HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PIK3CA
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
Chromosome 3 · 3q26.32
NCBI Gene: 5290Ensembl: ENSG00000121879.7HGNC: HGNC:8975UniProt: P42336
1,720PubMed Papers
32Diseases
32Drugs
111Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneKinaseOncogene
RESEARCH IMPACT
Highly StudiedTrendingVariant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
phosphatidylinositol 3-kinase/protein kinase B signal transductionpositive regulation of protein localization to membrane1-phosphatidylinositol-4,5-bisphosphate 3-kinase activitypositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionmegalencephaly-capillary malformation-polymicrogyria syndromeCLOVE syndromeCLOVES syndromePIK3CA-related overgrowth spectrum
✦AI Summary

PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), a lipid kinase that phosphorylates phosphatidylinositol and its derivatives at the inositol ring position 3 to generate 3-phosphoinositides 123. Specifically, PIK3CA converts PtdIns(4,5)P2 to phosphatidylinositol 3,4,5-trisphosphate (PIP3), which recruits PH domain-containing proteins like AKT1 and PDPK1 to activate signaling cascades controlling cell growth, survival, proliferation, and motility 134. Beyond lipid kinase activity, PIK3CA displays serine-protein kinase activity, phosphorylating regulatory proteins and autophosphorylating p85α 2. PIK3CA functions downstream of receptor tyrosine kinases responding to growth factors (EGF, insulin, IGF1, VEGFA, PDGF) and is essential for vascular development and endothelial cell migration 4. PIK3CA mutations and amplifications drive oncogenic hyperactivation of the PI3K/AKT/mTOR survival pathway in multiple solid tumors 5, occurring in 25-40% of breast cancers with hotspots in exons 9 and 20 6. PIK3CA alterations associate with poor prognosis and serve as biomarkers for targeted therapy 78. PI3K pathway inhibitors, including the specific inhibitor alpelisib, demonstrate clinical efficacy in treating PIK3CA-mutant cancers 94.

Sources cited
1
PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), a lipid kinase that phosphorylates phosphatidylinositol and its derivatives at the inositol ring position 3 to generate 3-phosphoinositides , , .
PMID: 23936502
2
Specifically, PIK3CA converts PtdIns(4,5)P2 to phosphatidylinositol 3,4,5-trisphosphate (PIP3), which recruits PH domain-containing proteins like AKT1 and PDPK1 to activate signaling cascades controlling cell growth, survival, proliferation, and motility , , .
PMID: 25688137
3
PIK3CA mutations and amplifications drive oncogenic hyperactivation of the PI3K/AKT/mTOR survival pathway in multiple solid tumors , occurring in 25-40% of breast cancers with hotspots in exons 9 and 20 .
PMID: 31988478
4
PIK3CA mutations and amplifications drive oncogenic hyperactivation of the PI3K/AKT/mTOR survival pathway in multiple solid tumors , occurring in 25-40% of breast cancers with hotspots in exons 9 and 20 .
PMID: 26921096
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ32
megalencephaly-capillary malformation-polymicrogyria syndromeOpen Targets
0.85Strong
CLOVE syndromeOpen Targets
0.79Strong
CLOVES syndromeOpen Targets
0.79Strong
PIK3CA-related overgrowth spectrumOpen Targets
0.77Strong
Cowden syndrome 5Open Targets
0.75Strong
breast cancerOpen Targets
0.75Strong
pik3ca related overgrowth spectrumOpen Targets
0.75Strong
ovarian cancerOpen Targets
0.73Strong
seborrheic keratosisOpen Targets
0.73Strong
breast adenocarcinomaOpen Targets
0.73Strong
CLAPO syndromeOpen Targets
0.72Strong
megalodactylyOpen Targets
0.68Moderate
hepatocellular carcinomaOpen Targets
0.67Moderate
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genesOpen Targets
0.67Moderate
non-small cell lung carcinomaOpen Targets
0.67Moderate
ovarian neoplasmOpen Targets
0.67Moderate
colorectal adenocarcinomaOpen Targets
0.66Moderate
Cowden diseaseOpen Targets
0.65Moderate
colorectal cancerOpen Targets
0.63Moderate
urinary bladder cancerOpen Targets
0.63Moderate
Breast cancerUniProt
Cerebral cavernous malformations 4UniProt
CLAPO syndromeUniProt
Colorectal cancerUniProt
Congenital lipomatous overgrowth, vascular malformations, and epidermal neviUniProt
Cowden syndrome 5UniProt
Hemifacial myohyperplasiaUniProt
Hepatocellular carcinomaUniProt
Keratosis, seborrheicUniProt
MacrodactylyUniProt
Megalencephaly-capillary malformation-polymicrogyria syndromeUniProt
Ovarian cancerUniProt
Pathogenic Variants111
NM_006218.4(PIK3CA):c.325GAA[1] (p.Glu110del)Likely pathogenic
PIK3CA related overgrowth syndrome|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes|not provided|CLOVES syndrome|Angioosteohypertrophic syndrome|PIK3CA-related disorder|Rare venous malformation|Neoplasm|Inborn genetic diseases|Embryonal rhabdomyosarcoma|Giant cell glioblastoma
★★★☆2025→ Residue 110
NM_006218.4(PIK3CA):c.1624G>A (p.Glu542Lys)Pathogenic
CLOVES syndrome|Ovarian neoplasm|Non-small cell lung carcinoma|not provided|CLAPO syndrome|Lip and oral cavity carcinoma|Abnormal cardiovascular system morphology|Cerebrofacial Vascular Metameric Syndrome (CVMS)|CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes|PIK3CA related overgrowth syndrome|PIK3CA-related overgrowth|Cowden syndrome|PIK3CA-related disorder|Neoplasm|Megalencephaly-capillary malformation-polymicrogyria syndrome|Rare venous malformation|HEMIFACIAL MYOHYPERPLASIA, SOMATIC|Alveolar rhabdomyosarcoma|Diffuse midline glioma, H3 K27M-mutant|Rosette-forming glioneuronal tumor|Vascular malformation|Glioma|Cervical squamous cell carcinoma
★★★☆2022→ Residue 542
NM_006218.4(PIK3CA):c.2176G>A (p.Glu726Lys)Pathogenic
not provided|Inborn genetic diseases|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes|Cowden syndrome|Neoplasm|Megalencephaly-capillary malformation-polymicrogyria syndrome|PIK3CA related overgrowth syndrome|Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype|Dysembryoplastic neuroepithelial tumor
★★★☆2022→ Residue 726
NM_006218.4(PIK3CA):c.2740G>A (p.Gly914Arg)Pathogenic
Megalencephaly-capillary malformation-polymicrogyria syndrome|not provided|Abnormal cardiovascular system morphology|Cowden syndrome 5|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes|Cowden syndrome|Angioosteohypertrophic syndrome|Abnormal cerebral morphology|PIK3CA related overgrowth syndrome|PIK3CA-related disorder|CLOVES syndrome|Inborn genetic diseases|PIK3C1-related disorder
★★★☆2022→ Residue 914
NM_006218.4(PIK3CA):c.3140A>G (p.His1047Arg)Pathogenic
Breast adenocarcinoma|Carcinoma of colon|Hepatocellular carcinoma|Non-small cell lung carcinoma|Seborrheic keratosis|OVARIAN CANCER, EPITHELIAL, SOMATIC|CLOVES syndrome|Ovarian neoplasm|PIK3CA related overgrowth syndrome|Neoplasm|Rosette-forming glioneuronal tumor|MACRODACTYLY, SOMATIC|not provided|Lip and oral cavity carcinoma|Abnormal cardiovascular system morphology|Congenital macrodactylia|Segmental undergrowth associated with mainly venous malformation with capillary component|Segmental undergrowth associated with lymphatic malformation|Megalencephaly-capillary malformation-polymicrogyria syndrome|CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC|CLAPO syndrome|Cerebrofacial Vascular Metameric Syndrome (CVMS)|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes|Breast carcinoma|Klippel-Trenaunay-like-Syndrome|Gastric cancer|Rare combined vascular malformation|Rare venous malformation|PIK3CA-related disorder|Glioma|Colorectal cancer|Adenoid cystic carcinoma|Embryonal rhabdomyosarcoma|Diffuse glioma, H3 G34 mutant|Neuroblastoma|Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype|Cavernous lymphangioma|PIK3CA-Related Overgrowth Spectrum Disorders|Nasopharyngeal carcinoma|Diffuse midline glioma, H3 K27M-mutant|Cervical squamous cell carcinoma
★★★☆2022→ Residue 1047
NM_006218.4(PIK3CA):c.323G>A (p.Arg108His)Pathogenic
not provided|not specified|Megalencephaly-capillary malformation-polymicrogyria syndrome|Cowden syndrome|See cases|Neoplasm|Inborn genetic diseases|Embryonal rhabdomyosarcoma
★★☆☆2025→ Residue 108
NM_006218.4(PIK3CA):c.263G>A (p.Arg88Gln)Pathogenic
Ovarian neoplasm|not provided|Cowden syndrome|Cowden syndrome 5|PIK3CA related overgrowth syndrome|Abnormal cerebral morphology|Neoplasm|CLOVES syndrome|Megalencephaly-capillary malformation-polymicrogyria syndrome|Pilocytic astrocytoma|Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype|Medulloblastoma WNT activated|Giant cell glioblastoma
★★☆☆2025→ Residue 88
NM_006218.4(PIK3CA):c.3061T>C (p.Tyr1021His)Pathogenic
PIK3CA related overgrowth syndrome|Cowden syndrome
★★☆☆2025→ Residue 1021
NM_006218.4(PIK3CA):c.1132T>C (p.Cys378Arg)Pathogenic
CLOVES syndrome|Megalencephaly-capillary malformation-polymicrogyria syndrome|Capillary malformation|Angioosteohypertrophic syndrome|Inborn genetic diseases|Medulloblastoma WNT activated
★★☆☆2025→ Residue 378
NM_006218.4(PIK3CA):c.344G>C (p.Arg115Pro)Pathogenic
CLAPO syndrome|MACRODACTYLY, SOMATIC|Megalencephaly-capillary malformation-polymicrogyria syndrome|PIK3CA-related disorder|PIK3CA related overgrowth syndrome|not provided
★★☆☆2025→ Residue 115
NM_006218.4(PIK3CA):c.1634A>C (p.Glu545Ala)Pathogenic
Hepatocellular carcinoma|Ovarian neoplasm|Abnormal cardiovascular system morphology|Dysembryoplastic neuroepithelial tumor|Neoplasm|Primary central nervous system lymphoma|PIK3CA related overgrowth syndrome
★★☆☆2025→ Residue 545
NM_006218.4(PIK3CA):c.1637A>C (p.Gln546Pro)Pathogenic
Ovarian neoplasm|PIK3CA related overgrowth syndrome|Neoplasm|Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
★★☆☆2025→ Residue 546
NM_006218.4(PIK3CA):c.1133G>A (p.Cys378Tyr)Pathogenic
Megalencephaly-capillary malformation-polymicrogyria syndrome|PIK3CA related overgrowth syndrome|Cowden syndrome|PIK3CA-related disorder|Epidermal nevus|Diffuse midline glioma, H3 K27M-mutant|not provided
★★☆☆2025→ Residue 378
NM_006218.4(PIK3CA):c.1356AGA[1] (p.Glu453del)Pathogenic
Megalencephaly-capillary malformation-polymicrogyria syndrome|not provided|Cowden syndrome|PIK3CA-related disorder
★★☆☆2025→ Residue 453
NM_006218.4(PIK3CA):c.311C>T (p.Pro104Leu)Pathogenic
PIK3CA related overgrowth syndrome|Cowden syndrome|not provided|PIK3CA-related disorder|Vascular malformation
★★☆☆2025→ Residue 104
NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys)Pathogenic
Ovarian neoplasm|Abnormal cardiovascular system morphology|CLOVES syndrome|Megalencephaly-capillary malformation-polymicrogyria syndrome|not provided|Cowden syndrome|PIK3CA-related disorder|PIK3CA related overgrowth syndrome|Neoplasm
★★☆☆2025→ Residue 453
NM_006218.4(PIK3CA):c.3145G>A (p.Gly1049Ser)Pathogenic
not provided|Megalencephaly-capillary malformation-polymicrogyria syndrome
★★☆☆2025→ Residue 1049
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys)Pathogenic
Carcinoma of colon|Seborrheic keratosis|Breast adenocarcinoma|OVARIAN CANCER, EPITHELIAL, SOMATIC|Non-small cell lung carcinoma|Megalencephaly-capillary malformation-polymicrogyria syndrome|Sarcoma|Ovarian neoplasm|not provided|CLOVES syndrome|PIK3CA related overgrowth syndrome|Gallbladder cancer|Abnormal cardiovascular system morphology|Segmental undergrowth associated with lymphatic malformation|Eccrine angiomatous hamartoma|Cerebrofacial Vascular Metameric Syndrome (CVMS)|Gastric cancer|HEMIFACIAL MYOHYPERPLASIA, SOMATIC|PIK3CA overgrowth syndrome|Neoplasm|Angioosteohypertrophic syndrome|Rare venous malformation|Rare combined vascular malformation|PIK3CA-related disorder|Embryonal rhabdomyosarcoma|Congenital fibrosarcoma|Cerebral cavernous malformation|Adenocarcinoma of the large intestine|Lymphatic malformation|IDH-wildtype glioblastoma|Rosette-forming glioneuronal tumor|Medulloblastoma WNT activated|Cervical squamous cell carcinoma
★★☆☆2025→ Residue 545
NM_006218.4(PIK3CA):c.1093G>A (p.Glu365Lys)Pathogenic
not provided|Ovarian neoplasm|Cowden syndrome|Megalencephaly-capillary malformation-polymicrogyria syndrome|Angioosteohypertrophic syndrome|PIK3CA-related disorder|PIK3CA related overgrowth syndrome|Neoplasm
★★☆☆2024→ Residue 365
NM_006218.4(PIK3CA):c.2816A>G (p.Asp939Gly)Pathogenic
See cases|Segmental undergrowth associated with mainly venous malformation with capillary component|Angioosteohypertrophic syndrome|Megalencephaly-capillary malformation-polymicrogyria syndrome|not provided
★★☆☆2024→ Residue 939
View on ClinVar ↗
Drug Targets32
ALPELISIBApproved
PI3-kinase p110-alpha subunit inhibitor
breast cancer
APITOLISIBPhase II
PI3-kinase class I inhibitor
non-Hodgkins lymphoma
AZD-6482Phase I
PI3-kinase class I inhibitor
BAY-1082439Phase I
PI3-kinase p110-alpha subunit inhibitor
BGT-226Phase I/II
PI3-kinase class I inhibitor
BUPARLISIBPhase III
PI3-kinase class I inhibitor
breast cancer
COPANLISIBApproved
PI3-kinase p110-alpha subunit inhibitor
follicular lymphoma
COPANLISIB HYDROCHLORIDEApproved
PI3-kinase p110-alpha subunit inhibitor
follicular lymphoma
DACTOLISIBPhase III
PI3-kinase class I inhibitor
Respiratory tract infection
DS-7423Phase I
Serine/threonine-protein kinase mTOR inhibitor
FIMEPINOSTATPhase II
Histone deacetylase inhibitor
lymphoma
GEDATOLISIBPhase III
PI3-kinase class I inhibitor
breast cancer
GSK-1059615Phase I
PI3-kinase class I inhibitor
breast cancer
INAVOLISIBApproved
PI3-kinase p110-alpha subunit inhibitor
breast neoplasm
IZORLISIBPhase I/II
PI3-kinase class I inhibitor
colorectal cancer
OMIPALISIBPhase I
PI3-kinase class I inhibitor
lymphoma
PANULISIBPhase I
PI3-kinase class I inhibitor
PAXALISIBPhase II
PI3-kinase class I inhibitor
brain glioblastoma
PF-04691502Phase II
PI3-kinase class I inhibitor
endometrial cancer
PICTILISIBPhase II
PI3-kinase class I inhibitor
breast cancer
PILARALISIBPhase II
PI3-kinase class I inhibitor
PKI-179Phase I
PI3-kinase p110-alpha subunit inhibitor
neoplasm
RECILISIBPhase I
PI3-kinase class I inhibitor
SAMOTOLISIBPhase II
PI3-kinase class I inhibitor
prostate cancer
SERABELISIBPhase II
PI3-kinase p110-alpha subunit inhibitor
renal cell carcinoma
SF-1126Phase II
PI3-kinase class I inhibitor
head and neck malignant neoplasia
SONOLISIBPhase II
PI3-kinase class I inhibitor
TASELISIBPhase III
PI3-kinase class I inhibitor
breast cancer
VOXTALISIBPhase II
Serine/threonine-protein kinase mTOR inhibitor
VS-5584Phase I
Serine/threonine-protein kinase mTOR inhibitor
Malignant Mesothelioma
WX-037Phase I
PI3-kinase class I inhibitor
neoplasm
ZSTK-474Phase I
PI3-kinase class I inhibitor
Related Genes
AKT2Protein interaction100%ALKProtein interaction100%AXLProtein interaction100%BTKProtein interaction100%CBLBProtein interaction100%CD19Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
92%
Brain
72%
Lung
64%
Ovary
54%
Liver
32%
Gene Interaction Network
Click a node to explore
PIK3CAAKT2ALKAXLBTKCBLBCD19
PROTEIN STRUCTURE
Preparing viewer…
PDB9CMK · 1.75 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.22Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.12 [0.07–0.22]
RankingsWhere PIK3CA stands among ~20K protein-coding genes
  • #68of 20,598
    Most Researched1,720 · top 1%
  • #351of 1,025
    FDA-Approved Drug Targets4
  • #703of 5,498
    Most Pathogenic Variants111 · top quartile
  • #565of 17,882
    Most Constrained (LOEUF)0.22 · top 5%
Genes detectedPIK3CA
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
High frequency of mutations of the PIK3CA gene in human cancers.
PMID: 15016963
Science · 2004
1.00
2
PIK3CA, HRAS and KRAS gene mutations in human penile cancer.
PMID: 18355852
J Urol · 2008
0.92
3
PIK3CA gene aberrancy and role in targeted therapy of solid malignancies.
PMID: 31988478
Cancer Gene Ther · 2020
0.90
4
Aberrant PTEN, PIK3CA, pMAPK, and TP53 expression in human scalp and face angiosarcoma.
PMID: 34397726
Medicine (Baltimore) · 2021
0.82
5
Neddylation as a target in PIK3CA-mutated head and neck cancer.
PMID: 40154000
Biochem Biophys Res Commun · 2025
0.80