Protein / target
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Protein at a glance
Biological role
1-phosphatidylinositol-4,5-bisphosphate 3-kinase
Strongest disease association
Megalencephaly-capillary malformation-polymicrogyria syndrome
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
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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)
Domains and Gene Ontology detail (62)Hide
Domains & features
Gene Ontology
- Ccytoplasm
- Ccytosol
- Cintercalated disc
- Clamellipodium
- Cperinuclear region of cytoplasm
- Cphosphatidylinositol 3-kinase complex
- Cphosphatidylinositol 3-kinase complex, class IA
- Cphosphatidylinositol 3-kinase complex, class IB
- Cplasma membrane
- F1-phosphatidylinositol-3-kinase activity
- F1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity
- F1-phosphatidylinositol-4-phosphate 3-kinase activity
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Receptor tyrosine kinase signalling
- ·Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosph…
- ·PI3K events in ERBB4 signaling
- ·PI3K events in ERBB2 signaling
Cell migration
- ·Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosph…
- ·cell migration
- ·endothelial cell migration
Growth-factor signalling
- ·epidermal growth factor receptor signaling pathway
- ·insulin-like growth factor receptor signaling pathway
Cell proliferation & survival
- ·PIP3 activates AKT signaling
- ·CD28 dependent PI3K/Akt signaling
Oncogenic signalling
- ·Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
- ·Constitutive Signaling by Aberrant PI3K in Cancer
Immune signalling
- ·T cell receptor signaling pathway
- ·Interleukin-3, Interleukin-5 and GM-CSF signaling
View underlying pathways (25)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
4 medicines meet Open Targets' target-level approved-medicine definition; the 3 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
PI3-kinase p110-alpha subunit inhibitor
Indicated for Breast Neoplasms, Neoplasms
PI3-kinase p110-alpha subunit inhibitor
Indicated for Breast Neoplasms
PI3-kinase p110-alpha subunit inhibitor
Indicated for Neoplasms
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene PIK3CA
Gene-level evidence surfaced through the gene PIK3CAthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.
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Drug development
32 compounds recorded · 4 approved · 27 in clinical development · 1 earlier-stage
View all recorded compounds (10)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (10)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- Regulatory approval
Approval: Vijoice (EMA)
- CHMP positive opinion
CHMP positive opinion: Vijoice (EMA)
- Label change
Label change: ALPELISIB (NDA215039)
- Regulatory approval
Approval: Itovebi (EMA)
- Indication expanded
Indication expansion: ALPELISIB (NDA215039)
- Label change
Label change: ALPELISIB (NDA215039)
- Regulatory approval
Approval: ALPELISIB (NDA215039)
- New publicationAlpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1.
- Regulatory approval
Approval: Piqray (EMA)
- New publicationAlpelisib for <i>PIK3CA</i>-Mutated, Hormone Receptor-Positive Advanced Breast Cancer.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.
Related family literature
Papers about “Class Ia Phosphatidylinositol 3-Kinase” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.
via Class Ia Phosphatidylinositol 3-Kinase
Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.