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Gene | PIK3CA |
Variant | H1047L |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | PIK3CA H1047L is a hotspot mutation that lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). H1047L results in increased phosphorylation of Akt and Mek1/2, growth factor-independent cell survival, and transformation in cell culture (PMID: 26627007, PMID: 29533785). |
Associated Drug Resistance | |
Category Variants Paths |
PIK3CA mutant PIK3CA act mut PIK3CA H1047L PIK3CA mutant PIK3CA exon21 PIK3CA H1047X PIK3CA H1047L |
Transcript | NM_006218.4 |
gDNA | chr3:g.179234297A>T |
cDNA | c.3140A>T |
Protein | p.H1047L |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_006713658.5 | chr3:g.179234297A>T | c.3140A>T | p.H1047L | RefSeq | GRCh38/hg38 |
XM_006713658 | chr3:g.179234297A>T | c.3140A>T | p.H1047L | RefSeq | GRCh38/hg38 |
XM_006713658.4 | chr3:g.179234297A>T | c.3140A>T | p.H1047L | RefSeq | GRCh38/hg38 |
XM_011512894 | chr3:g.179234297A>T | c.3140A>T | p.H1047L | RefSeq | GRCh38/hg38 |
NM_006218.4 | chr3:g.179234297A>T | c.3140A>T | p.H1047L | RefSeq | GRCh38/hg38 |
NM_006218.3 | chr3:g.179234297A>T | c.3140A>T | p.H1047L | RefSeq | GRCh38/hg38 |
NM_006218 | chr3:g.179234297A>T | c.3140A>T | p.H1047L | RefSeq | GRCh38/hg38 |
XM_011512894.2 | chr3:g.179234297A>T | c.3140A>T | p.H1047L | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
PIK3CA H1047L | breast cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047L | breast cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047L | breast cancer | sensitive | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, Alpelisib (BYL719) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047L | breast cancer | sensitive | Lapatinib | Preclinical | Actionable | In a preclinical study, Tykerb (lapatinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047L | breast cancer | sensitive | MK2206 | Preclinical | Actionable | In a preclinical study, MK2206 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047L | breast cancer | sensitive | Neratinib | Preclinical | Actionable | In a preclinical study, Nerlynx (neratinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA H1047L in culture (PMID: 26627007). | 26627007 |
PIK3CA H1047L | oral squamous cell carcinoma | decreased response | Palbociclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with Ibrance (palbociclib) resulted in sustained tumor growth, but increasing tumor volume over time with treatment in oral squamous cell carcinoma cell line xenograft models harboring PIK3CA H1047L (PMID: 31516747). | 31516747 |
PIK3CA H1047L | oral squamous cell carcinoma | predicted - sensitive | PF-04691502 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PF-04691502 treatment inhibited tumor growth in a cell line xenograft model of oral squamous cell carcinoma harboring PIK3CA H1047L (PMID: 31516747). | 31516747 |
PIK3CA H1047L | oral squamous cell carcinoma | sensitive | Palbociclib + PF-04691502 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, oral squamous cell carcinoma cells harboring PIK3CA H1047L demonstrated increased sensitivity to Ibrance (palbociclib) when combined with PF-04691502, and the combination treatment inhibited proliferation in cell culture, and reduced tumor growth in a cell line xenograft model (PMID: 31516747). | 31516747 |
PIK3CA H1047L | colon cancer | sensitive | STX-478 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, STX-478 inhibited viability in a colon cancer cell line harboring PIK3CA H1047L in culture, and inhibited tumor growth and induced tumor regression in a cell line xenograft model (PMID: 37623743). | 37623743 |
PIK3CA H1047L | Her2-receptor negative breast cancer | predicted - sensitive | HS-10352 | Case Reports/Case Series | Actionable | In a Phase I trial, HS-10352 treatment resulted in an objective response rate (ORR) of 27.8% (5/18, all partial responses), disease control rate (DCR) of 55.6%, and median progression-free survival (mPFS) of 3.9 mo in HR-positive, ERBB2 (HER2)-negative advanced breast cancer patients overall, and in the 6mg group led to an ORR of 66.7% and DCR of 83.3%, with an ORR of 75.0% (3/4) and DCR of 100% in patients with PIK3CA mutations (E542K, E545K, E545D, H1047L, H1047R) (PMID: 38037839; NCT04631835). | 38037839 |