Gene Variant Detail

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Gene PIK3CA
Variant P449T
Impact List missense
Protein Effect gain of function - predicted
Gene Variant Descriptions PIK3CA P449T lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P449T results in increased Pik3ca kinase activity in cell culture (PMID: 20530683), and therefore, is predicted to result in a gain of Pik3ca protein function.
Associated Drug Resistance
Category Variants Paths

PIK3CA mutant PIK3CA exon8 PIK3CA P449T

PIK3CA mutant PIK3CA act mut PIK3CA P449T

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Transcript NM_006218.3
gDNA chr3:g.179210279C>A
cDNA c.1345C>A
Protein p.P449T
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_006713658.4 chr3:g.179210279C>A c.1345C>A p.P449T RefSeq GRCh38/hg38
NM_006218 chr3:g.179210279C>A c.1345C>A p.P449T RefSeq GRCh38/hg38
XM_011512894 chr3:g.179210279C>A c.1345C>A p.P449T RefSeq GRCh38/hg38
XM_011512894.2 chr3:g.179210279C>A c.1345C>A p.P449T RefSeq GRCh38/hg38
NM_006218.3 chr3:g.179210279C>A c.1345C>A p.P449T RefSeq GRCh38/hg38
XM_006713658 chr3:g.179210279C>A c.1345C>A p.P449T RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E PIK3CA P449T colorectal cancer resistant Cetuximab Preclinical Actionable In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Erbitux (cetuximab) in culture (PMID: 25838391). 25838391
BRAF V600E PIK3CA P449T colorectal cancer resistant Regorafenib Preclinical Actionable In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). 25838391
BRAF V600E PIK3CA P449T colorectal cancer sensitive Cetuximab + Regorafenib Preclinical Actionable In a preclinical study, the combination of Erbitux (cetuximab) and Stivarga (regorafenib) inhibited growth, reduced Akt and Mapk phosphorylation, and induced apoptosis of human colorectal cancer cell lines harboring BRAF V600E and PIK3CA P449T in culture (PMID: 25838391). 25838391
BRAF V600E PIK3CA P449T colorectal cancer sensitive Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
BRAF V600E PIK3CA P449T colorectal cancer sensitive Everolimus + Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
BRAF V600E PIK3CA P449T colorectal cancer sensitive Pimasertib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
BRAF V600E PIK3CA P449T colorectal cancer sensitive Pimasertib + Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
BRAF V600E PIK3CA P449T TP53 R273H colorectal cancer sensitive PD-0325901 + Sapanisertib Preclinical - Cell line xenograft Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and growth of colorectal cancer cells harboring BRAF V600E, PIK3CA P449T, and TP53 R273H in culture and in cell line xenograft models, but did not have synergistic effect on apoptosis (PMID: 26272063). 26272063