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| Gene Symbol | PIK3CA | ||||||||||
| Synonyms | CCM4 | CLAPO | CLOVE | CWS5 | HMH | MCAP | MCM | MCMTC | p110-alpha | PI3K | PI3K-alpha | ||||||||||
| Gene Description | PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, activates PI3K/AKT/mTOR signaling to promote cell proliferation (PMID: 23411347, PMID: 31905960). PIK3CA activating mutations have been identified in a number of tumor types such as breast cancer (PMID: 32234362, PMID: 32404150), colon cancer (PMID: 32099598), endometrial cancer, glioblastoma, skin cancer, ovarian cancer (PMID: 20535651, PMID: 31892193), and mammary angiosarcoma (PMID: 32123305), and PIK3CA amplification has been observed in esophageal adenocarcinoma (PMID: 31865178). | ||||||||||
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| Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
|---|---|---|---|---|
| A1020V | missense | no effect | PIK3CA A1020V lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). A1020V demonstrates transformation potential and supports cell survival to similar level of wild-type Pik3ca protein in cell culture (PMID: 26627007, PMID: 29533785). | |
| A1035T | missense | unknown | PIK3CA A1035T lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). A1035T has been identified in the scientific literature (PMID: 33710807, PMID: 26796526), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| A1035V | missense | unknown | PIK3CA A1035V lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). A1035V has been identified in the scientific literature (PMID: 30167082, PMID: 28936923, PMID: 34269527), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| A1046E | missense | unknown | PIK3CA A1046E lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). A1046E has been identified in the scientific literature (PMID: 18022911, PMID: 22357840, PMID: 22753589), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| A1046T | missense | unknown | PIK3CA A1046T lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). A1046T has been identified in the scientific literature (PMID: 25150293, PMID: 22357840, PMID: 30546467), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| A1046V | missense | unknown | PIK3CA A1046V lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). A1046V has been identified in the scientific literature (PMID: 23107319, PMID: 26796526), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| A1046_H1047insTSA | insertion | unknown | PIK3CA A1046_H1047insTSA results in the insertion of three amino acids in the PI3K/PI4K domain of the Pik3ca protein between amino acids 1046 and 1047 (UniProt.org). A1046_H1047insTSA has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| A1066V | missense | unknown | PIK3CA A1066V does not lie within any known functional domains of the Pik3ca protein (UniProt.org). A1066V results in Akt phosphorylation levels similar to wild-type Pik3ca, but results in increased anchorage-independent colony formation and cell motility in conditions without growth factor in cell culture (PMID: 22430209), and therefore, its effect on Pik3ca protein function is unknown. | |
| act mut | unknown | gain of function | PIK3CA act mut indicates that this variant results in a gain of function in the Pik3ca protein. However, the specific amino acid change has not been identified. | |
| amp | none | no effect | PIK3CA amplification indicates an increased number of copies of the PIK3CA gene. However, the mechanism causing the increase is unspecified. | |
| C24Y | missense | no effect - predicted | PIK3CA C24Y lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). C24Y results in cell proliferation and viability levels similar to wild-type Pik3ca in culture (PMID: 29533785), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| C378F | missense | unknown | PIK3CA C378F lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). C378F has been identified in the scientific literature (PMID: 34842356), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| C378R | missense | gain of function | PIK3CA C378R lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). C378R results in constitutive activation of Pi3k and Akt signaling, and decreased apoptosis in cell culture (PMID: 17363507). | |
| C378Y | missense | unknown | PIK3CA C378Y lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). C378Y results in increased transformation ability in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown. | |
| C407F | missense | unknown | PIK3CA C407F lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). C407F has been identified in sequencing studies (PMID: 30337457, PMID: 29386312), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| C407W | missense | unknown | PIK3CA C407W lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). C407W has been identified in sequencing studies (PMID: 26919320, PMID: 20826764, PMID: 25850943), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| C407Y | missense | unknown | PIK3CA C407Y lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). C407Y has been identified in sequencing studies (PMID: 27302833, PMID: 21984976), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| C420G | missense | unknown | PIK3CA C420G lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). The functional effect of C420G is conflicting, as it results in increased Akt phosphorylation and cell proliferation, and is transforming in cell culture in one study (PMID: 18074223), however in another study, induces similar cell proliferation and cell viability compared to wild-type Pik3ca, in two different cell lines (PMID: 29533785), and therefore, its effect on Pik3ca protein function is unknown. | |
| C420R | missense | gain of function | PIK3CA C420R lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). C420R confers a gain of function on Pik3ca, as indicated by constitutive phosphorylation of downstream targets Akt and S6, increased cell proliferation and migration, and is transforming in cell culture (PMID: 17376864, PMID: 29533785, PMID: 34779417). | |
| C604R | missense | gain of function | PIK3CA C604R lies within the PIK helical domain of the Pik3ca protein (UniProt.org). C604R results in increased cell proliferation, migration, and Akt phosphorylation compared to wild-type Pik3ca (PMID: 34779417) and increased transformation ability in several different cell lines in culture (PMID: 29533785, PMID: 34779417). | |
| C692Ffs*8 | frameshift | unknown | PIK3CA C692Ffs*8 indicates a shift in the reading frame starting at amino acid 692 and terminating 8 residues downstream causing a premature truncation of the 1068 amino acid Pik3ca protein (UniProt.org). C692Ffs*8 has been identified in the scientific literature (PMID: 34210658), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| C901F | missense | gain of function - predicted | PIK3CA C901F lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). C901F results in increased cell proliferation and migration (PMID: 34779417) and transformation ability in several different cell lines in culture (PMID: 29533785, PMID: 34779417), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| C901Y | missense | unknown | PIK3CA C901Y lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). C901Y has been identified in sequencing studies (PMID: 30268455, PMID: 28539465), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| C905S | missense | unknown | PIK3CA C905S lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). C905S results in increased levels of cell migration but similar levels of cell proliferation and phosphorylation of Akt to wild-type Pik3ca and is not transforming in culture (PMID: 34779417), and therefore, its effect on Pik3ca protein function is unknown. | |
| C90G | missense | unknown | PIK3CA C90G lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). C90G has been identified in sequencing studies (PMID: 31202631, PMID: 28528867), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| C90R | missense | unknown | PIK3CA C90R lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). C90R has been identified in sequencing studies (PMID: 28528867), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| C90S | missense | unknown | PIK3CA C90S lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). C90S has been identified in sequencing studies (PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| C90Y | missense | unknown | PIK3CA C90Y lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). C90Y has been identified in sequencing studies (PMID: 28528867, PMID: 30393068), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| C971R | missense | gain of function - predicted | PIK3CA C971R lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). C971R leads to Akt phosphorylation similar to wild-type Pik3ca (PMID: 34779417), but results in increased cell proliferation, viability, migration, and transformation ability compared to wild-type Pik3ca in several cell lines in culture (PMID: 29533785, PMID: 34779417), and in another study results in increased PI3K pathway signaling and moderate growth compared to control (PMID: 23619167), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| D1029H | missense | unknown | PIK3CA D1029H lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). D1029H has been identified in the scientific literature (PMID: 26643573, PMID: 22949056, PMID: 23718828), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| D1029Y | missense | gain of function | PIK3CA D1029Y lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). D1029Y confers a gain of function to the Pik3ca protein, as demonstrated by increased phosphorylation of Akt and transformation of cells in culture (PMID: 19394761). | |
| D1045N | missense | unknown | PIK3CA D1045N lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). D1045N has been identified in the scientific literature (PMID: 25624430, PMID: 26850916, PMID: 36698189), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| D1045V | missense | unknown | PIK3CA D1045V lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). D1045V has been identified in sequencing studies (PMID: 28936923), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| D1056G | missense | unknown | PIK3CA D1056G does not lie within any known functional domains of the Pik3ca protein (UniProt.org). D1056G has been identified in the scientific literature (PMID: 17317825), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| D300Y | missense | unknown | PIK3CA D300Y does not lie within any known functional domains of the Pik3ca protein (UniProt.org). D300Y has been identified in sequencing studies (PMID: 21984976), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| D350G | missense | gain of function | PIK3CA D350G lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). D350G results in increased phosphorylation of Akt in cell culture (PMID: 24265155) and demonstrates increased transformation ability in two different cell lines, as compared to wild-type Pik3ca (PMID: 29533785). | |
| D350H | missense | unknown | PIK3CA D350H lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). D350H has been identified in the scientific literature (PMID: 37318638, PMID: 28912153, PMID: 33203919), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| D350N | missense | gain of function - predicted | PIK3CA D350N lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). D350N results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| D350V | missense | unknown | PIK3CA D350V lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). D350V has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| D454Y | missense | unknown | PIK3CA D454Y lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). D454Y has been identified in sequencing studies (PMID: 26080840), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| D520V | missense | unknown | PIK3CA D520V lies within the PIK helical domain of the Pik3ca protein (UniProt.org). D520V has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| D538Y | missense | no effect - predicted | PIK3CA D538Y lies within the PIK helical domain of the Pik3ca protein (UniProt.org). D538Y results in cell growth levels similar to wild-type Pik3ca in culture (PMID: 29636477), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| D549H | missense | unknown | PIK3CA D549H lies within the PIK helical domain of the Pik3ca protein (UniProt.org). D549H has been identified in the scientific literature (PMID: 29106415, PMID: 30619505, PMID: 26080840), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| D549N | missense | gain of function - predicted | PIK3CA D549N lies within the PIK helical domain of the Pik3ca protein (UniProt.org). D549N results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| D549Y | missense | unknown | PIK3CA D549Y lies within the PIK helical domain of the Pik3ca protein (UniProt.org). D549Y has been identified in the scientific literature (PMID: 29106415, PMID: 26270481), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| D746V | missense | unknown | PIK3CA D746V does not lie within any known functional domains of the Pik3ca protein (UniProt.org). D746V has been identified in sequencing studies (PMID: 22653804), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| D926N | missense | unknown | PIK3CA D926N lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). D926N has been identified in sequencing studies (PMID: 30766968, PMID: 26099045), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| D939G | missense | gain of function - predicted | PIK3CA D939G lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). D939G results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| dec exp | none | no effect | PIK3CA dec exp indicates decreased expression of the Pik3ca protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified. | |
| E1037K | missense | gain of function - predicted | PIK3CA E1037K lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). E1037K results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E103_G106delinsD | indel | gain of function - predicted | PIK3CA E103_G106delinsD results in a deletion of four amino acids in the PI3K-ABD domain of the Pik3ca protein from amino acid 103 to 106, combined with the insertion of an aspartic acid (D) at the same site (UniProt.org). E103_G106delinsD results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E103_P104del | deletion | gain of function - predicted | PIK3CA E103_P104del results in the deletion of two amino acids in the PI3K-ABD domain of the Pik3ca protein from amino acids 103 to 104 (UniProt.org). E103_P104del results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E109_I112delinsD | indel | gain of function - predicted | PIK3CA E109_I112delinsD results in a deletion of four amino acids from amino acid 109 to 112 of the Pik3ca protein, combined with the insertion of an aspartic acid (D) at the same site (UniProt.org). E109_I112delinsD results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E110del | deletion | gain of function - predicted | PIK3CA E110del results in the deletion of an amino acid in the Pik3ca protein at amino acid 110 (UniProt.org). E110del results in Akt phosphorylation similar to wild-type Pik3ca (PMID: 34779417), but leads to increased cell proliferation and migration (PMID: 34779417) and transformation ability in several different cell lines in culture (PMID: 29533785, PMID: 34779417), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E110K | missense | unknown | PIK3CA E110K does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E110K has been identified in the scientific literature (PMID: 23619167, PMID: 29535826, PMID: 24559118), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| E110_K111dup | duplication | unknown | PIK3CA E110_K111dup indicates the insertion of two duplicate amino acids, glutamic acid (E)-110 through lysine (K)-111, of the Pik3ca protein (UniProt.org). E110_K111dup has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| E116K | missense | no effect | PIK3CA E116K does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E116K phosphorylates Akt to similar level of wild-type Pik3ca and is not transforming in culture (PMID: 17376864). | |
| E149G | missense | no effect - predicted | PIK3CA E149G does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E149G results in cell proliferation and viability levels similar to wild-type Pik3ca in culture (PMID: 29533785), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| E172Q | missense | unknown | PIK3CA E172Q does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E172Q has been identified in sequencing studies (PMID: 37916958), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Jan 2024). | |
| E218K | missense | no effect - predicted | PIK3CA E218K lies within the PI3K-RBD domain of the Pik3ca protein (UniProt.org). E218K results in cell proliferation and viability levels similar to wild-type Pik3ca in culture (PMID: 29533785), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| E218Tfs*7 | frameshift | unknown | PIK3CA E218Tfs*7 indicates a shift in the reading frame starting at amino acid 218 and terminating 7 residues downstream causing a premature truncation of the 1068 amino acid Pik3ca protein (UniProt.org). E218Tfs*7 has been identified in sequencing studies (PMID: 34476097), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| E321D | missense | unknown | PIK3CA E321D does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E321D has been identified in the scientific literature (PMID: 32098826), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| E365K | missense | gain of function - predicted | PIK3CA E365K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E365K results in increased phosphorylation of downstream targets Akt, GSK3-beta, FoxO1, FoxO3a, and S6 in cell culture (PMID: 18829572, PMID: 21266528), and in one of two cell lines, increased cell proliferation and cell viability compared to wild-type Pik3ca in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E365V | missense | gain of function | PIK3CA E365V lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E365V results in increased cell proliferation, migration, and phosphorylation of Akt compared to wild-type Pik3ca, and is transforming in several different cell lines in culture (PMID: 29533785, PMID: 34779417). | |
| E39G | missense | unknown | PIK3CA E39G lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). E39G has been identified in sequencing studies (PMID: 28528867), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| E39K | missense | gain of function - predicted | PIK3CA E39K lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). E39K results in increased cell proliferation and transformation ability in culture (PMID: 29533785, PMID: 29636477), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E418K | missense | gain of function | PIK3CA E418K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E418K results in increased cell proliferation, migration, and increased phosphorylation of Akt compared to wild-type Pik3ca and is transforming in culture (PMID: 34779417). | |
| E453A | missense | gain of function | PIK3CA E453A lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E453A confers a gain of function to Pik3ca, as indicated by increased Akt phosphorylation in cell culture (PMID: 21266528) and increased transformation ability in two different cell lines, as compared to wild-type Pik3ca (PMID: 29533785). | |
| E453D | missense | unknown | PIK3CA E453D lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E453D has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| E453del | deletion | unknown | PIK3CA E453del results in the deletion of an amino acid in the C2 PI3K-type domain of the Pik3ca protein at amino acid 453 (UniProt.org). E453del has been identified in sequencing studies (PMID: 35145232, PMID: 31349857, PMID: 26226847), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| E453G | missense | unknown | PIK3CA E453G lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E453G has been identified in the scientific literature (PMID: 35768433), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| E453K | missense | gain of function | PIK3CA E453K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E453K results in increased phosphorylation of Akt and Mek1/2, enhanced cell survival, increased cell proliferation and migration, and is transforming in culture (PMID: 26627007, PMID: 29533785, PMID: 34779417). | |
| E453Q | missense | gain of function | PIK3CA E453Q lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E453Q confers a gain of function to Pik3ca as indicated by increased lipid kinase activity in cell culture (PMID: 15930273) and demonstrates increased transformation ability in two different cell lines, as compared to wild-type Pik3ca (PMID: 29533785). | |
| E453_D454del | deletion | unknown | PIK3CA E453_D454del results in the deletion of two amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 453 to 454 (UniProt.org). E453_D454del has been identified in sequencing studies (PMID: 30393068), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| E453_L455delinsV | indel | unknown | PIK3CA E453_L455delinsV results in the deletion of three amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 453 to 455, combined with the insertion of a valine (V) at the same site (UniProt.org). E453_L455delinsV has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Jan 2024). | |
| E453_P466del | deletion | unknown | PIK3CA E453_P466del results in the deletion of 14 amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 453 to 466 (UniProt.org). E453_P466del has been identified in sequencing studies (PMID: 30393068), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| E453_T462del | deletion | unknown | PIK3CA E453_T462del results in the deletion of ten amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 453 to 462 (UniProt.org). E453_T462del has been identified in sequencing studies (PMID: 30393068), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| E469delinsDK | indel | gain of function - predicted | PIK3CA E469delinsDK results in the deletion of a glutamic acid (E) at amino acid 469 within the C2 PI3K-type domain of the Pik3ca protein, combined with the insertion of an aspartic acid (D) and lysine (K) at the same site (UniProt.org). E469delinsDK results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E474D | missense | unknown | PIK3CA E474D lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E474D has been identified in the scientific literature (PMID: 36387265), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| E522A | missense | unknown | PIK3CA E522A lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E522A has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| E542A | missense | gain of function - predicted | PIK3CA E542A lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E542A results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E542G | missense | gain of function - predicted | PIK3CA E542G lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E542G results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E542K | missense | gain of function | PIK3CA E542K is a hotspot mutation that lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E542K results in increased phosphorylation of Akt, growth factor-independent cell survival, and is transforming in cell culture (PMID: 16533766, PMID: 26627007, PMID: 29533785). | |
| E542Q | missense | unknown | PIK3CA E542Q lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E542Q results in cell proliferation and cell viability similar to wild-type Pik3ca in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown. | |
| E542V | missense | gain of function | PIK3CA E542V is a hotspot mutation that lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E542V confers a gain of function on Pik3ca, as indicated by increased phosphorylation of Akt and Mek1/2, growth-factor independent cell survival, and is transforming in culture (PMID: 26627007, PMID: 29533785). | |
| E542X | missense | unknown | PIK3CA E542X indicates any Pik3ca missense mutation that results in the replacement of the glutamic acid (E) at amino acid 542 by a different amino acid. | |
| E545A | missense | gain of function | PIK3CA E545A is a hotspot mutation that lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E545A confers a gain of function on the Pik3ca protein as demonstrated by increased phosphorylation of Akt and transformation in cell culture (PMID: 17376864, PMID: 29533785). | |
| E545D | missense | gain of function - predicted | PIK3CA E545D is a hotspot mutation that lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E545D results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E545G | missense | gain of function | PIK3CA E545G is a hotspot mutation that lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E545G confers a gain of function on the Pik3ca protein as demonstrated by increased phosphorylation of Akt and transformation in cell culture (PMID: 17376864, PMID: 29533785). | |
| E545K | missense | gain of function | PIK3CA E545K is a hotspot mutation that lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E545K results in increased phosphorylation of Akt and Mek1/2, growth factor-independent cell survival, and is transforming in culture (PMID: 26627007, PMID: 29533785). | |
| E545Q | missense | gain of function - predicted | PIK3CA E545Q is a hotspot mutation that lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E545Q results in growth factor-independent cell survival and transformation in culture (PMID: 26627007, PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E545V | missense | unknown | PIK3CA E545V is a hotspot mutation that lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E545V has been identified in sequencing studies (PMID: 29482551, PMID: 24504419), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| E545X | missense | unknown | PIK3CA E545X indicates any Pik3ca missense mutation that results in the replacement of the glutamic acid (E) at amino acid 545 by a different amino acid. PIK3CA E545X mutations are hotspot mutations that may result in increased Pik3ca kinase activity (PMID: 15930273). | |
| E547K | missense | unknown | PIK3CA E547K is a hotspot mutation that lies within the PIK helical domain of the Pik3ca protein (PMID: 27177864). E547K results in decreased cell viability compared to wild-type Pik3ca in one of two cell lines in culture (PMID: 29533785), but has not been biochemically characterized, and therefore, its effect on Pik3ca protein function is unknown. | |
| E563K | missense | unknown | PIK3CA E563K lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E563K has been identified in the scientific literature (PMID: 32923889), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| E600K | missense | unknown | PIK3CA E600K lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E600K has been identified in the scientific literature (PMID: 35709927, PMID: 35977725), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| E674Q | missense | unknown | PIK3CA E674Q lies within the PIK helical domain of the Pik3ca protein (UniProt.org). E674Q has been identified in the scientific literature (PMID: 25349966, PMID: 28760909), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| E710G | missense | no effect - predicted | PIK3CA E710G does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E710G results in cell growth levels similar to wild-type Pik3ca in culture (PMID: 29636477), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| E722K | missense | unknown | PIK3CA E722K does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E722K has been identified in the scientific literature (PMID: 31852484, PMID: 35768433), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| E726A | missense | unknown | PIK3CA E726A does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E726A has been identified in sequencing studies (PMID: 24705251, PMID: 32650224), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Jan 2024). | |
| E726G | missense | unknown | PIK3CA E726G does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E726G has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Apr 2024). | |
| E726K | missense | gain of function | PIK3CA E726K does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E726K results in increased cell proliferation and migration and increased Akt phosphorylation compared to wild-type Pik3ca in culture (PMID: 34779417) and increased transformation ability in several different cell lines in culture (PMID: 29533785, PMID: 34779417). | |
| E726Q | missense | unknown | PIK3CA E726Q does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E726Q has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| E737Q | missense | unknown | PIK3CA E737Q does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E737Q has been identified in sequencing studies (PMID: 37916958), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Jan 2024). | |
| E78K | missense | unknown | PIK3CA E78K lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). E78K has been identified in the scientific literature (PMID: 27126994), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| E80K | missense | unknown | PIK3CA E80K lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). E80K has been identified in the scientific literature (PMID: 29636477, PMID: 22722201, PMID: 31174159), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| E81* | nonsense | loss of function - predicted | PIK3CA E81* results in a premature truncation of the Pik3ca protein at amino acid 81 of 1068 (UniProt.org). Due to the loss of PI3K/PI4K kinase domain (UniProt.org), E81* is predicted to lead to a loss of Pik3ca protein function. | |
| E81K | missense | unknown | PIK3CA E81K lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). The functional effect of E81K is conflicting, as it results in cell proliferation, migration, and Akt phosphorylation similar to wild-type Pik3ca in culture and is not transforming in one study (PMID: 34779417), but in other studies it leads to decreased cell proliferation and cell viability (PMID: 29533785) and increased Akt phosphorylation, activation of Mtor signaling, and growth advantage in patient-derived dermal fibroblasts in culture (PMID: 25915946), and therefore, its effect on Pik3ca protein function is unknown. | |
| E970K | missense | gain of function - predicted | PIK3CA E970K lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). E970K results in phosphorylated Akt levels similar to wild-type Pik3ca, but increased proliferation and cell migration and is transforming in culture (PMID: 34779417), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| E978K | missense | unknown | PIK3CA E978K lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). E978K has been identified in the scientific literature (PMID: 28119489), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| exon10 | unknown | unknown | PIK3CA exon 10 indicates an unspecified mutation has occurred in exon 10 (corresponding to amino acids 514 to 555) of the PIK3CA gene. PIK3CA exon 10 is sometimes reported as exon 9, when only coding exons are considered in numbering. | |
| exon20 | unknown | unknown | PIK3CA exon 20 indicates an unspecified mutation has occurred in exon 20 (corresponding to amino acids 929 to 979) of the PIK3CA gene. PIK3CA exon 21 (corresponding to amino acids 979 to 1068) is sometimes reported as exon 20, when only coding exons are considered in numbering. | |
| exon21 | unknown | unknown | PIK3CA exon 21 indicates an unspecified mutation has occurred in exon 21 (corresponding to amino acids 979 to 1068) of the PIK3CA gene. PIK3CA exon 21 is sometimes reported as exon 20, when only coding exons are considered in numbering. | |
| exon5 | unknown | unknown | PIK3CA exon 5 indicates an unspecified mutation has occurred in exon 5 (corresponding to amino acids 272 to 353) of the PIK3CA gene. PIK3CA exon 5 is sometimes reported as exon 4, when only coding exons are considered in numbering. | |
| exon8 | unknown | unknown | PIK3CA exon 8 indicates an unspecified mutation has occurred in exon 8 (corresponding to amino acids 418 to 468) of the PIK3CA gene. PIK3CA exon 8 is sometimes reported as exon 7, when only coding exons are considered in numbering. | |
| exon9 | unknown | unknown | PIK3CA exon 9 indicates an unspecified mutation has occurred in exon 9 (corresponding to amino acids 469 to 513) of the PIK3CA gene. PIK3CA exon 10 (corresponding to amino acids 514 to 555) is sometimes reported as exon 9, when only coding exons are considered in numbering. | |
| F1039L | missense | unknown | PIK3CA F1039L lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). F1039L has been identified in sequencing studies (PMID: 30089603, PMID: 22949056, PMID: 19487299), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| F550S | missense | unknown | PIK3CA F550S lies within the PIK helical domain of the Pik3ca protein (UniProt.org). F550S has been identified in sequencing studies (PMID: 30268455, PMID: 19487299, PMID: 17317825), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| F614I | missense | no effect - predicted | PIK3CA F614I lies within the PIK helical domain of the Pik3ca protein (UniProt.org). F614I results in cell proliferation and viability levels similar to wild-type Pik3ca in culture (PMID: 29533785), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| F744L | missense | unknown | PIK3CA F744L does not lie within any known functional domains of the Pik3ca protein (UniProt.org). F744L has been identified in the scientific literature (PMID: 30683736), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| F909L | missense | unknown | PIK3CA F909L lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). F909L has been identified in sequencing studies (PMID: 24440717, PMID: 15805248), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| F930S | missense | gain of function - predicted | PIK3CA F930S lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). F930S results in activation of Pik3ca signaling as indicated by increased phosphorylation of Akt and Mapk3/Mapk1 (Erk1/2), and confers resistance to some EGFR inhibitors in culture (PMID: 28424201), and therefore, is predicted to lead to a gain of Pik3ca protein function. | Y |
| F977Y | missense | unknown | PIK3CA F977Y lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). F977Y has been associated with resistance to a PI3K inhibitor in culture (PMID: 30108165), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | Y |
| G1007D | missense | unknown | PIK3CA G1007D lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). G1007D has been identified in the scientific literature (PMID: 16288007), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| G1007R | missense | gain of function | PIK3CA G1007R lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). G1007R results in increased cell proliferation and migration and increased Akt phosphorylation compared to wild-type Pik3ca in culture (PMID: 34779417) and increased transformation ability in several different cell lines in culture (PMID: 29533785, PMID: 34779417). | |
| G1009R | missense | unknown | PIK3CA G1009R lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). G1009R has been identified in sequencing studies (PMID: 34150029), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| G1049A | missense | unknown | PIK3CA G1049A lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). G1049A has been identified in the scientific literature (PMID: 34249978, PMID: 35355608), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| G1049C | missense | unknown | PIK3CA G1049C lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). G1049C has been identified in sequencing studies (PMID: 29854313, PMID: 23266353), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| G1049D | missense | unknown | PIK3CA G1049D lies within the PI3K/PI4K protein kinase domain of the Pik3ca protein (UniProt.org). G1049D has been identified in the scientific literature (PMID: 28731042, PMID: 26452060, PMID: 24062397), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| G1049R | missense | gain of function | PIK3CA G1049R lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). G1049R results in increased phosphorylation of Akt and Mek1/2, growth factor-independent cell survival, and transforming in cell culture (PMID: 26627007, PMID: 29533785). | |
| G1049S | missense | unknown | PIK3CA G1049S lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). G1049S has been identified in the scientific literature (PMID: 17052259, PMID: 25656989, PMID: 27177864), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| G106C | missense | unknown | PIK3CA G106C does not lie within any known functional domains of the Pik3ca protein (UniProt.org). G106C has been identified in sequencing studies (PMID: 31312661), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| G106R | missense | gain of function - predicted | PIK3CA G106R does not lie within any known functional domains of the Pik3ca protein (UniProt.org). G106R results in increased Akt phosphorylation in cell culture (PMID: 21266528), and in one of two cell lines, leads to increased cell proliferation and cell viability compared to wild-type Pik3ca in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| G106S | missense | unknown | PIK3CA G106S does not lie within any known functional domains of the Pik3ca protein (UniProt.org). G106S has been identified in sequencing studies (PMID: 28500398, PMID: 23700467, PMID: 28528867), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Jan 2024). | |
| G106V | missense | gain of function | PIK3CA G106V does not lie within any known functional domains of the Pik3ca proten (UniProt.org). G106V results in activation of Pik3ca as indicated by increased Akt phosphorylation in cell culture (PMID: 21266528), increased cell invasion and migration in the context of an EGFR activating mutation in vitro (PMID: 29106415), and increased transformation ability in two different cell lines (PMID: 29533785). | |
| G106_N107del | deletion | unknown | PIK3CA G106_N107del results in the deletion of two amino acids of the Pik3ca protein from amino acids 106 to 107 (UniProt.org). G106_N107del has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| G106_R108del | deletion | gain of function | PIK3CA G106_R108del results in the deletion of three amino acids in the region linking the PI3K-ABD and PI3K-RBD domains of the Pik3ca protein from amino acids 106 to 108 (UniProt.org). G106_R108del results in increased phosphorylation of Akt and is transforming in cell culture (PMID: 19394761, PMID: 29533785). | |
| G118D | missense | gain of function | PIK3CA G118D lies within the region linking the PI3K-ABD and PI3K-RBD domains of the Pik3ca protein (UniProt.org). G118D confers a gain of function on the Pik3ca protein as indicated by enhanced lipid kinase activity in cell culture, increased phosphorylation of Akt in cells derived from Cowden syndrome patients harboring germline mutations (PMID: 22949682, PMID: 23246288), and increased transformation ability in two different cell lines (PMID: 29533785). | |
| G12D | missense | unknown | PIK3CA G12D does not lie within any known functional domains of the Pik3ca protein (UniProt.org). G12D has been identified in sequencing studies (PMID: 23933559, PMID: 32947236), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| G363A | missense | unknown | PIK3CA G363A lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). The functional effect of G363A is conflicting, as it demonstrates increased PI3K pathway signaling and moderate growth in culture (PMID: 23619167, PMID: 28528867) and increased cell migration (PMID: 34779417), however in other studies, results in cell proliferation levels, cell viability, and Akt phosphorylation similar to wild-type Pik3ca (PMID: 29533785, PMID: 34779417) and is not transforming in culture (PMID: 34779417), and therefore, its effect on Pik3ca protein function is unknown. | |
| G364A | missense | unknown | PIK3CA G364A lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). G364A has been identified in sequencing studies (PMID: 30393068), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| G364R | missense | gain of function | PIK3CA G364R lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). G364R results in increased phosphorylation of Akt in cell culture (PMID: 21266528) and demonstrates increased transformation ability in two different cell lines, as compared to wild-type Pik3ca (PMID: 29533785). | |
| G451R | missense | gain of function | PIK3CA G451R lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). G451R results in increased cell proliferation and migration and increased Akt phosphorylation compared to wild-type Pik3ca in culture (PMID: 34779417) and increased transformation ability in several different cell lines in culture (PMID: 29533785, PMID: 34779417). | |
| G451V | missense | unknown | PIK3CA G451V lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). G451V results in increased cell proliferation and cell viability compared to wild-type Pik3ca in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown. | |
| G451_D454del | deletion | unknown | PIK3CA G451_D454del results in the deletion of four amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 451 to 454 (UniProt.org). G451_D454del has been identified in sequencing studies (PMID: 26587011), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| G463_N465del | deletion | unknown | PIK3CA G463_N465del results in the deletion of three amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 463 to 465 (UniProt.org). G463_N465del has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| G463_N465delinsD | indel | unknown | PIK3CA G463_N465delinsD results in the deletion of three amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 463 to 465, combined with the insertion of an aspartic acid (D) at the same site (UniProt.org). G463_N465delinsD has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| G512* | nonsense | loss of function - predicted | PIK3CA G512* results in a premature truncation of the Pik3ca protein at amino acid 512 of 1068 (UniProt.org). Due to the loss of the PI3K/PI4K kinase domain (UniProt.org), G512* is predicted to lead to a loss of Pik3ca protein function. | |
| G914R | missense | unknown | PIK3CA G914R lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). G914R has been identified in sequencing studies (PMID: 30709910, PMID: 26080840), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| H1047K | missense | unknown | PIK3CA H1047K is a hotspot mutation that lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). H1047K has been identified in the scientific literature (PMID: 27374081, PMID: 26783290, PMID: 34159748), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| H1047L | missense | gain of function | PIK3CA H1047L is a hotspot mutation that lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). H1047L results in increased phosphorylation of Akt and Mek1/2, growth factor-independent cell survival, and transformation in cell culture (PMID: 26627007, PMID: 29533785). | |
| H1047P | missense | unknown | PIK3CA H1047P is a hotspot mutation that lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). H1047P has been identified in sequencing studies (PMID: 22357840), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| H1047Q | missense | unknown | PIK3CA H1047Q is a hotspot mutation that lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). H1047Q has been identified in sequencing studies (PMID: 31158500, PMID: 30547809, PMID: 35880223), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| H1047R | missense | gain of function | PIK3CA H1047R is a hotspot mutation that lies within the kinase domain of the Pik3ca protein (UniProt.org). H1047R results in increased phosphorylation of Akt and Mek1/2, growth factor-independent cell survival, and transformation in cell culture (PMID: 26627007, PMID: 29533785). | |
| H1047T | missense | unknown | PIK3CA H1047T is a hotspot mutation that lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). H1047T has identified in the scientific literature (PMID: 29636477), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| H1047X | missense | unknown | PIK3CA H1047X indicates any Pik3ca missense mutation that results in the replacement of the histidine (H) at amino acid 1047 by a different amino acid. PIK3CA H1047X mutations are hotspot mutations that may result in increased Pik3ca kinase activity and cell transformation in culture (PMID: 15930273). | |
| H1047Y | missense | gain of function | PIK3CA H1047Y is a hotspot mutation that lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). H1047Y confers a gain of function on the Pik3ca protein as indicated by increased phosphorylation of Akt, activation of downstream signaling, and is transforming in cell culture (PMID: 17376864, PMID: 29533785). | |
| H1048L | missense | unknown | PIK3CA H1048L lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). H1048L has been identified in the scientific literature (PMID: 32042320), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| H1048R | missense | unknown | PIK3CA H1048R lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). H1048R has been identified in the scientific literature (PMID: 35639393, PMID: 30181556, PMID: 28638113), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| H1065L | missense | unknown | PIK3CA H1065L does not lie within any known functional domain of the Pik3ca protein (UniProt.org). H1065L has been identified in the scientific literature (PMID: 29515801, PMID: 27334835, PMID: 18084252), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| H1065Y | missense | unknown | PIK3CA H1065Y does not lie within any known functional domains of the Pik3ca protein (UniProt.org). H1065Y has been identified in sequencing studies (PMID: 15289301, PMID: 30503610, PMID: 33868589), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| H419_C420del | deletion | unknown | PIK3CA H419_C420del results in the deletion of two amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 419 to 420 (UniProt.org). H419_C420del has been identified in sequencing studies (PMID: 30212483, PMID: 26051240, PMID: 26080840), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Jan 2024). | |
| H419_L422del | deletion | unknown | PIK3CA H419_L422del results in the deletion of four amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 419 to 422 (UniProt.org). H419_L422del has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| H450_L455del | deletion | unknown | PIK3CA H450_L455del results in the deletion of six amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 450 to 455 (UniProt.org). H450_L455del has been identified in sequencing studies (PMID: 30393068), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| H450_P458del | deletion | gain of function | PIK3CA H450_P458del results in the deletion of nine amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 450 to 458 (UniProt.org). H450_P458del confers a gain of function to the Pik3ca protein as demonstrated by transformation in culture and activation of the PI3K/Akt/Mtor pathway via increased phosphorylation of Akt, Erk, P70S6K, and P90RSK (PMID: 29284706). | |
| H47R | missense | unknown | PIK3CA H47R lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). H47R has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| H665Q | missense | unknown | PIK3CA H665Q lies within the PIK helical domain of the Pik3ca protein (UniProt.org). H665Q has been identified in sequencing studies (PMID: 23028188), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| H701P | missense | no effect | PIK3CA H701P does not lie within any known functional domains of the Pik3ca protein (UniProt.org). H701P demonstrates transformation potential and ability to promote growth factor-independent cell survival at similar levels to wild-type Pik3ca protein in cell culture (PMID: 26627007, PMID: 29533785). | |
| H701R | missense | unknown | PIK3CA H701R does not lie within any known functional domains of the Pik3ca protein (UniProt.org). H701R has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| I102del | deletion | unknown | PIK3CA I102del results in the deletion of an amino acid in the PI3K-ABD domain of the Pik3ca protein (UniProt.org). I102del has been identified in sequencing studies (PMID: 26722235, PMID: 28528867), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| I102_E103delinsK | indel | unknown | PIK3CA I102_E103delinsK results in a deletion of two amino acids in the PI3K-ABD domain of the Pik3ca protein from amino acids 102 to 103, combined with the insertion of a lysine (K) at the same site (UniProt.org). I102_E103delinsK has been identified in sequencing studies (PMID: 30393068, PMID: 33083132), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| I1058F | missense | unknown | PIK3CA I1058F does not lie within any known functional domains of the Pik3ca protein (UniProt.org). I1058F has been identified in sequencing studies (PMID: 17062663, PMID: 21266528, PMID: 32958578), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| I1058L | missense | unknown | PIK3CA I1058L does not lie within any known functional domains of the Pik3ca protein (UniProt.org). I1058L has been identified in sequencing studies (PMID: 32958578), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| I112N | missense | unknown | PIK3CA I112N does not lie within any known functional domains of the Pik3ca protein (UniProt.org). I112N demonstrates increased transformation ability in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown. | |
| I112_L113del | deletion | unknown | PIK3CA I112_L113del results in the deletion of two amino acids of the Pik3ca protein from amino acids 112 to 113 (UniProt.org). I112_L113del has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| I197K | missense | unknown | PIK3CA I197K lies within the PI3K-RBD domain of the Pik3ca protein (UniProt.org). I197K has been identified in sequencing studies (PMID: 37916958), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Jan 2024). | |
| I20M | missense | unknown | PIK3CA I20M lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). I20M has been identified in the scientific literature (PMID: 29426295, PMID: 28119489), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| I273V | missense | unknown | PIK3CA I273V lies within the PI3K-RBD domain of the Pik3ca protein (UniProt.org). I273V has been identified in the scientific literature (PMID: 27126994), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| I31M | missense | no effect | PIK3CA I31M lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). I31M demonstrates transformation potential and ability to promote growth factor-independent cell survival at similar levels to wild-type Pik3ca protein in cell culture (PMID: 26627007, PMID: 29533785 ). | |
| I391M | missense | unknown | PIK3CA I391M lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). I391M demonstrates kinase activity similar to wild-type Pik3ca in one study (PMID: 20530683), but results in increased cell proliferation and cell viability as compared to wild-type Pik3ca in one of two different cell lines (PMID: 29533785), and therefore, its effect on Pik3ca protein function is unknown. | |
| I406V | missense | unknown | PIK3CA I406V lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). I406V has been identified in sequencing studies (PMID: 23028188, PMID: 21984976), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| I43M | missense | unknown | PIK3CA I43M lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). I43M has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| I459_T462del | deletion | gain of function - predicted | PIK3CA I459_T462del results in the deletion of four amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 459 to 462 (UniProt.org). PIK3CA I459_T462del results in increased phosphorylation of Akt, Erk, P70S6K, and S6 in culture (PMID: 35012940), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| I817F | missense | unknown | PIK3CA I817F lies within the PI3K/PI4K catalytic domain of the Pik3ca protein (UniProt.org). I817F has been identified in the scientific literature (PMID: 37916958), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| I889M | missense | unknown | PIK3CA I889M lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). I889M has been identified in sequencing studies (PMID: 29212173, PMID: 22975805), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| I910M | missense | unknown | PIK3CA I910M lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). I910M has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| I910V | missense | unknown | PIK3CA I910V lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). I910V results in increased cell proliferation and cell viability compared to wild-type Pik3ca in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown. | |
| inact mut | unknown | loss of function | PIK3CA inact mut indicates that this variant results in a loss of function of the Pik3ca protein. However, the specific amino acid change has not been identified. | |
| K111del | deletion | gain of function - predicted | PIK3CA K111del results in the deletion of an amino acid in the Pik3ca protein at amino acid 111 (UniProt.org). K111del results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| K111E | missense | gain of function | PIK3CA K111E lies within the region linking the PI3K-ABD and PI3K-RBD domains of the Pik3ca protein (UniProt.org). K111E confers a gain of function on the Pik3ca protein as indicated by increased lipid kinase activity and phosphorylation of Akt in cell culture (PMID: 22949682, PMID: 21266528), increased cell proliferation and migration, and is transforming in culture (PMID: 29533785, PMID: 34779417). | |
| K111N | missense | gain of function | PIK3CA K111N lies within the region linking the PI3K-ABD and PI3K-RBD domains of the Pik3ca protein (UniProt.org). K111N results in increased phosphorylation of Akt, activation of downstream signaling, increased cell proliferation and migration, and is transforming in cell culture (PMID: 17376864, PMID: 29533785, PMID: 34779417). | |
| K111Q | missense | unknown | PIK3CA K111Q does not lie within any known functional domains of the Pik3ca protein (UniProt.org). K111Q has been identified in sequencing studies (PMID: 30393068, PMID: 36800542), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| K111R | missense | unknown | PIK3CA K111R does not lie within any known functional domains of the Pik3ca protein (UniProt.org). K111R has been identified in sequencing studies (PMID: 28027320, PMID: 27641744, PMID: 23917401), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| K111_I112del | deletion | unknown | PIK3CA K111_I112del results in the deletion of two amino acids of the Pik3ca protein from amino acids 111 to 112 (UniProt.org). K111_I112del has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| K179T | missense | unknown | PIK3CA K179T does not lie within any known functional domains of the Pik3ca protein (UniProt.org). K179T has been identified in sequencing studies (PMID: 18224685), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| K51N | missense | no effect - predicted | PIK3CA K51N lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). K51N results in cell growth levels similar to wild-type Pik3ca in culture (PMID: 29636477), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| K567R | missense | unknown | PIK3CA K567R lies within the PIK helical domain of the Pik3ca protein (UniProt.org). K567R has been identified in the scientific literature (PMID: 17314276), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| K944N | missense | gain of function - predicted | PIK3CA K944N lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). K944N results in activation of Pik3ca signaling as indicated by increased phosphorylation of Akt and Mapk3/Mapk1 (Erk1/2), and confers resistance to some EGFR inhibitors in cell culture (PMID: 28424201) and therefore, is predicted to lead to a gain of Pik3ca protein function. | Y |
| K966E | missense | gain of function - predicted | PIK3CA K966E lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). K966E results in activation of Pik3ca signaling as indicated by increased phosphorylation of Akt and Mapk3/Mapk1 (Erk1/2), and confers resistance to some EGFR inhibitors in cell culture (PMID: 28424201), and therefore, is predicted to lead to a gain of Pik3ca protein function. | Y |
| L1001P | missense | unknown | PIK3CA L1001P lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). L1001P has been identified in the scientific literature (PMID: 27369867), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| L10_M16del | deletion | unknown | PIK3CA L10_M16del results in the deletion of seven amino acids of the Pik3ca protein from amino acids 10 to 16 (UniProt.org). L10_M16del has been identified in the scientific literature (PMID: 28528867, PMID: 23708221), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| L10_P18del | deletion | unknown | PIK3CA L10_P18del results in the deletion of nine amino acids of the Pik3ca protein from amino acids 10 to 18 (UniProt.org). L10_P18del has been identified in the scientific literature (PMID: 35917491), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| L113del | deletion | unknown | PIK3CA L113del results in the deletion of an amino acid of the Pik3ca protein at amino acid 113 (UniProt.org). L113del has been identified in sequencing studies (PMID: 30138724, PMID: 31980592), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| L339I | missense | unknown | PIK3CA L339I lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). L339I has been identified in the scientific literature (PMID: 25078343, PMID: 28978093, PMID: 28027320), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| L436_P449dup | duplication | unknown | PIK3CA L436_P449dup indicates the insertion of 14 duplicate amino acids, leucine (L)-436 through proline (P)-449, in the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). L436_P449dup has been identified in sequencing studies (PMID: 30393068), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| L452_G460del | deletion | unknown | PIK3CA L452_G460del results in the deletion of nine amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 452 to 460 (UniProt.org). L452_G460del has been identified in the scientific literature (PMID: 28528867), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| L452_P458del | deletion | unknown | PIK3CA L452_P458del results in the deletion of seven amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 452 to 458 (UniProt.org). L452_P458del has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| L455_G460delinsF | indel | unknown | PIK3CA L455_G460delinsF results in a deletion of six amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 455 to 460, combined with the insertion of a phenylalanine (F) at the same site (UniProt.org). L455_G460delinsF has been identified in sequencing studies (PMID: 35242279), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| L456Afs*13 | frameshift | unknown | PIK3CA L456Afs*13 indicates a shift in the reading frame starting at amino acid 456 and terminating 13 residues downstream causing a premature truncation of the 1068 amino acid Pik3ca protein (UniProt.org). L456Afs*13 results in decreased transformation ability in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown. | |
| L456R | missense | unknown | PIK3CA L456R lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). L456R has been identified in sequencing studies (PMID: 25528496, PMID: 30503610), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| L766F | missense | no effect - predicted | PIK3CA L766F lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). L766F results in similar levels of cell proliferation and viability to wild-type Pik3ca (PMID: 29533785) and therefore, is predicted to have no effect on Pik3ca protein function. | |
| L866F | missense | unknown | PIK3CA L866F lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). L866F has been identified in sequencing studies (PMID: 18772396), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| L938* | nonsense | gain of function - predicted | PIK3CA L938* results in a premature truncation of the Pik3ca protein at amino acid 938 of 1068 (UniProt.org). L938* results in activation of Pik3ca signaling as indicated by increased phosphorylation of Akt and Mapk3/Mapk1 (Erk1/2) in cell culture (PMID: 28424201), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| M1004I | missense | unknown | PIK3CA M1004I lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). M1004I results in increased cell proliferation and cell viability compared to wild-type Pik3ca in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown. | |
| M1004R | missense | unknown | PIK3CA M1004R lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). M1004R has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Jan 2024). | |
| M1004V | missense | unknown | PIK3CA M1004V lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). M1004V has been identified in the scientific literature (PMID: 32123305), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Jan 2024). | |
| M1040I | missense | no effect | PIK3CA M1040I lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). M1040I results in evels of cell proliferation, migration, and phosphorylation of Akt similar to wild-type Pik3ca and is not transforming in culture (PMID: 34779417). | |
| M1040V | missense | no effect - predicted | PIK3CA M1040V lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). M1040V results in similar levels of cell proliferation and viability to wild-type Pik3ca in culture (PMID: 29533785), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| M1043I | missense | gain of function | PIK3CA M1043I lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). M1043I confers a gain of function on the Pik3ca protein as indicated by in increased phosphorylation of Akt, activation of downstream signaling, and transformation in cell culture (PMID: 17376864, PMID: 29533785). | |
| M1043L | missense | gain of function - predicted | PIK3CA M1043L lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). M1043L results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| M1043T | missense | unknown | PIK3CA M1043T lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). M1043T has been identified in sequencing studies (PMID: 28830922, PMID: 25528496, PMID: 23370426), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| M1043V | missense | gain of function | PIK3CA M1043V lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). M1043V results in increased phosphorylation of Akt, activation of downstream signaling, increased cell proliferation and migration, and is transforming in cell culture (PMID: 17376864, PMID: 29533785, PMID: 34779417). | |
| mutant | unknown | unknown | PIK3CA mutant indicates an unspecified mutation within the PIK3CA gene. | |
| N1000D | missense | unknown | PIK3CA N1000D lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). N1000D has been identified in the scientific literature (PMID: 22949056, PMID: 24983367), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| N1044D | missense | unknown | PIK3CA N1044D lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). N1044D has been identified in the scientific literature (PMID: 27468883, PMID: 34287479, PMID: 18180098), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| N1044I | missense | unknown | PIK3CA N1044I lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). N1044I has been identified in sequencing studies (PMID: 28528867), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| N1044K | missense | gain of function | PIK3CA N1044K lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). N1044K confers a gain of function to Pik3ca protein as indicated by increased cell survival and transforming ability in cell culture (PMID: 26627007, PMID: 29533785). | |
| N1044S | missense | unknown | PIK3CA N1044S lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). N1044S has been identified in the scientific literature (PMID: 26085511, PMID: 22653804, PMID: 32816889), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| N1044Y | missense | unknown | PIK3CA N1044Y lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). N1044Y has been identified in the scientific literature (PMID: 29636477, PMID: 27191687, PMID: 27548314), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| N1068Kfs*5 | frameshift | gain of function | PIK3CA N1068Kfs*5 indicates a shift in the reading frame starting at the final amino acid of the Pik3ca protein, 1068, and terminating 5 residues downstream, resulting in extension of the Pik3ca protein length by 3 amino acids (UniProt.org). N1068Kfs*5 results in increased cell proliferation, migration, and Akt phosphorylation compared to wild-type Pik3ca (PMID: 34779417), and increased transformation ability in several different cell lines in culture (PMID: 29533785, PMID: 34779417). | |
| N107I | missense | unknown | PIK3CA N107I does not lie within any known functional domains of the Pik3ca protein (UniProt.org). N107I has been identified in sequencing studies (PMID: 30393068), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| N107S | missense | unknown | PIK3CA N107S does not lie within any known functional domains of the Pik3ca protein (UniProt.org). N107S has been identified in the scientific literature (PMID: 32349306), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| N114del | deletion | unknown | PIK3CA N114del results in the deletion of an amino acid of the Pik3ca protein at amino acid 114 (UniProt.org). N114del has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| N170S | missense | unknown | PIK3CA N170S does not lie within any known functional domains of the Pik3ca protein (UniProt.org). N170S has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| N345D | missense | unknown | PIK3CA N345D lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N345D has been identified in the scientific literature (PMID: 30562681, PMID: 27034166, PMID: 36010918), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| N345H | missense | unknown | PIK3CA N345H lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N345H has been identified in the scientific literature (PMID: 25846456, PMID: 30181556, PMID: 26650777), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| N345I | missense | gain of function - predicted | PIK3CA N345I lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N345I results in increased cell survival, but was not transforming in cell culture in one study (PMID: 26627007), but in two other studies, demonstrated increased transformation ability in multiple cell lines compared to wild-type Pik3ca in culture (PMID: 29533785, PMID: 29636477), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| N345K | missense | gain of function | PIK3CA N345K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N345K results in increased phosphorylation of Akt, activation of downstream signaling, increased cell proliferation and migration, and is transforming in cell culture (PMID: 17376864, PMID: 29533785, PMID: 34779417). | |
| N345S | missense | unknown | PIK3CA N345S lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N345S has been identified in the scientific literature (PMID: 25769001, PMID: 28222664, PMID: 27283993), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| N345T | missense | gain of function - predicted | PIK3CA N345T lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N345T results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| N345Y | missense | unknown | PIK3CA N345Y lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N345Y has been identified in sequencing studies (PMID: 30181556, PMID: 29338072, PMID: 36053728), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| N347K | missense | unknown | PIK3CA N347K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N347K has been identified in sequencing studies (PMID: 29558370, PMID: 25078343), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| N457K | missense | unknown | PIK3CA N457K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N457K has been identified in the scientific literature (PMID: 29636477, PMID: 19844788), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| over exp | none | no effect | PIK3CA over exp indicates an over expression of the Pik3ca protein and/or mRNA. However, the mechanism causing the over expression is unspecified. | |
| P104L | missense | gain of function | PIK3CA P104L lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). P104L results in increased cell proliferation and migration and increased Akt phosphorylation compared to wild-type Pik3ca in culture (PMID: 34779417) and increased transformation ability in several different cell lines in culture (PMID: 29533785, PMID: 34779417). | |
| P104R | missense | unknown | PIK3CA P104R lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). P104R has been identified in sequencing studies (PMID: 30393068, PMID: 27502118), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| P104_V105del | deletion | unknown | PIK3CA P104_V105del results in the deletion of two amino acids in the PI3K-ABD domain of the Pik3ca protein from amino acids 104 to 105 (UniProt.org). P104_V105del has been identified in sequencing studies (PMID: 28178681), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| P124L | missense | gain of function - predicted | PIK3CA P124L does not lie within any known functional domains of the Pik3ca protein (UniProt.org). P124L results in activation of Pik3ca signaling as indicated by increased Akt phosphorylation in cell culture (PMID: 22430209), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| P217S | missense | unknown | PIK3CA P217S lies within the PI3K-RBD domain of the Pik3ca protein (UniProt.org). P217S has been identified in sequencing studies (PMID: 30503610), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| P298S | missense | unknown | PIK3CA P298S does not lie within any known functional domains of the Pik3ca protein (UniProt.org). P298S has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| P366R | missense | gain of function - predicted | PIK3CA P366R lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P366R results in increased transformation ability in two different cell lines (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| P377R | missense | unknown | PIK3CA P377R lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P377R has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| P421L | missense | unknown | PIK3CA P421L lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P421L has been identified in sequencing studies (PMID: 30275180, PMID: 20049837), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| P447_L455del | deletion | gain of function | PIK3CA P447_L455del results in the deletion of nine amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 447 to 455 (UniProt.org). P447_L455del confers a gain of function to the Pik3ca protein as demonstrated by transformation in culture and activation of the PI3K/Akt/Mtor pathway via increased phosphorylation of Akt, Erk, P70S6K, and P90RSK (PMID: 21266528, PMID: 29284706). | |
| P449L | missense | unknown | PIK3CA P449L lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P449L has been identified in sequencing studies (PMID: 29032825, PMID: 25759019), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| P449S | missense | unknown | PIK3CA P449S lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P449S has been identified in sequencing studies (PMID: 30503610), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| P449T | missense | gain of function - predicted | PIK3CA P449T lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P449T results in increased Pik3ca kinase activity in cell culture (PMID: 20530683), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| P449_L452del | deletion | unknown | PIK3CA P449_L452del results in the deletion of four amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 449 to 452 (UniProt.org). P449_L452del has been identified in sequencing studies (PMID: 30393068), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| P449_L455del | deletion | gain of function | PIK3CA P449_L455del results in the deletion of seven amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 449 to 455 (UniProt.org). P449_L455del results in increased Akt phosphorylation in cell culture relative to wild-type Pik3ca in culture (PMID: 21266528) and demonstrates increased transformation ability in two different cell lines, as compared to wild-type Pik3ca (PMID: 29533785). | |
| P449_L456del | deletion | unknown | PIK3CA P449_L456del results in the deletion of eight amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 449 to 465 (UniProt.org). P449_L456del has been identified in sequencing studies (PMID: 29316426), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| P466S | missense | unknown | PIK3CA P466S lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P466S has been identified in sequencing studies (PMID: 25759019, PMID: 22622578), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| P471A | missense | unknown | PIK3CA P471A lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P471A has been identified in sequencing studies (PMID: 30393068), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| P471L | missense | gain of function - predicted | PIK3CA P471L lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P471L results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| P487Q | missense | unknown | PIK3CA P487Q lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P487Q results in decreased cell proliferation and cell viability compared to wild-type Pik3ca in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown. | |
| P539R | missense | gain of function | PIK3CA P539R lies within the PIK helical domain of the Pik3ca protein (UniProt.org). P539R increases the stability of the Pik3ca protein, confers a gain of function, as indicated by constitutive phosphorylation of downstream targets Akt and S6, and is transforming in cell culture (PMID: 18951408, PMID: 17376864, PMID: 29533785). | |
| P539S | missense | unknown | PIK3CA P539S lies within the PIK helical domain of the Pik3ca protein (UniProt.org). P539S has been identified in the scientific literature (PMID: 34287479, PMID: 31254045, PMID: 22982087), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| positive | unknown | unknown | PIK3CA positive indicates the presence of the PIK3CA gene, mRNA and/or protein. | |
| Q1033R | missense | unknown | PIK3CA Q1033R lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). Q1033R has been identified in the scientific literature (PMID: 32193631), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| Q546E | missense | gain of function - predicted | PIK3CA Q546E lies within the PIK helical domain of the Pik3ca protein (UniProt.org). Q546E results in increased cell survival and transforming ability in culture (PMID: 26627007, PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| Q546H | missense | unknown | PIK3CA Q546H lies within the PIK helical domain of the Pik3ca protein (UniProt.org). Q546H has been identified in the scientific literature (PMID: 19148475, PMID: 28860563, PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| Q546K | missense | gain of function | PIK3CA Q546K lies within the PIK helical domain of the Pik3ca protein (UniProt.org, PMID: 17376864). Q546K confers a gain of function to Pik3ca as indicated by constitutive phosphorylation of downstream targets Akt and S6, and is transforming in cell culture (PMID: 17376864, PMID: 29533785). | |
| Q546L | missense | gain of function - predicted | PIK3CA Q546L lies within the PIK helical domain of the Pik3ca protein (UniProt.org). Q546L results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| Q546P | missense | gain of function | PIK3CA Q546P lies within the PIK helical domain of the Pik3ca protein (UniProt.org). Q546P results in increased phosphorylation of Akt, activation of downstream signaling, and is transforming in cell culture (PMID: 17376864, PMID: 29533785). | |
| Q546R | missense | gain of function | PIK3CA Q546R lies within the PIK helical domain of the Pik3ca protein (UniProt.org). Q546R results in increased cell proliferation, migration, and Akt phosphorylation (PMID: 34779417) and increased cell survival and transforming ability in culture (PMID: 26627007, PMID: 29533785, PMID: 34779417). | |
| Q546X | missense | unknown | PIK3CA Q546X indicates any PIK3CA missense mutation that results in replacement of the glutamine (Q) at amino acid 546 by a different amino acid. | |
| Q546_E547insQTS | insertion | unknown | PIK3CA Q546_E547insQTS results in the insertion of three amino acids in the PIK helical domain of the Pik3ca protein between amino acids 546 and 547 (UniProt.org). Q546_E547insQTS has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| Q60K | missense | no effect | PIK3CA Q60K lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). Q60K demonstrates kinase activity and transformation potential similar to wild-type Pik3ca protein (PMID: 18074223, PMID: 29533785). | |
| Q643H | missense | unknown | PIK3CA Q643H lies within the PIK helical domain of the Pik3ca protein (UniProt.org). Q643H has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| Q75E | missense | gain of function | PIK3CA Q75E lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). Q75E results in increased cell proliferation, migration, and increased phosphorylation of Akt compared to wild-type Pik3ca and is transforming in culture (PMID: 34779417). | |
| Q75K | missense | unknown | PIK3CA Q75K lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). Q75K has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| Q859H | missense | unknown | PIK3CA Q859H lies within the PI3K/PI4K catalytic domain of the Pik3ca protein (UniProt.org). Q859H has been associated with resistance to PI3K inhibitors in culture (PMID: 37916958), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | Y |
| Q859K | missense | unknown | PIK3CA Q859K lies within the PI3K/PI4K catalytic domain of the Pik3ca protein (UniProt.org). Q859K has been associated with resistance to PI3K inhibitors in culture (PMID: 37916958), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | Y |
| R1023L | missense | unknown | PIK3CA R1023L lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). R1023L has been identified in the scientific literature (PMID: 19844788), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R1023Q | missense | unknown | PIK3CA R1023Q lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). R1023Q has been identified in the scientific literature (PMID: 27699769, PMID: 36620501, PMID: 24092809), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R108C | missense | unknown | PIK3CA R108C lies within the p85 domain of the Pik3ca protein (PMID: 15016963). R108C results in increased transformation ability as compared to wild-type Pik3ca in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R108del | deletion | unknown | PIK3CA R108del results in the deletion of an amino acid in the p85 domain of the Pik3ca protein at amino acid 108 (PMID: 15016963). R108del has been identified in the scientific literature (PMID: 29181861, PMID: 30537512, PMID: 27161972), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| R108H | missense | gain of function | PIK3CA R108H lies within the p85 domain of the Pik3ca protein (PMID: 15016963). R108H results in increased phosphorylation of Akt, activation of downstream signaling in cell culture (PMID: 18829572), and demonstrates increased transformation ability in two different cell lines, as compared to wild-type Pik3ca (PMID: 29533785). | |
| R108L | missense | no effect - predicted | PIK3CA R108L lies within the p85 domain of the Pik3ca protein (PMID: 15016963). R108L results in similar cell proliferation and viability levels as wild-type Pik3ca in culture (PMID: 29533785), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| R108P | missense | unknown | PIK3CA R108P lies within the p85 domain of the Pik3ca protein (PMID: 15016963). R108P has been identified in sequencing studies (PMID: 15016963), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R108S | missense | unknown | PIK3CA R108S lies within the p85 domain of the Pik3ca protein (PMID: 15016963). R108S has been identified in the scientific literature (PMID: PMID: 31515834), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R115* | nonsense | loss of function - predicted | PIK3CA R115* results in a premature truncation of the Pik3ca protein at amino acid 115 of 1068 (UniProt.org). Due to the loss of PI3K/PI4K kinase domain (UniProt.org), R115* is predicted to lead to a loss of Pik3ca protein function. | |
| R115L | missense | gain of function | PIK3CA R115L does not lie within any known functional domains of the Pik3ca protein (UniProt.org). R115L confers a gain of function to the Pik3ca protein as demonstrated by increased cell growth, activation of the PI3K pathway (PMID: 23619167), and increased transformation ability in two different cell lines, as compared to wild-type Pik3ca (PMID: 29533785). | |
| R115P | missense | gain of function | PIK3CA R115P does not lie within any known functional domains of the Pik3ca protein (UniProt.org). R115P results in cell cycle distribution and apoptosis comparable to wild-type Pik3ca, but leads to increased Akt and Mtor phosphorylation, cyclin D1 and phosphorylated Rb levels, colony formation, and migration in cultured cells (PMID: 31632573). | |
| R115Q | missense | unknown | PIK3CA R115Q does not lie within any known functional domains of the Pik3ca protein (UniProt.org). R115Q has been identified in the scientific literature (PMID: 37925498), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| R335G | missense | no effect | PIK3CA R335G lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). R335G results in levels of cell proliferation, migration, and phosphorylation of Akt similar to wild-type Pik3ca and is not transforming in culture (PMID: 34779417). | |
| R357G | missense | unknown | PIK3CA R357G lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). R357G has been identified in sequencing studies (PMID: 23797736), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| R357L | missense | unknown | PIK3CA R357L lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). R357L has been identified in the scientific literature (PMID: 32578376), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| R357Q | missense | unknown | PIK3CA R357Q lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). R357Q has been identified in sequencing studies (PMID: 25233892, PMID: 23528559, PMID: 28446505), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R382K | missense | no effect - predicted | PIK3CA R382K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). R382K results in similar cell proliferation and viability levels as wild-type Pik3ca (PMID: 29533785), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| R38C | missense | gain of function | PIK3CA R38C lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). R38C confers a gain of function to Pik3ca, as indicated by increased phosphorylation of downstream targets Akt, GSK3-beta, FoxO1, FoxO3a, and S6 in cell culture (PMID: 18829572) and demonstrates increased transformation ability in two different cell lines, as compared to wild-type Pik3ca (PMID: 29533785). | |
| R38G | missense | unknown | PIK3CA R38G lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). R38G has been identified in the scientific literature (PMID: 27425854, PMID: 24140581), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R38H | missense | gain of function - predicted | PIK3CA R38H lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). R38H results in moderate increase of Pik3ca kinase activity and Akt phosphorylation, but is not transforming in culture in one study (PMID: 15930273), however in another study, increased transformation in two different cell lines (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| R38L | missense | unknown | PIK3CA R38L lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). R38L has been identified in sequencing studies (PMID: 28528867), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| R38S | missense | unknown | PIK3CA R38S lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). R38S is predicted to disrupt the enzymatic activity of Pik3ca by structural modeling (PMID: 18079394), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown. | |
| R398H | missense | no effect - predicted | PIK3CA R398H lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). R398H results in similar cell proliferation and viability levels as wild-type Pik3ca (PMID: 29533785), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| R401Q | missense | unknown | PIK3CA R401Q lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). R401Q has been identified in sequencing studies (PMID: 29575851), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| R519G | missense | no effect | PIK3CA R519G lies within the PIK helical domain of the Pik3ca protein (UniProt.org). R519G results in levels of cell proliferation, migration, and phosphorylation of Akt similar to wild-type Pik3ca and is not transforming in culture (PMID: 34779417). | |
| R524M | missense | unknown | PIK3CA R524M lies within the PIK helical domain of the Pik3ca protein (UniProt.org). R524M has been identified in the scientific literature (PMID: 16822308), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R617W | missense | unknown | PIK3CA R617W lies within the PIK helical domain of the Pik3ca protein (UniProt.org). R617W has been identified in sequencing studies (PMID: 23765252, PMID: 22653804), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R770Q | missense | unknown | PIK3CA R770Q lies within the PI3K/PI4K catalytic domain of the Pik3ca protein (UniProt.org). R770Q has been identified in the scientific literature (PMID: 26681737, PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R777M | missense | unknown | PIK3CA R777M lies within the PI3K/PI4K catalytic domain of the Pik3ca protein (UniProt.org). R777M has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R818C | missense | no effect - predicted | PIK3CA R818C lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). R818C results in similar levels of cell proliferation and viability to wild-type Pik3ca in culture (PMID: 29533785), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| R88L | missense | unknown | PIK3CA R88L lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). R88L has been identified in sequencing studies (PMID: 28002797, PMID: 27672108, PMID: 36299398), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R88Q | missense | gain of function | PIK3CA R88Q lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). R88Q confers a gain of function to the Pik3ca protein as indicated by increased phosphorylation of downstream targets Akt and S6, increased cell proliferation and migration, and is transforming in culture (PMID: 18829572, PMID: 29533785, PMID: 34779417). | |
| R916C | missense | unknown | PIK3CA R916C lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). R916C has been identified in the scientific literature (PMID: 30150660, PMID: 24356096, PMID: 26343386), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R93L | missense | unknown | PIK3CA R93L lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). R93L has been identified in sequencing studies (PMID: 26401016, PMID: 26080840), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| R93P | missense | gain of function - predicted | PIK3CA R93P lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). R93P has not been biochemically characterized, but is predicted to confer a gain of function on the Pik3ca protein as demonstrated by increased transformation ability in two different cell lines in culture (PMID: 29533785). | |
| R93Q | missense | no effect - predicted | PIK3CA R93Q lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). R93Q results in Akt phosphorylation levels similar to wild-type Pik3ca in cell culture (PMID: 21266528) and demonstrates decreased phosphorylation of S6 compared to PIK3CA H1047R in cultured cells (PMID: 26325104), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| R93W | missense | gain of function | PIK3CA R93W lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). R93W confers a gain of function on the Pik3ca protein as indicated by in increased phosphorylation of Akt in cell culture (PMID: 21266528) and increased transformation ability in two different cell lines, as compared to wild-type Pik3ca (PMID: 29533785). | |
| R975S | missense | unknown | PIK3CA R975S lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). The functional effect of R975S is conflicting, as it results in cell proliferation, viability, migration, and Akt phosphorylation levels similar to wild-type Pik3ca (PMID: 29533785, PMID: 34779417), but modestly increased cell proliferation in another study (PMID: 23619167), and therefore, its effect on Pik3ca protein function is unknown. | |
| R992P | missense | unknown | PIK3CA R992P lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). R992P has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| S332_L334del | deletion | loss of function - predicted | PIK3CA S332_L334del results in the deletion of three amino acids in the Pik3ca protein from amino acids 332 to 334 (UniProt.org). S332_L334del results in decreased transformation ability in two different cell lines compared to wild-type Pik3ca (PMID: 29533785), and therefore, is predicted to lead to a loss of Pik3ca protein function. | |
| S405F | missense | unknown | PIK3CA S405F lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). S405F has been identified in sequencing studies (PMID: 24695838, PMID: 27738081, PMID: 26226847), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| S405Y | missense | unknown | PIK3CA S405Y lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). S405Y has been identified in sequencing studies (PMID: 30337457), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| S553N | missense | unknown | PIK3CA S553N lies within the PIK helical domain of the Pik3ca protein (UniProt.org). S553N has been identified in sequencing studies (PMID: 24983367, PMID: 23665199, PMID: 23066039), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| S629C | missense | gain of function - predicted | PIK3CA S629C lies within the PIK helical domain of the Pik3ca protein (UniProt.org). S629C results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| S773F | missense | unknown | PIK3CA S773F lies within the PI3K/PI4K catalytic domain of the Pik3ca protein (UniProt.org). S773F has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| S900I | missense | unknown | PIK3CA S900I lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). S900I has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| T1025A | missense | gain of function - predicted | PIK3CA T1025A lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). T1025A results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| T1025I | missense | unknown | PIK3CA T1025I lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). T1025I has been identified in the scientific literature (PMID: 36916425, PMID: 25680416, PMID: 22949056), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| T1025K | missense | unknown | PIK3CA T1025K lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). T1025K has been identified in sequencing studies (PMID: 27672108), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| T1025N | missense | gain of function - predicted | PIK3CA T1025N lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). T1025N results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| T1025S | missense | gain of function | PIK3CA T1025S lies within the PI3K/PI4K domain in the Pik3ca protein (UniProt.org). T1025S confers a gain of function to the Pik3ca protein as indicated by constitutive activation of downstream signaling and transformation in cultured cells (PMID: 17376864). | |
| T1052K | missense | unknown | PIK3CA T1052K does not lie within any known functional domains of the Pik3ca protein (UniProt.org). T1052K has been identified in the scientific literature (PMID: 31410178, PMID: 21725289, PMID: 27672108), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| T324I | missense | unknown | PIK3CA T324I does not lie within any known functional domains of the Pik3ca protein (UniProt.org). T324I has been identified in the scientific literature (PMID: 16778113, PMID: 18376308, PMID: 18343945), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| T544I | missense | unknown | PIK3CA T544I lies within the PIK helical domain of the Pik3ca protein (UniProt.org). T544I has been identified in the scientific literature (PMID: 25073438, PMID: 26276776, PMID: 22357840), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| T544N | missense | unknown | PIK3CA T544N lies within the PIK helical domain of the Pik3ca protein (UniProt.org). T544N has been identified in the scientific literature (PMID: 26276776, PMID: 25722288, PMID: 22357840), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| V105_R108del | deletion | gain of function - predicted | PIK3CA V105_R108del results in the deletion of four amino acids in the Pik3ca protein from amino acids 105 to 108 (UniProt.org). V105_R108del has not been biochemically characterized, but results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| V146I | missense | unknown | PIK3CA V146I does not lie within any known functional domains of the Pik3ca protein (UniProt.org). V146I has been identified in the scientific literature (PMID: 26080840), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| V196I | missense | unknown | PIK3CA V196I lies within the PI3K-RBD domain of the Pik3ca protein (UniProt.org). V196I has been identified in sequencing studies (PMID: 32127467), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | |
| V344A | missense | unknown | PIK3CA V344A lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). V344A results in Akt phosphorylation similar to wild-type Pik3ca in culture (PMID: 21266528) but increased transformation in two different cell lines (PMID: 29533785), and therefore, its effect on Pik3ca protein function is unknown. | |
| V344G | missense | gain of function | PIK3CA V344G lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). V344G results in increased cell proliferation, migration, and Akt phosphorylation compared to wild-type Pik3ca in culture (PMID: 34779417) and increased transformation ability in several different cell lines in culture (PMID: 29533785, PMID: 34779417). | |
| V344M | missense | gain of function - predicted | PIK3CA V344M lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). V344M results in increased transformation ability in two different cell lines in culture (PMID: 29533785), and therefore, is predicted to lead to a gain of Pik3ca protein function. | |
| V356I | missense | no effect - predicted | PIK3CA V356I lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). V356I results in cell proliferation and viability levels similar to wild-type Pik3ca in culture (PMID: 29533785), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| V71I | missense | unknown | PIK3CA V71I lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). V71I results in increased levels of colony formation but leads to levels of cell migration and phosphorylation of Akt similar to wild-type Pik3ca and is not transforming in culture (PMID: 34779417), and therefore, its effect on Pik3ca protein function is unknown. | |
| V952A | missense | gain of function - predicted | PIK3CA V952A lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). V952A results in activation of Pik3ca signaling as indicated by increased phosphorylation of Akt and Mapk3/Mapk1 (Erk1/2), and confers resistance to Erbitux (cetuximab) in culture (PMID: 28424201), and therefore, is predicted to lead to a gain of Pik3ca protein function. | Y |
| V955G | missense | gain of function - predicted | PIK3CA V955G lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). V955G results in activation of Pik3ca signaling as indicated by increased phosphorylation of Akt and Mapk3/Mapk1 (Erk1/2), and confers resistance to Erbitux (cetuximab) in culture (PMID: 28424201), and therefore, is predicted to lead to a gain of Pik3ca protein function. | Y |
| V955I | missense | gain of function - predicted | PIK3CA V955I lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). V955I results in activation of Pik3ca signaling as indicated by increased phosphorylation of Akt and Mapk3/Mapk1 (Erk1/2), and confers resistance to Erbitux (cetuximab) in culture (PMID: 28424201), and therefore, is predicted to lead to a gain of Pik3ca protein function. | Y |
| W11C | missense | unknown | PIK3CA W11C does not lie within any known functional domains of the Pik3ca protein (UniProt.org). W11C has been identified in the scientific literature (PMID: 33754015, PMID: 37713162), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Jan 2024). | |
| W11L | missense | no effect - predicted | PIK3CA W11L does not lie within any known functional domains of the Pik3ca protein (UniProt.org). W11L results in cell proliferation and viability levels similar to wild-type Pik3ca in culture (PMID: 29533785), and therefore, is predicted to have no effect on Pik3ca protein function. | |
| W11_H14delinsY | indel | unknown | PIK3CA W11_H14delinsY results in a deletion of four amino acids of the Pik3ca protein from amino acids 11 to 14, combined with the insertion of a tyrosine (Y) at the same site (UniProt.org). W11_H14delinsY has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| W11_P18del | deletion | unknown | PIK3CA W11_P18del results in the deletion of eight amino acids of the Pik3ca protein from amino acids 11 to 18 (UniProt.org). W11_P18del has not been characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2023). | |
| W328S | missense | unknown | PIK3CA W328S does not lie within any known functional domains of the Pik3ca protein (UniProt.org). W328S results in increased levels of cell proliferation but leads to levels of cell migration and phosphorylation of Akt similar to wild-type Pik3ca and is not transforming in culture (PMID: 34779417), and therefore, its effect on Pik3ca protein function is unknown. | |
| W446_G460delinsC | indel | unknown | PIK3CA W446_G460delinsC results in a deletion of 15 amino acids in the C2 PI3K-type domain of the Pik3ca protein from amino acids 446 to 460, combined with the insertion of a cystine (C) at the same site (UniProt.org). W446_G460delinsC has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2024). | |
| W552G | missense | unknown | PIK3CA W552G lies within the PIK helical domain of the Pik3ca protein (UniProt.org). W552G has been identified in the scientific literature (PMID: 24983367, PMID: 16778113), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| W780R | missense | unknown | PIK3CA W780R lies within the PI3K/PI4K catalytic domain of the Pik3ca protein (UniProt.org). W780R has been associated with resistance to PI3K inhibitors in culture (PMID: 37916958), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023). | Y |
| wild-type | none | no effect | Wild-type PIK3CA indicates that no mutation has been detected within the PIK3CA gene. | |
| Y1021C | missense | unknown | PIK3CA Y1021C lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). Y1021C results in increased transformation ability compared to wild-type Pik3ca in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown. | |
| Y1021F | missense | unknown | PIK3CA Y1021F lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). Y1021F has been identified in the scientific literature (PMID: 22949056, PMID: 24983367, PMID: 24440717), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| Y1021H | missense | unknown | PIK3CA Y1021H lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). Y1021H has been identified in the scientific literature (PMID: 18084252, PMID: 28222664, PMID: 27302833), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Sep 2023). | |
| Y1021N | missense | unknown | PIK3CA Y1021N lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). Y1021N has been identified in the scientific literature (PMID: 22949056, PMID: 28502728, PMID: 15289301), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| Y165H | missense | unknown | PIK3CA Y165H does not lie within any known functional domains of the Pik3ca protein (UniProt.org). PIK3CA Y165H has been identified in sequencing studies (PMID: 27548314), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| Y272* | nonsense | loss of function - predicted | PIK3CA Y272* results in a premature truncation of the Pik3ca protein at amino acid 272 of 1068 (UniProt.org). Due to the loss of the PI3K/PI4K kinase domain (UniProt.org), Y272* is predicted to lead to a loss of Pik3ca protein function. | |
| Y56H | missense | unknown | PIK3CA Y56H lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). Y56H has not been characterized in the scientific literature and therefore, its effect on Pik3ca protein function is unknown (PubMed, Mar 2024). | |
| Y606C | missense | no effect | PIK3CA Y606C lies within the PIK helical domain of the Pik3ca protein (UniProt.org). Y606C results similar levels of cell proliferation, migration, and phosphorylation of Akt to wild-type Pik3ca and is not transforming in culture (PMID: 34779417). |
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