Variant position:  1047

Type of variant:  LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.]

Residue change:  From Histidine (H) to Arginine (R) at position 1047 (H1047R, p.His1047Arg).

Physico-chemical properties:  Change from medium size and polar (H) to large size and basic (R)

BLOSUM score:  0

Variant description:  In CLOVE, KERSEB, CRC, BC, OC, MADAC and CCM4; also found in an endometrial carcinoma sample; somatic mutation; shows an increase in lipid kinase activity; oncogenic in vivo; requires binding to p85 regulatory subunit to induce cellular transformation but not interaction with RAS; may mimic the conformatitonal change triggered by the interaction with RAS; enhances invadopodia-mediated extracellular matrix degradation and invasion in breast cancer cells; may alter the interaction of the PI3K/PI4K kinase domain with the cell membrane.

Other resources:  

• Variant rs121913279 [ dbSNP | Ensembl ]

Variant position:  1047

Protein sequence length:  1068

Location on the sequence:   ALDKTEQEALEYFMKQMNDA  H HGGWTTKMDWIFHTIKQHAL

Residue conservation: 

Human                         ALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHAL

Mouse                         ALDKTEQEALEYFTKQMNDAHHGGWTTKMDWIFHTIKQHAL

Rat                           ALDKTEQEALEYFTKQMNDAHHGGWTTKMDWIFHTIKQHAL

Bovine                        ALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHAL

Sequence annotation in neighborhood:  

Phosphoinositide 3-kinase signaling pathway mediated by p110{alpha} regulates invadopodia formation.
Yamaguchi H.; Yoshida S.; Muroi E.; Yoshida N.; Kawamura M.; Kouchi Z.; Nakamura Y.; Sakai R.; Fukami K.;
J. Cell Biol. 193:1275-1288(2011)
Cited for: FUNCTION IN INVADOPODIA FORMATION; CHARACTERIZATION OF VARIANTS LYS-545 AND ARG-1047;

Somatic gain-of-function mutations in PIK3CA in patients with macrodactyly.
Rios J.J.; Paria N.; Burns D.K.; Israel B.A.; Cornelia R.; Wise C.A.; Ezaki M.;
Hum. Mol. Genet. 22:444-451(2013)
Cited for: INVOLVEMENT IN MADAC; VARIANTS MADAC PRO-115; LYS-542; ARG-1047 AND LEU-1047;

Somatic PIK3CA mutations in sporadic cerebral cavernous malformations.
Peyre M.; Miyagishima D.; Bielle F.; Chapon F.; Sierant M.; Venot Q.; Lerond J.; Marijon P.; Abi-Jaoude S.; Le Van T.; Labreche K.; Houlston R.; Faisant M.; Clemenceau S.; Boch A.L.; Nouet A.; Carpentier A.; Boetto J.; Louvi A.; Kalamarides M.;
N. Engl. J. Med. 385:996-996(2021)
Cited for: INVOLVEMENT IN CCM4; VARIANTS CCM4 LYS-542; ARG-1047 AND LEU-1047;

A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane.
Mandelker D.; Gabelli S.B.; Schmidt-Kittler O.; Zhu J.; Cheong I.; Huang C.H.; Kinzler K.W.; Vogelstein B.; Amzel L.M.;
Proc. Natl. Acad. Sci. U.S.A. 106:16996-17001(2009)
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF MUTANT HIS-1047 IN COMPLEX WITH WORTMANNIN AND PIK3R1; INTERACTION WITH PIK3R1; CHARACTERIZATION OF VARIANT ARG-1047; DOMAINS;

Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas.
Broderick D.K.; Di C.; Parrett T.J.; Samuels Y.R.; Cummins J.M.; McLendon R.E.; Fults D.W.; Velculescu V.E.; Bigner D.D.; Yan H.;
Cancer Res. 64:5048-5050(2004)
Cited for: VARIANTS CANCER LYS-542; LYS-545; PRO-546; ASN-1021; ARG-1047; LEU-1047 AND TYR-1065;

Mutation of the PIK3CA gene in ovarian and breast cancer.
Campbell I.G.; Russell S.E.; Choong D.Y.H.; Montgomery K.G.; Ciavarella M.L.; Hooi C.S.F.; Cristiano B.E.; Pearson R.B.; Phillips W.A.;
Cancer Res. 64:7678-7681(2004)
Cited for: INVOLVEMENT IN OC; VARIANTS CANCER GLY-545; LYS-545; LYS-546; GLU-546; ARG-1047 AND LEU-1047;

High frequency of mutations of the PIK3CA gene in human cancers.
Samuels Y.; Wang Z.; Bardelli A.; Silliman N.; Ptak J.; Szabo S.; Yan H.; Gazdar A.; Powell S.M.; Riggins G.J.; Willson J.K.V.; Markowitz S.; Kinzler K.W.; Vogelstein B.; Velculescu V.E.;
Science 304:554-554(2004)
Cited for: VARIANT CANCER ARG-1047;

Mutations of PIK3CA in gastric adenocarcinoma.
Li V.S.W.; Wong C.W.; Chan T.L.; Chan A.S.W.; Zhao W.; Chu K.-M.; So S.; Chen X.; Yuen S.T.; Leung S.Y.;
BMC Cancer 5:29-29(2005)
Cited for: VARIANTS CANCER LYS-542; LYS-545 AND ARG-1047;

Functional analysis of PIK3CA gene mutations in human colorectal cancer.
Ikenoue T.; Kanai F.; Hikiba Y.; Obata T.; Tanaka Y.; Imamura J.; Ohta M.; Jazag A.; Guleng B.; Tateishi K.; Asaoka Y.; Matsumura M.; Kawabe T.; Omata M.;
Cancer Res. 65:4562-4567(2005)
Cited for: INVOLVEMENT IN CRC; CHARACTERIZATION OF VARIANTS CRC HIS-38; VAL-106; ARG-420; GLN-453; LYS-542; LYS-545; ILE-1043 AND ARG-1047;

High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma.
Oda K.; Stokoe D.; Taketani Y.; McCormick F.;
Cancer Res. 65:10669-10673(2005)
Cited for: VARIANTS CANCER GLN-542; LYS-542; GLY-545; LYS-545; ARG-1007; HIS-1021; CYS-1021; VAL-1035; ILE-1043; TYR-1047; ARG-1047; ASP-1050; LYS-1052 AND LEU-1065;

The prevalence of PIK3CA mutations in gastric and colon cancer.
Velho S.; Oliveira C.; Ferreira A.; Ferreira A.C.; Suriano G.; Schwartz S. Jr.; Duval A.; Carneiro F.; Machado J.C.; Hamelin R.; Seruca R.;
Eur. J. Cancer 41:1649-1654(2005)
Cited for: INVOLVEMENT IN CRC; VARIANTS CANCER LYS-542; GLY-545; LYS-545; GLN-1023; ARG-1047 AND LEU-1047;

PIK3CA mutations in advanced ovarian carcinomas.
Wang Y.; Helland A.; Holm R.; Kristensen G.B.; Boerresen-Dale A.-L.;
Hum. Mutat. 25:322-322(2005)
Cited for: VARIANTS CANCER LYS-545 AND ARG-1047;

PIK3CA mutations in head and neck squamous cell carcinoma.
Qiu W.; Schoenleben F.; Li X.; Ho D.J.; Close L.G.; Manolidis S.; Bennett B.P.; Su G.H.;
Clin. Cancer Res. 12:1441-1446(2006)
Cited for: VARIANTS CANCER CYS-343; LYS-542; LYS-545 AND ARG-1047; VARIANT MET-391;

PIK3CA mutations in nasopharyngeal carcinoma.
Or Y.Y.-Y.; Hui A.B.-Y.; To K.-F.; Lam C.N.-Y.; Lo K.-W.;
Int. J. Cancer 118:1065-1067(2006)
Cited for: VARIANT CANCER ARG-1047;

PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma.
Buttitta F.; Felicioni L.; Barassi F.; Martella C.; Paolizzi D.; Fresu G.; Salvatore S.; Cuccurullo F.; Mezzetti A.; Campani D.; Marchetti A.;
J. Pathol. 208:350-355(2006)
Cited for: VARIANTS BC LYS-542; VAL-542; LYS-545; ARG-546; ARG-1047 AND LEU-1047;

Cancer-specific mutations in PIK3CA are oncogenic in vivo.
Bader A.G.; Kang S.; Vogt P.K.;
Proc. Natl. Acad. Sci. U.S.A. 103:1475-1479(2006)
Cited for: CHARACTERIZATION OF VARIANTS CANCER LYS-542; LYS-545 AND ARG-1047;

Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern.
Hafner C.; Lopez-Knowles E.; Luis N.M.; Toll A.; Baselga E.; Fernandez-Casado A.; Hernandez S.; Ribe A.; Mentzel T.; Stoehr R.; Hofstaedter F.; Landthaler M.; Vogt T.; Pujol R.M.; Hartmann A.; Real F.X.;
Proc. Natl. Acad. Sci. U.S.A. 104:13450-13454(2007)
Cited for: VARIANTS KERSEB LYS-542; LYS-545; GLY-545 AND ARG-1047;

Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome.
Kurek K.C.; Luks V.L.; Ayturk U.M.; Alomari A.I.; Fishman S.J.; Spencer S.A.; Mulliken J.B.; Bowen M.E.; Yamamoto G.L.; Kozakewich H.P.; Warman M.L.;
Am. J. Hum. Genet. 90:1108-1115(2012)
Cited for: VARIANTS CLOVE ARG-420; LYS-542 AND ARG-1047;