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PIK3CA E453K - Gene Variant Detail

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Gene PIK3CA
Variant E453K
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions PIK3CA E453K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E453K results in increased phosphorylation of Akt and Mek1/2, enhanced cell survival, increased cell proliferation and migration, and is transforming in culture (PMID: 26627007, PMID: 29533785, PMID: 34779417).
Associated Drug Resistance
Category Variants Paths

PIK3CA mutant PIK3CA act mut PIK3CA E453K

PIK3CA mutant PIK3CA exon8 PIK3CA E453K

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Transcript NM_006218.4
gDNA chr3:g.179210291G>A
cDNA c.1357G>A
Protein p.E453K
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_011512894 chr3:g.179210291G>A c.1357G>A p.E453K RefSeq GRCh38/hg38
XM_006713658.5 chr3:g.179210291G>A c.1357G>A p.E453K RefSeq GRCh38/hg38
NM_006218.3 chr3:g.179210291G>A c.1357G>A p.E453K RefSeq GRCh38/hg38
XM_006713658 chr3:g.179210291G>A c.1357G>A p.E453K RefSeq GRCh38/hg38
XM_006713658.4 chr3:g.179210291G>A c.1357G>A p.E453K RefSeq GRCh38/hg38
XM_011512894.2 chr3:g.179210291G>A c.1357G>A p.E453K RefSeq GRCh38/hg38
NM_006218.4 chr3:g.179210291G>A c.1357G>A p.E453K RefSeq GRCh38/hg38
NM_006218 chr3:g.179210291G>A c.1357G>A p.E453K RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PIK3CA E453K breast cancer resistant Buparlisib Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells expressing PIK3CA E453K demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477). 29636477
PIK3CA E453K lung squamous cell carcinoma no benefit Taselisib Case Reports/Case Series Actionable In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in no response in a patient harboring PIK3CA E453K (PMID: 31158500; NCT02785913). 31158500