PIK3CA E545A

c.1634A>CNM_006218.33-179218304-A-C

PI3K-AKT gain of function transversion Cancer hotspot Absent from gnomAD ClinVar: Pathogenic AlphaMissense: likely pathogenic LM

Reports 1 in LM

ISSVA entity	Allele fraction	Sources
LM	not reported (LEC line; direct sequencing)	PMID25292196

Position in PIK3CA 16 catalogued variants in this gene

Pathway and targeted therapy

Variant in the PI3K-AKT pathway. Repurposed drugs already used in the clinic for this pathway: alpelisib (PI3Kα inhibitor), sirolimus (mTOR inhibitor).

Open and recent trials (4 in vascular / lymphatic anomalies for alpelisib)

A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations RECRUITING NCT05983159 · PHASE2 · WHO ICTRP
24VA022; VATCH Alpelisib for TIE2/PIK3CA Pathway VAs ACTIVE NOT RECRUITING NCT07543822 · PHASE2 · WHO ICTRP
Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation. RECRUITING NCT05948943 · PHASE2, PHASE3 · WHO ICTRP
A Study of Clinical Practice and Real-world Care of Patients Treated With mTOR, PI3K, and MEK Inhibitors for Extracranial Vascular Anomalies NOT YET RECRUITING NCT07767877 · WHO ICTRP

Primary sources 1

Activating PIK3CA alleles and lymphangiogenic phenotype of lymphatic endothelial cells isolated from lymphatic malformations.
Osborn AJ, Dickie P, Neilson DE, Glaser K, Lynch KA, Gupta A, Dickie BH. · Hum Mol Genet · 2015

Mentioned in 245 publications indexed by Europe PMC.