Aliases: PI3K.
PIK3CA encodes p110alpha, the ~110 kDa catalytic subunit of class IA phosphoinositide 3-kinase (PI3Kalpha). It functions as an obligate heterodimer with a p85-family regulatory subunit (encoded by PIK3R1, PIK3R2 or PIK3R3), which stabilizes p110alpha and holds it in a basally inhibited state. Upon growth-factor stimulation, the regulatory subunit engages phosphotyrosine motifs on activated receptor tyrosine kinases or adaptor proteins such as IRS1, recruiting the enzyme to the inner leaflet of the plasma membrane; RAS-GTP provides an additional activating input via the RAS-binding domain. There, p110alpha transfers the gamma-phosphate of ATP to the 3-hydroxyl of the inositol ring of phosphatidylinositol-4,5-bisphosphate (PIP2), generating the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3). PIP3 recruits PH-domain effectors, notably AKT and PDK1, activating the PI3K-AKT-mTOR signaling axis that controls cell growth, survival, proliferation, metabolism and motility; the lipid phosphatase PTEN reverses the reaction. p110alpha is the principal class IA isoform transducing signals from insulin, IGF1 and many other receptor tyrosine kinases, and is essential for endothelial cell migration during vascular development. It also possesses a secondary protein-serine/threonine (auto)phosphorylation activity of less certain physiological significance. Somatic activating mutations (hotspots E542K, E545K, H1047R) make PIK3CA one of the most frequently mutated oncogenes, and mosaic activating variants cause overgrowth syndromes.
Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.
| Disorder | Relationship | Where the gene appears |
|---|---|---|
| Angiosarcoma | somatic driver somatic |
mechanism: Angiogenic Signaling Activation
scoped to subtype: Primary Breast Angiosarcoma
|
| Cowden Syndrome | susceptibility |
mechanism: PTEN Loss and PI3K/AKT/mTOR Pathway Activation
subtype: CS5
scoped to subtype: CS5
|
| Embryonal Rhabdomyosarcoma | cooperating somatic |
mechanism: RAS Pathway Activation
|
| Endometriosis | somatic driver somatic | |
| Focal Cortical Dysplasia Type II | causative somatic | |
| Gastric Adenocarcinoma | somatic driver somatic |
mechanism: EBV-Driven Hypermethylation and Checkpoint Ligand Amplification
scoped to subtype: EBV-positive
|
| Hemimegalencephaly | causative somatic |
mechanism: Postzygotic Somatic Variant in the PI3K-AKT3-mTOR Pathway
|
| Malignant Germ Cell Tumor of Ovary | somatic driver somatic |
mechanism: KIT and RAS-PI3K Oncogenic Signaling Activation
|
| Malignant Non-Dysgerminomatous Germ Cell Tumor Of Ovary | somatic driver somatic |
mechanism: Yolk Sac Tumor Molecular Alteration
|
| Triple-Negative Breast Cancer | somatic driver somatic | |
| Anal Canal Carcinoma |
untyped
Somatic Mutations
|
|
| angioosteohypertrophic syndrome |
untyped
Somatic activating mutation
somatic
|
mechanism: Somatic PIK3CA activation in malformed tissue
|
| BRAF V600E-Mutant Colorectal Cancer |
untyped
Co-occurring Somatic Mutations
|
|
| Breast Carcinoma |
untyped
Somatic activating mutation
somatic
|
|
| Cervical Adenocarcinoma |
untyped
Somatic Mutation / Amplification
|
|
| Cervical Cancer |
untyped
Somatic Mutations
|
|
| Chordoma |
untyped
Somatic Pathway Activation
|
|
| Clear Cell Ovarian Carcinoma |
untyped
Recurrent activating driver mutation
|
|
| CLOVES Syndrome |
untyped
Causative
somatic
|
mechanism: Constitutive PI3K Activation
|
| Cutaneous Squamous Cell Carcinoma |
untyped
Somatic Mutation
|
|
| EBV-Associated Gastric Cancer |
untyped
Somatic Mutation
|
|
| Endometrial Carcinoma |
untyped
Somatic activating mutation
|
mechanism: PTEN PI3K Pathway Dysregulation
|
| Endometrial Endometrioid Adenocarcinoma |
untyped
Recurrent somatic PI3K-pathway driver alteration
somatic
|
mechanism: PTEN PI3K Pathway Dysregulation
|
| ER-Positive Breast Cancer |
untyped
Somatic Mutations
|
|
| Esophageal Squamous Cell Carcinoma |
untyped
Oncogenic Signaling Activation
|
|
| Gallbladder Cancer |
untyped
Somatic Gain-of-Function Mutation
|
|
| HER2-Positive Breast Cancer |
untyped
Co-occurring Mutations
|
|
| HER2-Positive Gastric Cancer |
untyped
Potential Resistance Mechanism
|
|
| HPV-Negative Head and Neck Cancer |
untyped
Somatic Mutations
|
|
| HPV-Positive Head and Neck Cancer |
untyped
Somatic Mutations
|
|
| Laryngeal Squamous Cell Carcinoma |
untyped
Somatic mutation
|
|
| Meningioma |
untyped
Less common PI3K-pathway alteration
|
mechanism: Non-NF2 Driver Mutation Subgroups
|
| Oral Cavity Squamous Cell Carcinoma |
untyped
Amplification/Activating Mutations
|
mechanism: PI3K-AKT-mTOR Pathway Activation
|
| Ovarian Endometrioid Carcinoma |
untyped
Activating mutation
|
mechanism: PI3K-AKT Pathway Activation
|
| Pancreatic Neuroendocrine Tumor |
untyped
Activating mutations in ~1.4% of pNETs; mTOR pathway component
|
|
| PIK3CA-Mutant Breast Cancer |
untyped
Somatic Activating Mutations
somatic
gain of function
|
mechanism: PIK3CA Oncogenic Mutations
|
| Squamous Cell Carcinoma of Penis |
untyped
Somatic Driver Mutation
somatic
|
mechanism: Somatic Cell-Cycle Driver Alteration
|
| Transitional Cell Carcinoma | untyped somatic | |
| Vulvar Carcinoma |
untyped
Somatic Activating Mutation
|
mechanism: PIK3CA-Activated HPV-Associated Signaling
|
| BRAF V600E-Mutant Non-Small Cell Lung Cancer | no genetic record |
mechanism: Cooperating Tumor-Suppressor and Lineage-State Alterations
|
An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.
| ClinGen disease | MOI | Classification | dismech entry |
|---|---|---|---|
| hereditary breast carcinoma MONDO:0016419 | AD | Refuted 2023-12-21 |
no dismech entry |
Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.