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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P42336: Variant p.His1047Arg

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Gene: PIK3CA
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Variant information Variant position: help 1047 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change: help From Histidine (H) to Arginine (R) at position 1047 (H1047R, p.His1047Arg). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from medium size and polar (H) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description: help 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. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1047 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1068 The length of the canonical sequence.
Location on the sequence: help ALDKTEQEALEYFMKQMNDA H HGGWTTKMDWIFHTIKQHAL The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         ALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHAL

Mouse                         ALDKTEQEALEYFTKQMNDAHHGGWTTKMDWIFHTIKQHAL

Rat                           ALDKTEQEALEYFTKQMNDAHHGGWTTKMDWIFHTIKQHAL

Bovine                        ALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHAL

Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 1068 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Domain 765 – 1051 PI3K/PI4K catalytic
Helix 1032 – 1047



Literature citations
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;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.