progression.

Evidence Type: Oncogenic Mutation: D915N | Summary: The D915N mutation is described as a cancer-linked mutation, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): PIK3CA(5290):E545K PIK3CA(5290):H1047R PIK3CA(5290):C420R PIK3CA(5290):M1043I PIK3CA(5290):H1047L PIK3CA(5290):G1049R PIK3CA(5290):D915N

Genes: PIK3CA(5290)

Variants: E545K H1047R C420R M1043I H1047L G1049R D915N

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 24

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: H1047 | Summary: The mutation H1047 is associated with altered lipid binding capabilities among the p110 isoforms, indicating a change in molecular function. Evidence Type: Functional | Mutation: H1047L | Summary: The mutation H1047L shows increased lipid binding levels compared to other p110 isoforms, suggesting a modification in biochemical function.

Gene→Variant (gene-first): 5290:H1047 5290:H1047L

Genes: 5290

Variants: H1047 H1047L

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 22

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: H1047R | Summary: The H1047R mutation in p110alpha appears to induce a global conformational change that may impact the molecular activity of the kinase C-lobe, suggesting a functional alteration in its biochemical properties.

Gene→Variant (gene-first): 5290:H1047R

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C420R | Summary: The C420R mutation alters the molecular interactions within the C2 domain, potentially affecting lipid binding due to changes in hydrophobicity. Evidence Type: Functional | Mutation: N564D | Summary: The N564D mutation modifies the polar contacts in the C2 domain, which may influence the interaction with phospholipid headgroups. Evidence Type: Functional | Mutation: E545K | Summary: The E545K mutation disrupts contacts in the C2/helical-nSH2 region, potentially exposing hydrophobic areas that could affect lipid binding.

Gene→Variant (gene-first): 5290:C420 5290:C420R 5290:E545K 5295:N345 5295:N564 5295:N564D

Genes: 5290 5295

Variants: C420 C420R E545K N345 N564 N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 19

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: G1049R | Summary: The G1049R mutation alters molecular function by exhibiting high levels of hydrophobic and electrostatic binding to lipids upon phosphopeptide activation. Evidence Type: Functional | Mutation: H1047L | Summary: The H1047L mutation alters molecular function by exhibiting high levels of hydrophobic and electrostatic binding to lipids upon phosphopeptide activation. Evidence Type: Functional | Mutation: H1047R | Summary: The H1047R mutation alters molecular function by exhibiting high levels of hydrophobic and electrostatic binding to lipids upon phosphopeptide activation.

Gene→Variant (gene-first): 5290:G1049R 5290:H1047L 5290:H1047R

Genes: 5290

Variants: G1049R H1047L H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 18

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C420R | Summary: The C420R mutation alters molecular function by displaying high levels of hydrophobic interaction with neutral lipids in the basal state. Evidence Type: Functional | Mutation: E545K | Summary: The E545K mutation alters molecular function by displaying high levels of hydrophobic interaction with neutral lipids in the basal state. Evidence Type: Functional | Mutation: N564D | Summary: The N564D mutation alters molecular function by displaying high levels of hydrophobic interaction with neutral lipids in the basal state.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5295:N564D

Genes: 5290 5295

Variants: C420R E545K N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E545K | Summary: The E545K mutation is associated with enhanced lipid binding and increased basal activity, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: C420R | Summary: The C420R mutation is characterized as activating, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: E545K | Summary: The E545K mutation is described as activating, suggesting it plays a role in tumor development or progression. Evidence Type: Oncogenic | Mutation: G1049R | Summary: The G1049R mutation is noted to be activating, which implies its involvement in tumor development or progression. Evidence Type: Oncogenic | Mutation: H1047L | Summary: The H1047L mutation is characterized as activating, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation is described as activating, suggesting it plays a role in tumor development or progression. Evidence Type: Oncogenic | Mutation: M1043I | Summary: The M1043I mutation is noted to be activating, which implies its involvement in tumor development or progression.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5290:G1049R 5290:H1047L 5290:H1047R 5290:M1043I 5295:N564D

Genes: 5290 5295

Variants: C420R E545K G1049R H1047L H1047R M1043I N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K942Q | Summary: The K942Q mutation is associated with altered lipid binding properties, indicating a change in molecular function related to lipid interactions. Evidence Type: Functional | Mutation: R949D | Summary: The R949D mutation shows much reduced binding to anionic lipids, suggesting an alteration in molecular function related to lipid interactions.

Gene→Variant (gene-first): 5294:K942Q 5294:R949D

Genes: 5294

Variants: K942Q R949D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: D915N | Summary: The D915N mutation in the catalytic DRH motif of p110alpha is associated with altered molecular function, specifically in the context of lipid binding and activation of the p110/p85 complex. Evidence Type: Oncogenic | Mutation: D915N | Summary: The D915N mutation is described as a cancer-linked mutation, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 5290:D915N

Genes: 5290

Variants: D915N

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: deletion of residues 1051-1068 | Summary: The deletion of residues 1051-1068 in p110alpha alters its molecular function by abrogating lipid kinase activity and lipid binding, indicating its functional importance.

Gene→Variant (gene-first): 5290:deletion of residues 1051-1068

Genes: 5290

Variants: deletion of residues 1051-1068

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation in p110alpha is described as an oncogenic mutant, indicating its contribution to tumor development or progression. Evidence Type: Functional | Mutation: H1047R | Summary: The passage discusses structural features of the H1047R mutant, suggesting that this variant alters molecular or biochemical function, particularly in relation to its conformation and interactions within the protein structure.

Gene→Variant (gene-first): 5290:H1047R

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K942 | Summary: The mutation K942 is described as being important for p110gamma recognizing the substrate PtdIns(4,5)P2 head group, indicating that it alters molecular or biochemical function. Evidence Type: Functional | Mutation: R949 | Summary: The mutation R949 is also noted for its importance in the recognition of the substrate PtdIns(4,5)P2 head group, suggesting it alters molecular or biochemical function.

Gene→Variant (gene-first): 5294:K942 5294:R949

Genes: 5294

Variants: K942 R949

[Paragraph-level] PMCID: PMC3378484 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: E545K | Summary: The E545K mutant shows the highest basal activity and lipid binding, mimicking the activated wild-type p110alpha, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutant exhibits increased basal kinase activities and lipid binding, contributing to tumor progression. Evidence Type: Oncogenic | Mutation: C420R | Summary: The C420R mutation shows increased basal kinase activity and lipid binding, suggesting its involvement in oncogenesis. Evidence Type: Oncogenic | Mutation: M1043I | Summary: The M1043I mutation is associated with increased basal kinase activity and lipid binding, indicating its oncogenic potential. Evidence Type: Oncogenic | Mutation: H1047L | Summary: The H1047L mutation demonstrates increased basal kinase activity and lipid binding, contributing to tumor development. Evidence Type: Oncogenic | Mutation: G1049R | Summary: The G1049R mutation shows increased basal kinase activity and lipid binding, suggesting its role in oncogenesis. Evidence Type: Functional | Mutation: N564D | Summary: The N564D mutation is associated with altered lipid binding activities, indicating a change in molecular function.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5290:G1049R 5290:H1047L 5290:H1047R 5290:M1043I 5295:N564D

Genes: 5290 5295

Variants: C420R E545K G1049R H1047L H1047R M1043I N564D

[Paper-level Aggregated] PMCID: PMC3378484

Evidence Type(s): Oncogenic, Functional, Predictive, Prognostic

Justification: Oncogenic: The text discusses somatic mutations in PIK3CA, including several specific variants (e.g., E545K, H1047R, C420R) that are characterized as activating mutations associated with increased lipid kinase activity, which is a hallmark of oncogenic mutations in cancer. Functional: The evidence indicates that specific mutations (e.g., C420R, E545K, H1047R) enhance lipid binding and kinase activity, demonstrating a functional impact on the protein's activity and its role in signaling pathways. Predictive: The text suggests that the presence of certain mutations correlates with enhanced lipid binding and kinase activity, which could be used to predict the functional outcomes of these mutations in cancer contexts. Prognostic: The correlation between specific mutations and increased lipid kinase activity implies that these mutations could serve as prognostic markers for cancer progression and response to therapies targeting the PI3K pathway.

Gene→Variant (gene-first): PIK3CA(5290):C420 PIK3CA(5290):C420R PIK3CA(5290):E545K PIK3R1(5295):N345 PIK3R1(5295):N564 PIK3R1(5295):N564D PIK3CA(5290):G1049R PIK3CA(5290):H1047L PIK3CA(5290):H1047R PIK3CA(5290):M1043I PIK3CA(5290):D915N PIK3CA(5290):H1047 PIK3CG(5294):K942 PIK3CG(5294):R949 PIK3CG(5294):K942Q PIK3CG(5294):R949D PIK3CA(5290):deletion of residues 1051-1068

Genes: PIK3CA(5290) PIK3R1(5295) PIK3CG(5294)

Variants: C420 C420R E545K N345 N564 N564D G1049R H1047L H1047R M1043I D915N H1047 K942 R949 K942Q R949D deletion of residues 1051-1068

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 24

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variant H1047L alters the lipid binding capabilities of the p110alpha isoform, indicating a change in molecular function.

Gene→Variant (gene-first): 5290:H1047 5290:H1047L

Genes: 5290

Variants: H1047 H1047L

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 22

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the H1047R variant leads to a global conformational change in the p110alpha/p85alpha structure, suggesting that it alters molecular function and potentially impacts activity. Oncogenic: The context implies that the H1047R variant contributes to tumor development or progression through its role in altering the conformational dynamics of the kinase, which is relevant in cancer biology.

Gene→Variant (gene-first): 5290:H1047R

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants C420R and N564D alter the molecular interactions within the C2 domain, suggesting changes in lipid binding capabilities, which indicates an alteration in biochemical function.

Gene→Variant (gene-first): 5290:C420 5290:C420R 5290:E545K 5295:N345 5295:N564 5295:N564D

Genes: 5290 5295

Variants: C420 C420R E545K N345 N564 N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 19

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants G1049R, H1047L, and H1047R alter binding properties to lipids, indicating a change in molecular function related to lipid binding upon activation.

Gene→Variant (gene-first): 5290:G1049R 5290:H1047L 5290:H1047R

Genes: 5290

Variants: G1049R H1047L H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 18

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the mutations (C420R, E545K, and N564D) alter the hydrophobic interaction with neutral lipids, indicating a change in molecular function related to lipid binding.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5295:N564D

Genes: 5290 5295

Variants: C420R E545K N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 17

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the E545K variant alters lipid kinase activity and lipid binding, indicating a change in molecular function.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage discusses mutations that are characterized as activating, indicating that they contribute to tumor development or progression.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5290:G1049R 5290:H1047L 5290:H1047R 5290:M1043I 5295:N564D

Genes: 5290 5295

Variants: C420R E545K G1049R H1047L H1047R M1043I N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the K942Q and R949D variants alter molecular function, specifically their effects on kinase activity and lipid binding, indicating changes in biochemical properties.

Gene→Variant (gene-first): 5294:K942Q 5294:R949D

Genes: 5294

Variants: K942Q R949D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the D915N mutation in the context of its role in lipid binding and activation of p110alpha, indicating that it alters molecular function related to protein activity. Oncogenic: The mention of "cancer-linked mutations" suggests that the D915N variant is associated with tumor development or progression, as it is discussed in the context of p110alpha, which is implicated in cancer.

Gene→Variant (gene-first): 5290:D915N

Genes: 5290

Variants: D915N

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the deletion of residues 1051-1068 alters the lipid kinase activity and ATPase activity of p110alpha, indicating a change in molecular function.

Gene→Variant (gene-first): 5290:deletion of residues 1051-1068

Genes: 5290

Variants: deletion of residues 1051-1068

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the oncogenic mutant H1047R p110alpha, indicating that this variant is associated with tumor development or progression, particularly in the context of its structural characteristics compared to the wild-type. Functional: The passage describes how the H1047R variant affects the conformation of the C-terminal tail and its interactions, suggesting alterations in molecular or biochemical function related to the protein's structure.

Gene→Variant (gene-first): 5290:H1047R

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional

Justification: Functional: The passage discusses key conserved activation loop residues K942 and R949 and their importance in recognizing the substrate, indicating that these variants alter molecular function related to substrate binding.

Gene→Variant (gene-first): 5294:K942 5294:R949

Genes: 5294

Variants: K942 R949

[Paragraph-level] PMCID: PMC3378484 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses somatic missense mutations in PIK3CA that contribute to increased kinase activities and lipid binding, indicating their role in tumor development or progression. Functional: The passage describes how specific mutations alter the molecular function of the p110alpha protein, including increased basal activity and lipid binding, which are indicative of changes in biochemical function.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5290:G1049R 5290:H1047L 5290:H1047R 5290:M1043I 5295:N564D

Genes: 5290 5295

Variants: C420R E545K G1049R H1047L H1047R M1043I N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 24

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variant H1047L alters the lipid binding capabilities of the p110alpha isoform, indicating a change in molecular function.

Gene→Variant (gene-first): 5290:H1047 5290:H1047L

Genes: 5290

Variants: H1047 H1047L

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 22

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the H1047R variant leads to a global conformational change in the p110alpha/p85alpha structure, suggesting that it alters molecular function and potentially impacts activity. Oncogenic: The context implies that the H1047R variant contributes to tumor development or progression through its role in altering the conformational dynamics of the kinase, which is relevant in cancer biology.

Gene→Variant (gene-first): 5290:H1047R

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants C420R and N564D alter the molecular interactions within the C2 domain, suggesting changes in lipid binding capabilities, which indicates an alteration in biochemical function.

Gene→Variant (gene-first): 5290:C420 5290:C420R 5290:E545K 5295:N345 5295:N564 5295:N564D

Genes: 5290 5295

Variants: C420 C420R E545K N345 N564 N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 19

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants G1049R, H1047L, and H1047R alter binding properties to lipids, indicating a change in molecular function related to lipid binding upon activation.

Gene→Variant (gene-first): 5290:G1049R 5290:H1047L 5290:H1047R

Genes: 5290

Variants: G1049R H1047L H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 18

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the mutations (C420R, E545K, and N564D) alter the hydrophobic interaction with neutral lipids, indicating a change in molecular function related to lipid binding.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5295:N564D

Genes: 5290 5295

Variants: C420R E545K N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 17

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the E545K variant alters lipid kinase activity and lipid binding, indicating a change in molecular function.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage discusses mutations that are characterized as activating, indicating that they contribute to tumor development or progression.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5290:G1049R 5290:H1047L 5290:H1047R 5290:M1043I 5295:N564D

Genes: 5290 5295

Variants: C420R E545K G1049R H1047L H1047R M1043I N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the K942Q and R949D variants alter molecular function, specifically their effects on kinase activity and lipid binding, indicating changes in biochemical properties.

Gene→Variant (gene-first): 5294:K942Q 5294:R949D

Genes: 5294

Variants: K942Q R949D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the D915N mutation in the context of its role in lipid binding and activation of p110alpha, indicating that it alters molecular function related to protein activity. Oncogenic: The mention of "cancer-linked mutations" suggests that the D915N variant is associated with tumor development or progression, as it is discussed in the context of p110alpha, which is implicated in cancer.

Gene→Variant (gene-first): 5290:D915N

Genes: 5290

Variants: D915N

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the deletion of residues 1051-1068 alters the lipid kinase activity and ATPase activity of p110alpha, indicating a change in molecular function.

Gene→Variant (gene-first): 5290:deletion of residues 1051-1068

Genes: 5290

Variants: deletion of residues 1051-1068

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the oncogenic mutant H1047R p110alpha, indicating that this variant is associated with tumor development or progression, particularly in the context of its structural characteristics compared to the wild-type. Functional: The passage describes how the H1047R variant affects the conformation of the C-terminal tail and its interactions, suggesting alterations in molecular or biochemical function related to the protein's structure.

Gene→Variant (gene-first): 5290:H1047R

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional

Justification: Functional: The passage discusses key conserved activation loop residues K942 and R949 and their importance in recognizing the substrate, indicating that these variants alter molecular function related to substrate binding.

Gene→Variant (gene-first): 5294:K942 5294:R949

Genes: 5294

Variants: K942 R949

[Paragraph-level] PMCID: PMC3378484 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses somatic missense mutations in PIK3CA that contribute to increased kinase activities and lipid binding, indicating their role in tumor development or progression. Functional: The passage describes how specific mutations alter the molecular function of the p110alpha protein, including increased basal activity and lipid binding, which are indicative of changes in biochemical function.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5290:G1049R 5290:H1047L 5290:H1047R 5290:M1043I 5295:N564D

Genes: 5290 5295

Variants: C420R E545K G1049R H1047L H1047R M1043I N564D