PIK3CA
Chr 3phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
Also known as: CCM4, CLAPO, CLOVE, CWS5, HMH, MCAP, MCM, MCMTC
Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]
Refuted — evidence has disproved this relationship
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
This gene — mechanism propensity
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
1609 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 6 | 46 | 0 | 0 | 52 |
Likely Pathogenic | 5 | 53 | 2 | 0 | 60 |
VUS | 20 | 605 | 32 | 5 | 662 |
Likely Benign | 2 | 6 | 147 | 559 | 714 |
Benign | 0 | 2 | 48 | 0 | 50 |
Conflicting | — | 25 | |||
| Total | 33 | 712 | 229 | 564 | 1,563 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →27 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap PIK3CA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
PIK3CA · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Newer Therapeutic Targets in Head and Neck Cancers
RECRUITINGTesting JNJ-42756493 (Erdafitinib) as Potentially Targeting Treatment in Cancers With FGFR Amplifications (MATCH-Subprotocol K1)
ACTIVE NOT RECRUITINGA Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer
RECRUITINGA Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors
ACTIVE NOT RECRUITINGA Study to Evaluate the Effectiveness and Safety of Inavolisib in Participants With Endocrine-resistant, PIK3CA-mutated, Hormone Receptor-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer
RECRUITINGOsimertinib and Etoposide as First-Line Treatment in Osimertinib-Resistant Advanced EGFR-Mutant NSCLC
NOT YET RECRUITINGRandomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer
ACTIVE NOT RECRUITINGInstitution of an Italian Registry and Biobank for Biological Sample Collection
RECRUITINGLevels of Circulating Tumor DNA as a Predictive Marker for Early Switch in Treatment for Patients With Metastatic (Stage IV) Breast Cancer
ACTIVE NOT RECRUITINGSerial Circulating Tumor DNA (ctDNA) Monitoring During Adjuvant Capecitabine in Early Triple-negative Breast Cancer
RECRUITINGSapanisertib and Serabelisib (PIKTOR) With Paclitaxel and a Substudy With an Insulin-Suppressing Diet in Patients With Advanced/Recurrent Endometrial Cancer
RECRUITINGPI3K Pathway Activation Markers in ER-Positive, HER2-Negative Breast Cancer: A Clinicopathologic Study
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools