PIK3CA H1047R

c.3140A>G NM_006218.3 PI3K-AKT transition, gain of function

Cancer hotspot Recurrent missense variant. COSMIC COSV55873195, COSV55873401, COSV55888015

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

ClinVar Pathogenic VCV000013652

Protein region PI3K/PI4K catalytic Residue 1047 of PIK3CA. UniProt P42336

AlphaMissense ambiguous Pathogenicity score 0.54. Computational prediction, not clinical evidence.

Position in PIK3CA 14 catalogued

Reported in LM · GLA · KLA · CCLA

ISSVA subset	Allele fraction	Sources
LM	3.9-11%	PMC8972000
GLA	3.9-11%	PMC6363432
KLA	0.41%	PMC11184491
CCLA	0.88%	PMC11184491

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 (3)

Genomic profiling informs diagnoses and treatment in vascular anomalies.
Li D, Sheppard SE, March ME, Battig MR, Surrey LF, Srinivasan AS, Matsuoka LS, Tian L, Wang F, Seiler C, Dayneka J, Borst AJ, Matos MC, Paulissen SM, Krishnamurthy G, Nriagu B, Sikder T, Casey M, Williams L, Rangu S, O'Connor N, Thomas A, Pinto E, Hou C, Nguyen K, Pellegrino da Silva R, Chehimi SN, Kao C, Biroc L, Britt AD, Queenan M, Reid JR, Napoli JA, Low DM, Vatsky S, Treat J, Smith CL, Cahill AM, Snyder KM, Adams DM, Dori Y, Hakonarson H. · Nat Med · 2023
Somatic activating BRAF variants cause isolated lymphatic malformations.
Zenner K, Jensen DM, Dmyterko V, Shivaram GM, Myers CT, Paschal CR, Rudzinski ER, Pham MM, Cheng VC, Manning SC, Bly RA, Ganti S, Perkins JA, Bennett JT. · HGG Adv · 2022
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

Mentioned in 3,129 publications indexed by Europe PMC.

Cross-references

COSMIC COSV55873195 COSMIC COSV55873401 COSMIC COSV55888015 rs121913279 gnomAD · PIK3CA ClinVar · H1047R OncoKB cBioPortal · PIK3CA VarSome UniProt · PIK3CA AlphaFold · PIK3CA