PIK3CA Q546K

c.1636C>ANM_006218.33-179218306-C-A

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

Reports 2 in LM · GLA

ISSVA entity	Allele fraction	Sources
LM	not reported (LEC line; Sanger, not quantified)	PMID29985963
GLA	3.1-3.4% (LM tissue); 27.9% in isolated LM-LECs	PMID30591517

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

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 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 203 publications indexed by Europe PMC.