PIK3CA Q546K

c.1636C>A NM_006218.3 PI3K-AKT transversion, gain of function

Cancer hotspot Recurrent missense variant. COSMIC COSV55873527, COSV55882350

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

ClinVar Pathogenic VCV000013657

Protein region PIK helical Residue 546 of PIK3CA. UniProt P42336

AlphaMissense likely pathogenic Pathogenicity score 0.90. Computational prediction, not clinical evidence.

Position in PIK3CA 14 catalogued

Reported in LM · GLA

ISSVA subset	Allele fraction	Sources
LM	1.1-23%	PMC6037383
GLA	1.1-23%	PMC6363432

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 (2)

Somatic activating mutations in PIK3CA cause generalized lymphatic anomaly.
Rodriguez-Laguna L, Agra N, Ibañez K, Ibañez K, Oliva-Molina G, Gordo G, Khurana N, Hominick D, Beato M, Colmenero I, Herranz G, Torres Canizalez JM, Rodríguez Pena R, Vallespín E, Martín-Arenas R, Del Pozo Á, Villaverde C, Bustamante A, Ayuso C, Lapunzina P, Lopez-Gutierrez JC, Dellinger MT, Martinez-Glez V. · J Exp Med · 2019
PIK3CA mutations are specifically localized to lymphatic endothelial cells of lymphatic malformations.
Blesinger H, Kaulfuß S, Aung T, Schwoch S, Prantl L, Rößler J, Wilting J, Becker J. · PLoS One · 2018

Mentioned in 200 publications indexed by Europe PMC.

Cross-references

COSMIC COSV55873527 COSMIC COSV55882350 rs121913286 gnomAD · PIK3CA ClinVar · Q546K OncoKB cBioPortal · PIK3CA VarSome UniProt · PIK3CA AlphaFold · PIK3CA