UniProt functional annotation for P42336



	UniProt functional annotation for P42336

UniProt code: P42336.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396, PubMed:23936502, PubMed:28676499). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396, PubMed:28676499). PIP3 plays a key role by recruiting PH domain- containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others (PubMed:23936502, PubMed:28676499). Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity). {ECO:0000250|UniProtKB:P42337, ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:21708979, ECO:0000269|PubMed:23936502, ECO:0000269|PubMed:26593112, ECO:0000269|PubMed:28676499}.

Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:21292, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57836, ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.153; Evidence={ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:28676499}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293; Evidence={ECO:0000305|PubMed:15135396, ECO:0000305|PubMed:28676499};

Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216; EC=2.7.1.137; Evidence={ECO:0000269|PubMed:23936502}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710; Evidence={ECO:0000305|PubMed:23936502};

Catalytic activity: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:23936502, ECO:0000269|PubMed:28676499}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; Evidence={ECO:0000305|PubMed:23936502, ECO:0000305|PubMed:28676499};

Catalytic activity: Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- bisphosphate) + ATP = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo- inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:55632, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:83416, ChEBI:CHEBI:83419, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:28676499}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55633; Evidence={ECO:0000305|PubMed:28676499};

Catalytic activity: Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero- 3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2- (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo- inositol 3,4,5-triphosphate) + ADP + H(+); Xref=Rhea:RHEA:43396, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77137, ChEBI:CHEBI:83243, ChEBI:CHEBI:456216; Evidence={ECO:0000305|PubMed:15135396}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43397; Evidence={ECO:0000305|PubMed:15135396};

Biophysicochemical properties: Kinetic parameters: KM=1.77 uM for PIP2 (1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo- inositol-4,5-bisphosphate) {ECO:0000269|PubMed:28676499}; KM=2.00 uM for ATP {ECO:0000269|PubMed:28676499}; Vmax=1.70 pmol/min/ng enzyme for the phosphorylation of PIP2 (1,2- dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) {ECO:0000269|PubMed:28676499};

Pathway: Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis. {ECO:0000305|PubMed:15135396, ECO:0000305|PubMed:28676499}.

Subunit: Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3) (PubMed:26593112). Interacts with IRS1 in nuclear extracts (By similarity). Interacts with RUFY3 (By similarity). Interacts with RASD2 (By similarity). Interacts with APPL1. Interacts with HRAS and KRAS (By similarity). Interaction with HRAS/KRAS is required for PI3K pathway signaling and cell proliferation stimulated by EGF and FGF2 (By similarity). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (PubMed:23676467). {ECO:0000250|UniProtKB:P42337, ECO:0000269|PubMed:23676467, ECO:0000269|PubMed:26593112}.

Domain: The PI3K-ABD domain and the PI3K-RBD domain interact with the PI3K/PI4K kinase domain. The C2 PI3K-type domain may facilitate the recruitment to the plasma membrane. The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1, and the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1. {ECO:0000269|PubMed:18079394, ECO:0000269|PubMed:19805105}.

Disease: Note=PIK3CA mutations are involved in various type of cancer. Most of the cancer-associated mutations are missense mutations and map to one of the three hotspots: Glu-542; Glu-545 and His-1047. Mutated isoforms participate in cellular transformation and tumorigenesis induced by oncogenic receptor tyrosine kinases (RTKs) and HRAS/KRAS. Interaction with HRAS/KRAS is required for Ras-driven tumor formation. Mutations increasing the lipid kinase activity are required for oncogenic signaling. The protein kinase activity may not be required for tumorigenesis. {ECO:0000269|PubMed:15016963, ECO:0000269|PubMed:15289301, ECO:0000269|PubMed:15520168, ECO:0000269|PubMed:15712344, ECO:0000269|PubMed:15784156, ECO:0000269|PubMed:15924253, ECO:0000269|PubMed:15930273, ECO:0000269|PubMed:15994075, ECO:0000269|PubMed:16114017, ECO:0000269|PubMed:16322209, ECO:0000269|PubMed:16353168, ECO:0000269|PubMed:16432179, ECO:0000269|PubMed:16533766, ECO:0000269|PubMed:17673550, ECO:0000269|PubMed:19805105, ECO:0000269|PubMed:21708979, ECO:0000269|PubMed:22658544, ECO:0000269|PubMed:22729224}.

Disease: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:15930273, ECO:0000269|PubMed:15994075}. Note=The gene represented in this entry may be involved in disease pathogenesis.

Disease: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:16353168}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Disease: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. {ECO:0000269|PubMed:15520168}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Disease: Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. {ECO:0000269|PubMed:15608678}. Note=The gene represented in this entry may be involved in disease pathogenesis.

Disease: Keratosis, seborrheic (KERSEB) [MIM:182000]: A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance. {ECO:0000269|PubMed:17673550}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) [MIM:602501]: A syndrome characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria. {ECO:0000269|PubMed:22729224, ECO:0000269|PubMed:26593112}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) [MIM:612918]: A sporadically occurring, non- hereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. It is defined by four main clinical findings: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities. The presence of truncal overgrowth and characteristic patterned macrodactyly at birth differentiates CLOVE from other syndromic forms of overgrowth. {ECO:0000269|PubMed:22658544}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Cowden syndrome 5 (CWS5) [MIM:615108]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. {ECO:0000269|PubMed:23246288}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: CLAPO syndrome (CLAPO) [MIM:613089]: A syndrome characterized by capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry of face and limbs and partial or generalised overgrowth. {ECO:0000269|PubMed:29446767}. Note=The disease may be caused by variants affecting the gene represented in this entry. The tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism. {ECO:0000269|PubMed:29446767}.

Disease: Macrodactyly (MADAC) [MIM:155500]: A congenital anomaly characterized by fibrofatty tissue enlargement and bony overgrowth affecting the digits or the entire hand or foot. {ECO:0000269|PubMed:23100325}. Note=The disease may be caused by variants affecting the gene represented in this entry. The tissue distribution of the clinical manifestations in MADAC seems to follow a pattern of somatic mosaicism. {ECO:0000269|PubMed:23100325}.

Miscellaneous: The avian sarcoma virus 16 genome encodes an oncogene derived from PIK3CA. {ECO:0000305|PubMed:18418043}.

Similarity: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE- ProRule:PRU00877, ECO:0000255|PROSITE-ProRule:PRU00879, ECO:0000255|PROSITE-ProRule:PRU00880}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396, PubMed:23936502, PubMed:28676499). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396, PubMed:28676499). PIP3 plays a key role by recruiting PH domain- containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others (PubMed:23936502, PubMed:28676499). Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity). {ECO:0000250\|UniProtKB:P42337, ECO:0000269\|PubMed:15135396, ECO:0000269\|PubMed:21708979, ECO:0000269\|PubMed:23936502, ECO:0000269\|PubMed:26593112, ECO:0000269\|PubMed:28676499}.


Catalytic activity:		Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:21292, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57836, ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.153; Evidence={ECO:0000269\|PubMed:15135396, ECO:0000269\|PubMed:28676499}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293; Evidence={ECO:0000305\|PubMed:15135396, ECO:0000305\|PubMed:28676499};
Catalytic activity:		Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216; EC=2.7.1.137; Evidence={ECO:0000269\|PubMed:23936502}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710; Evidence={ECO:0000305\|PubMed:23936502};
Catalytic activity:		Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269\|PubMed:23936502, ECO:0000269\|PubMed:28676499}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; Evidence={ECO:0000305\|PubMed:23936502, ECO:0000305\|PubMed:28676499};
Catalytic activity:		Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- bisphosphate) + ATP = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo- inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:55632, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:83416, ChEBI:CHEBI:83419, ChEBI:CHEBI:456216; Evidence={ECO:0000269\|PubMed:28676499}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55633; Evidence={ECO:0000305\|PubMed:28676499};
Catalytic activity:		Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero- 3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2- (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo- inositol 3,4,5-triphosphate) + ADP + H(+); Xref=Rhea:RHEA:43396, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77137, ChEBI:CHEBI:83243, ChEBI:CHEBI:456216; Evidence={ECO:0000305\|PubMed:15135396}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43397; Evidence={ECO:0000305\|PubMed:15135396};
Biophysicochemical properties:		Kinetic parameters: KM=1.77 uM for PIP2 (1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo- inositol-4,5-bisphosphate) {ECO:0000269\|PubMed:28676499}; KM=2.00 uM for ATP {ECO:0000269\|PubMed:28676499}; Vmax=1.70 pmol/min/ng enzyme for the phosphorylation of PIP2 (1,2- dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) {ECO:0000269\|PubMed:28676499};
Pathway:		Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis. {ECO:0000305\|PubMed:15135396, ECO:0000305\|PubMed:28676499}.
Subunit:		Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3) (PubMed:26593112). Interacts with IRS1 in nuclear extracts (By similarity). Interacts with RUFY3 (By similarity). Interacts with RASD2 (By similarity). Interacts with APPL1. Interacts with HRAS and KRAS (By similarity). Interaction with HRAS/KRAS is required for PI3K pathway signaling and cell proliferation stimulated by EGF and FGF2 (By similarity). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (PubMed:23676467). {ECO:0000250\|UniProtKB:P42337, ECO:0000269\|PubMed:23676467, ECO:0000269\|PubMed:26593112}.
Domain:		The PI3K-ABD domain and the PI3K-RBD domain interact with the PI3K/PI4K kinase domain. The C2 PI3K-type domain may facilitate the recruitment to the plasma membrane. The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1, and the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1. {ECO:0000269\|PubMed:18079394, ECO:0000269\|PubMed:19805105}.
Disease:		Note=PIK3CA mutations are involved in various type of cancer. Most of the cancer-associated mutations are missense mutations and map to one of the three hotspots: Glu-542; Glu-545 and His-1047. Mutated isoforms participate in cellular transformation and tumorigenesis induced by oncogenic receptor tyrosine kinases (RTKs) and HRAS/KRAS. Interaction with HRAS/KRAS is required for Ras-driven tumor formation. Mutations increasing the lipid kinase activity are required for oncogenic signaling. The protein kinase activity may not be required for tumorigenesis. {ECO:0000269\|PubMed:15016963, ECO:0000269\|PubMed:15289301, ECO:0000269\|PubMed:15520168, ECO:0000269\|PubMed:15712344, ECO:0000269\|PubMed:15784156, ECO:0000269\|PubMed:15924253, ECO:0000269\|PubMed:15930273, ECO:0000269\|PubMed:15994075, ECO:0000269\|PubMed:16114017, ECO:0000269\|PubMed:16322209, ECO:0000269\|PubMed:16353168, ECO:0000269\|PubMed:16432179, ECO:0000269\|PubMed:16533766, ECO:0000269\|PubMed:17673550, ECO:0000269\|PubMed:19805105, ECO:0000269\|PubMed:21708979, ECO:0000269\|PubMed:22658544, ECO:0000269\|PubMed:22729224}.
Disease:		Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269\|PubMed:15930273, ECO:0000269\|PubMed:15994075}. Note=The gene represented in this entry may be involved in disease pathogenesis.
Disease:		Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269\|PubMed:16353168}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease:		Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. {ECO:0000269\|PubMed:15520168}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease:		Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. {ECO:0000269\|PubMed:15608678}. Note=The gene represented in this entry may be involved in disease pathogenesis.
Disease:		Keratosis, seborrheic (KERSEB) [MIM:182000]: A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance. {ECO:0000269\|PubMed:17673550}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) [MIM:602501]: A syndrome characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria. {ECO:0000269\|PubMed:22729224, ECO:0000269\|PubMed:26593112}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) [MIM:612918]: A sporadically occurring, non- hereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. It is defined by four main clinical findings: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities. The presence of truncal overgrowth and characteristic patterned macrodactyly at birth differentiates CLOVE from other syndromic forms of overgrowth. {ECO:0000269\|PubMed:22658544}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Cowden syndrome 5 (CWS5) [MIM:615108]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. {ECO:0000269\|PubMed:23246288}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		CLAPO syndrome (CLAPO) [MIM:613089]: A syndrome characterized by capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry of face and limbs and partial or generalised overgrowth. {ECO:0000269\|PubMed:29446767}. Note=The disease may be caused by variants affecting the gene represented in this entry. The tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism. {ECO:0000269\|PubMed:29446767}.
Disease:		Macrodactyly (MADAC) [MIM:155500]: A congenital anomaly characterized by fibrofatty tissue enlargement and bony overgrowth affecting the digits or the entire hand or foot. {ECO:0000269\|PubMed:23100325}. Note=The disease may be caused by variants affecting the gene represented in this entry. The tissue distribution of the clinical manifestations in MADAC seems to follow a pattern of somatic mosaicism. {ECO:0000269\|PubMed:23100325}.
Miscellaneous:		The avian sarcoma virus 16 genome encodes an oncogene derived from PIK3CA. {ECO:0000305\|PubMed:18418043}.
Similarity:		Belongs to the PI3/PI4-kinase family. {ECO:0000255\|PROSITE- ProRule:PRU00877, ECO:0000255\|PROSITE-ProRule:PRU00879, ECO:0000255\|PROSITE-ProRule:PRU00880}.