[Paper-level Aggregated] PMCID: PMC5491373

Evidence Type(s): Functional

Summary: Mutation: L320S | Summary: The L320S mutation alters the molecular function of the PTEN protein by decreasing its stability, affecting its localization, and inhibiting its ability to suppress AKT phosphorylation. It also creates a new potential phosphorylation site, impacts PTEN's conformation, and alters its interaction with the membrane-bound regulatory interface, leading to increased ubiquitination.

Evidence Type: Functional Mutation: T277A | Summary: The T277A mutation alters the molecular function of the PTEN protein by decreasing its stability, impacting its localization, and inhibiting its ability to suppress AKT phosphorylation. It affects PTEN's conformation, alters its ubiquitination, and modifies the interaction between the membrane-binding regulatory interface and the C-terminal tail of PTEN.

Evidence Type: Functional Mutation: K13 | Summary: The K13 mutation is involved in blocking ubiquitination, which affects PTEN stability and its degradation process, suggesting a functional alteration.

Evidence Type: Functional Mutation: K13R | Summary: The K13R mutation blocks ubiquitination at K13, impacting PTEN stability and its biochemical function.

Evidence Type: Functional Mutation: C124S | Summary: The C124S mutation stabilizes PTEN by presumably inhibiting its enzymatic activity, indicating a change in molecular function.

Evidence Type: Functional Mutation: T366 | Summary: Phosphorylation at T366 is shown to destabilize the PTEN protein, suggesting a functional impact on its molecular behavior.

Evidence Type: Functional Mutation: S370 | Summary: Phosphorylation at S370 contributes to the destabilization of the PTEN protein, indicating a change in its molecular function.

Evidence Type: Functional Mutation: T366A | Summary: The T366A mutation is part of constructs that were tested for stability, indicating its role in altering the molecular function of PTEN.

Evidence Type: Functional Mutation: S370A | Summary: The S370A mutation is included in constructs that failed to stabilize PTEN, suggesting an impact on its molecular function.

Evidence Type: Functional Mutation: F273 | Summary: The F273 mutation is suggested to alter the molecular function of PTEN by affecting its conformation and localization.

Evidence Type: Functional Mutation: F273A | Summary: The F273A mutation shows altered inhibition on nuclear accumulation and membrane localization, indicating a change in molecular function.

Evidence Type: Functional Mutation: F273L | Summary: The F273L mutation is involved in restoring the localization of PTEN, suggesting it impacts the molecular function of the protein.

Evidence Type: Functional Mutation: L320 | Summary: The L320 mutation is implicated in maintaining PTEN conformation necessary for its localization, indicating a functional role.

Evidence Type: Functional Mutation: L320A | Summary: The introduction of L320A into PTENA4 does not affect the strong inhibition of membrane and nuclear localization, indicating a functional role in PTEN's behavior.

Evidence Type: Functional Mutation: L320D | Summary: The phospho-mimetic mutation L320D does not show instabilities similar to those seen in PTENL320S, suggesting a functional difference in protein behavior.

Evidence Type: Functional Mutation: L320E | Summary: Similar to L320D, the phospho-mimetic mutation L320E does not exhibit instabilities like PTENL320S, indicating its functional impact on PTEN.

Evidence Type: Functional Mutation: T319 | Summary: The T319 residue is involved in phosphorylation by ROCK, suggesting it plays a role in the molecular function of PTEN.

Evidence Type: Functional Mutation: T319A | Summary: The T319A mutation does not enhance protein stability, indicating an alteration in the molecular function of PTEN.

Evidence Type: Functional Mutation: T321 | Summary: The T321 residue is involved in phosphorylation by ROCK, suggesting it plays a role in the molecular function of PTEN.

Evidence Type: Functional Mutation: T321A | Summary: The T321A mutation does not enhance protein stability, indicating an alteration in the molecular function of PTEN.

Evidence Type: Functional Mutation: Lys48 | Summary: The mutation Lys48 is involved in the formation of polyubiquitin chains, and its alteration affects the molecular function related to nuclear localization of the PTENL320S variant.

Evidence Type: Functional Mutation: K48R | Summary: The K48R mutation alters the molecular function of ubiquitin, affecting the localization and abundance of PTENL320S-GFP, indicating its role in nuclear accumulation and degradation processes.

Gene→Variant (gene-first): NEDD4(4734):L320S PTEN(5728):T277A GAPDH(2597):K13 GAPDH(2597):K13R PTEN(5728):C124S PTEN(5728):T366 PTEN(5728):S370 PTEN(5728):T366A PTEN(5728):S370A PIK3R1(5295):F273 PIK3R1(5295):F273A PIK3R1(5295):F273L NEDD4(4734):L320 NEDD4(4734):L320A NEDD4(4734):L320D NEDD4(4734):L320E PTEN(5728):T319 PTEN(5728):T319A PTEN(5728):T321 PTEN(5728):T321A PTEN(5728):Lys48 PTEN(5728):K48R

Genes: NEDD4(4734) PTEN(5728) GAPDH(2597) PIK3R1(5295)

Variants: L320S T277A K13 K13R C124S T366 S370 T366A S370A F273 F273A F273L L320 L320A L320D L320E T319 T319A T321 T321A Lys48 K48R

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 31

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K13 | Summary: The substitution of K13 to arginine alters the molecular function of PTEN, blocking its redistribution to the nucleus.

Gene→Variant (gene-first): 2597:K13

Genes: 2597

Variants: K13

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 30

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K48R | Summary: The K48R mutation alters the molecular function of ubiquitin, affecting the localization and abundance of PTENL320S-GFP, indicating its role in nuclear accumulation and degradation processes.

Gene→Variant (gene-first): 5728:K48R

Genes: 5728

Variants: K48R

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 29

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: Lys48 | Summary: The mutation Lys48 is involved in the formation of polyubiquitin chains, and its alteration affects the molecular function related to nuclear localization of the PTENL320S variant.

Gene→Variant (gene-first): 5728:Lys48

Genes: 5728

Variants: Lys48

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 26

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters the ability of the membrane-binding regulatory interface to interact with the C-terminal tail of PTEN, indicating a change in molecular function. Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation also affects the interaction between the membrane-binding regulatory interface and the C-terminal tail of PTEN, suggesting a modification in molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 25

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation alters molecular function by inhibiting the interaction between the membrane-bound regulatory interface and the C-terminus. Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters molecular function by inhibiting the interaction between the membrane-bound regulatory interface and the C-terminus.

Gene→Variant (gene-first): 4734:L320S

Genes: 4734

Variants: L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 24

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters the ubiquitination of PTEN, indicating a change in molecular function related to protein stability. Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation also affects the ubiquitination of PTEN, suggesting a modification in molecular function that impacts protein stability.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 23

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation alters the protein conformation and folding of PTEN, as evidenced by its susceptibility to trypsin digestion compared to wild-type PTEN. Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation affects the protein conformation and folding of PTEN, demonstrated by its lower half-lives during trypsin digestion relative to wild-type PTEN.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 22

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: F273 | Summary: The F273 mutation is suggested to alter the molecular function of PTEN by affecting its conformation and localization. Evidence Type: Functional | Mutation: F273A | Summary: The F273A mutation shows altered inhibition on nuclear accumulation and membrane localization, indicating a change in molecular function. Evidence Type: Functional | Mutation: F273L | Summary: The F273L mutation is involved in restoring the localization of PTEN, suggesting it impacts the molecular function of the protein. Evidence Type: Functional | Mutation: L320 | Summary: The L320 mutation is implicated in maintaining PTEN conformation necessary for its localization, indicating a functional role. Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation shows altered inhibition similar to F273A, suggesting it affects the molecular function of PTEN. Evidence Type: Functional | Mutation: L320F | Summary: The L320F mutation is involved in restoring PTEN localization, indicating a change in its molecular function.

Gene→Variant (gene-first): 5295:F273 5295:F273A 5295:F273L 4734:L320 4734:L320F 4734:L320S

Genes: 5295 4734

Variants: F273 F273A F273L L320 L320F L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 21

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters the molecular conformation of PTEN, promoting its ubiquitination. Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation also affects the conformation of PTEN, leading to increased ubiquitination.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation affects phosphorylation at other sites on PTEN, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: T319 | Summary: The T319 residue is involved in phosphorylation by ROCK, suggesting it plays a role in the molecular function of PTEN. Evidence Type: Functional | Mutation: T319A | Summary: The T319A mutation does not enhance protein stability, indicating an alteration in the molecular function of PTEN. Evidence Type: Functional | Mutation: T321 | Summary: The T321 residue is involved in phosphorylation by ROCK, suggesting it plays a role in the molecular function of PTEN. Evidence Type: Functional | Mutation: T321A | Summary: The T321A mutation does not enhance protein stability, indicating an alteration in the molecular function of PTEN.

Gene→Variant (gene-first): 4734:L320S 5728:T319 5728:T319A 5728:T321 5728:T321A

Genes: 4734 5728

Variants: L320S T319 T319A T321 T321A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 19

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The substitution of L320 to S alters the molecular function of PTEN by creating a new potential phosphorylation site, which affects its stability and localization. Evidence Type: Functional | Mutation: L320A | Summary: The introduction of L320A into PTENA4 does not affect the strong inhibition of membrane and nuclear localization, indicating a functional role in PTEN's behavior. Evidence Type: Functional | Mutation: L320D | Summary: The phospho-mimetic mutation L320D does not show instabilities similar to those seen in PTENL320S, suggesting a functional difference in protein behavior. Evidence Type: Functional | Mutation: L320E | Summary: Similar to L320D, the phospho-mimetic mutation L320E does not exhibit instabilities like PTENL320S, indicating its functional impact on PTEN.

Gene→Variant (gene-first): 4734:L320 4734:L320A 4734:L320D 4734:L320E 4734:L320S

Genes: 4734

Variants: L320 L320A L320D L320E L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters PTEN's ability to localize to the plasma membrane, resulting in its retention in the cytosol and affecting its function in reducing AKT phosphorylation. Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation similarly inhibits PTEN's membrane localization, leading to its accumulation in the cytosol and potentially impacting its role in tumor suppression. Evidence Type: Functional | Mutation: K13R | Summary: The K13R mutation is involved in the context of PTEN localization studies, but specific functional impacts are not detailed in the passage.

Gene→Variant (gene-first): 2597:K13R 4734:L320S 5728:T277A

Genes: 2597 4734 5728

Variants: K13R L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation alters the molecular function by blocking PTEN membrane and nuclear localization. Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters the molecular function by blocking PTEN membrane and nuclear localization.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation is associated with altered stability of the PTEN protein, indicating a change in molecular function. Evidence Type: Functional | Mutation: T366 | Summary: Phosphorylation at T366 is shown to destabilize the PTEN protein, suggesting a functional impact on its molecular behavior. Evidence Type: Functional | Mutation: S370 | Summary: Phosphorylation at S370 contributes to the destabilization of the PTEN protein, indicating a change in its molecular function. Evidence Type: Functional | Mutation: T366A | Summary: The T366A mutation is part of constructs that were tested for stability, indicating its role in altering the molecular function of PTEN. Evidence Type: Functional | Mutation: S370A | Summary: The S370A mutation is included in constructs that failed to stabilize PTEN, suggesting an impact on its molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:S370 5728:S370A 5728:T366 5728:T366A

Genes: 4734 5728

Variants: L320S S370 S370A T366 T366A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation decreases the stability of PTEN and alters its interactions with the plasma membrane, indicating a change in molecular function. Evidence Type: Functional | Mutation: K13 | Summary: The K13 mutation is involved in blocking ubiquitination, which affects PTEN stability and its degradation process, suggesting a functional alteration. Evidence Type: Functional | Mutation: K13R | Summary: The K13R mutation blocks ubiquitination at K13, impacting PTEN stability and its biochemical function. Evidence Type: Functional | Mutation: C124S | Summary: The C124S mutation stabilizes PTEN by presumably inhibiting its enzymatic activity, indicating a change in molecular function.

Gene→Variant (gene-first): 5728:C124S 2597:K13 2597:K13R 4734:L320S

Genes: 5728 2597 4734

Variants: C124S K13 K13R L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The PTENL320S variant shows decreased activity to suppress AKT phosphorylation, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: T277A | Summary: The PTENT277A variant also demonstrates decreased activity to suppress AKT phosphorylation, suggesting a change in molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation was tested for its effect on enzymatic activity, showing lipid phosphatase activity indistinguishable from wild-type PTEN, indicating it does not alter molecular function. Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation was also tested for its effect on enzymatic activity, demonstrating lipid phosphatase activity similar to wild-type PTEN, suggesting it does not alter molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation alters the molecular function of the PTEN protein, as it is associated with decreased steady state levels and affects PTEN localization. Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation also alters the molecular function of the PTEN protein, leading to decreased steady state levels and impacting PTEN localization.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paper-level Aggregated] PMCID: PMC5491373

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

Justification: Functional: The text discusses how mutations L320S and T277A affect PTEN's enzymatic activity and its ability to suppress AKT phosphorylation, indicating a functional impact on PTEN's role in signaling pathways. Oncogenic: The mutations L320S and T277A are associated with a loss of PTEN function, which is critical in cancer biology, as PTEN is a tumor suppressor and its inactivation can lead to tumorigenesis. Predictive: The study suggests that specific mutations in PTEN can predict changes in protein stability and localization, which may influence the outcome of therapies targeting PTEN-related pathways. Prognostic: The presence of mutations like L320S and T277A in PTEN may serve as prognostic markers for cancer progression, given their impact on PTEN's function and localization, which are crucial for tumor suppression.

Gene→Variant (gene-first): PTEN(5728):C124S GAPDH(2597):K13 GAPDH(2597):K13R NEDD4(4734):L320S PIK3R1(5295):F273 PIK3R1(5295):F273A PIK3R1(5295):F273L NEDD4(4734):L320 NEDD4(4734):L320F PTEN(5728):T277A PTEN(5728):K48R NEDD4(4734):L320A NEDD4(4734):L320D NEDD4(4734):L320E PTEN(5728):S370 PTEN(5728):S370A PTEN(5728):T366 PTEN(5728):T366A PTEN(5728):T319 PTEN(5728):T319A PTEN(5728):T321 PTEN(5728):T321A PTEN(5728):Lys48

Genes: PTEN(5728) GAPDH(2597) NEDD4(4734) PIK3R1(5295)

Variants: C124S K13 K13R L320S F273 F273A F273L L320 L320F T277A K48R L320A L320D L320E S370 S370A T366 T366A T319 T319A T321 T321A Lys48

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 31

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the substitution of the lysine residue K13 alters the nuclear localization of PTEN, indicating a change in molecular function related to protein activity and localization.

Gene→Variant (gene-first): 2597:K13

Genes: 2597

Variants: K13

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 30

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the K48R mutation alters the molecular function of ubiquitin, affecting the localization and abundance of PTENL320S-GFP, indicating a change in biochemical activity.

Gene→Variant (gene-first): 5728:K48R

Genes: 5728

Variants: K48R

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 29

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variant Lys48 affects the molecular function of PTENL320S by influencing its nuclear localization, indicating a change in biochemical activity related to polyubiquitination.

Gene→Variant (gene-first): 5728:Lys48

Genes: 5728

Variants: Lys48

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 26

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants PTENT277A and PTENL320S alter the ability of the protein to interact with the C-terminal tail, indicating a change in molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 25

Evidence Type(s): Functional

Justification: Functional: The passage indicates that the L320S variant alters the interaction of a protein at the membrane-bound regulatory interface, suggesting a change in molecular function.

Gene→Variant (gene-first): 4734:L320S

Genes: 4734

Variants: L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 24

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants PTENT277A and PTENL320S alter the ubiquitination of the PTEN protein, indicating a change in molecular function related to protein stability.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 23

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants L320S and T277A alter the protein conformation and folding of PTEN, indicating a change in molecular function as demonstrated by the trypsin digestion assay.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 22

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the F273 and L320 variants interact and affect the localization and conformation of PTEN, indicating that these variants alter molecular function.

Gene→Variant (gene-first): 5295:F273 5295:F273A 5295:F273L 4734:L320 4734:L320F 4734:L320S

Genes: 5295 4734

Variants: F273 F273A F273L L320 L320F L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 21

Evidence Type(s): Functional

Justification: Functional: The passage indicates that the variants T277A and L320S alter the conformation of PTEN and promote ubiquitination, which suggests a change in molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the mutations T319A and T321A do not enhance protein stability or membrane localization of PTENL320S, indicating that these variants alter molecular function related to protein activity and localization.

Gene→Variant (gene-first): 4734:L320S 5728:T319 5728:T319A 5728:T321 5728:T321A

Genes: 4734 5728

Variants: L320S T319 T319A T321 T321A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 19

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the substitution of L320 to S affects the molecular function of PTEN, specifically its stability, localization, and phosphorylation status, indicating a change in biochemical function.

Gene→Variant (gene-first): 4734:L320 4734:L320A 4734:L320D 4734:L320E 4734:L320S

Genes: 4734

Variants: L320 L320A L320D L320E L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the T277A and L320S mutations alter the molecular function of PTEN by blocking its membrane localization and decreasing its ability to reduce AKT phosphorylation, indicating a change in biochemical activity. Oncogenic: The passage suggests that the nuclear localization defects caused by the T277A and L320S mutations could affect PTEN function in suppressing tumor formation, indicating that these mutations contribute to tumor development or progression.

Gene→Variant (gene-first): 2597:K13R 4734:L320S 5728:T277A

Genes: 2597 4734 5728

Variants: K13R L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Justification: Functional: The passage indicates that the L320S and T277A mutations alter the localization of the PTEN protein, which is a change in molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Justification: Functional: The passage discusses how specific phosphorylation events at the T366 and S370 sites affect the stability of the PTEN protein, indicating that these variants alter molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:S370 5728:S370A 5728:T366 5728:T366A

Genes: 4734 5728

Variants: L320S S370 S370A T366 T366A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the L320S variant decreases the stability of PTEN and its interactions with the plasma membrane, indicating an alteration in molecular function. Oncogenic: The context of the passage suggests that the variants, particularly L320S, contribute to tumor development or progression by affecting PTEN stability and function, which is relevant in cancer biology.

Gene→Variant (gene-first): 5728:C124S 2597:K13 2597:K13R 4734:L320S

Genes: 5728 2597 4734

Variants: C124S K13 K13R L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the PTEN variants L320S and T277A alter the molecular function of PTEN, specifically its ability to suppress AKT phosphorylation and inhibit cell migration and proliferation. Oncogenic: The variants PTENL320S and PTENT277A are implicated in decreased activity to suppress key signaling pathways and cellular behaviors associated with tumor development and progression, indicating their role in oncogenesis.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants L320S and T277A were tested for their effect on enzymatic activity, specifically lipid phosphatase activity, indicating that they alter molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the L320S and T277A mutations in PTEN alter the steady state levels of the proteins and their localization, indicating a change in molecular function. Oncogenic: The context suggests that the mutations contribute to the alteration of PTEN function, which is implicated in tumor development or progression.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A