PIK3CA E545G

c.1634A>G NM_006218.3 PI3K-AKT transition, gain of function

Cancer hotspot Recurrent missense variant. COSMIC COSV55873209, COSV55873220, COSV55892885

Population · gnomAD Not observed Absent from the population database, consistent with a somatic, non-inherited driver.

ClinVar Pathogenic VCV000013656

Protein region PIK helical Residue 545 of PIK3CA. UniProt P42336

AlphaMissense likely pathogenic Pathogenicity score 0.95. Computational prediction, not clinical evidence.

Position in PIK3CA 14 catalogued

Reported in LM

ISSVA subset	Allele fraction	Sources
LM	6.55-10.01%	PMC8194016

Bars show the reported allele-fraction range on a 0 to 50 percent axis.

Pathway and targeted therapy

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

Open and recent trials (3 in vascular / lymphatic anomalies for alpelisib)

Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation. RECRUITING NCT05948943 · PHASE2, PHASE3
A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations RECRUITING NCT05983159 · PHASE2
24VA022; VATCH Alpelisib for TIE2/PIK3CA Pathway VAs ACTIVE NOT RECRUITING NCT07543822 · PHASE2

Primary sources (1)

Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations.
Brouillard P, Schlögel MJ, Homayun Sepehr N, Helaers R, Queisser A, Fastré E, Boutry S, Schmitz S, Clapuyt P, Hammer F, Dompmartin A, Weitz-Tuoretmaa A, Laranne J, Pasquesoone L, Vilain C, Boon LM, Vikkula M. · Orphanet J Rare Dis · 2021

Mentioned in 208 publications indexed by Europe PMC.

Cross-references

COSMIC COSV55873209 COSMIC COSV55873220 COSMIC COSV55892885 rs121913274 gnomAD · PIK3CA ClinVar · E545G OncoKB cBioPortal · PIK3CA VarSome UniProt · PIK3CA AlphaFold · PIK3CA