PIK3CA N345K

c.1035T>A NM_006218.3 PI3K-AKT transversion, gain of function

Cancer hotspot Recurrent missense variant. COSMIC COSV55873276

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

ClinVar Pathogenic VCV000376050

Protein region C2 PI3K-type Residue 345 of PIK3CA. UniProt P42336

AlphaMissense likely pathogenic Pathogenicity score 1.00. Computational prediction, not clinical evidence.

Position in PIK3CA 14 catalogued

Reported in LM

ISSVA subset	Allele fraction	Sources
LM	<=1.4%	PMC8972000

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)

Somatic activating BRAF variants cause isolated lymphatic malformations.
Zenner K, Jensen DM, Dmyterko V, Shivaram GM, Myers CT, Paschal CR, Rudzinski ER, Pham MM, Cheng VC, Manning SC, Bly RA, Ganti S, Perkins JA, Bennett JT. · HGG Adv · 2022

Mentioned in 258 publications indexed by Europe PMC.

Cross-references

COSMIC COSV55873276 rs121913284 gnomAD · PIK3CA ClinVar · N345K OncoKB cBioPortal · PIK3CA VarSome UniProt · PIK3CA AlphaFold · PIK3CA