UniProtKB/Swiss-Prot P42336: Variant p.Glu542Lys

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Gene: PIK3CA
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Variant information Variant position:

542 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Glutamate (E) to Lysine (K) at position 542 (E542K, p.Glu542Lys). 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:

Change from medium size and acidic (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 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:

In CLOVE, KERSEB, CRC, BC, CLAPO, MADAC, CCM4 and HFMH; somatic mutation; also found in glioblastoma multiforme and endometrial carcinoma; somatic mutation; shows an increase in lipid kinase activity; oncogenic in vivo; occurs in the interface between the PI3K helical domain and the nSH2 (N-terminal SH2) region of the p85 regulatory subunit and may reduce the inhibitory effect of p85; requires interaction with RAS to induce cellular transformation; increased AKT and RPS6 phosphorylation in HFMH patient's cells. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121913273 [ dbSNP | Ensembl ]

Sequence information Variant position:

542 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1068 The length of the canonical sequence.
Location on the sequence:

ELRENDKEQLKAISTRDPLS E ITEQEKDFLWSHRHYCVTIP 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:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         ELRENDKEQLKAISTRDPLSEITEQEKDFLWSHRHYCVTIP

Mouse                         ELRENDKEQLRALCTRDPLSEITEQEKDFLWSHRHYCVTIP

Rat                           ELRENDKEQLRALCTRDPLSEITEQEKDFLWSHRHYCVTIP

Bovine                        ELRENDKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVTIP

Sequence annotation in neighborhood:

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.

Type	Positions	Description
Chain	1 – 1068	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Domain	517 – 694	PIK helical

Literature citations
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; CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype.
Rodriguez-Laguna L.; Ibanez K.; Gordo G.; Garcia-Minaur S.; Santos-Simarro F.; Agra N.; Vallespin E.; Fernandez-Montano V.E.; Martin-Arenas R.; Del Pozo A.; Gonzalez-Pecellin H.; Mena R.; Rueda-Arenas I.; Gomez M.V.; Villaverde C.; Bustamante A.; Ayuso C.; Ruiz-Perez V.L.; Nevado J.; Lapunzina P.; Lopez-Gutierrez J.C.; Martinez-Glez V.;
Genet. Med. 20:882-889(2018)
Cited for: INVOLVEMENT IN CLAPO; VARIANTS CLAPO SER-83; PRO-115; ARG-420; LYS-542 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; Hemifacial myohyperplasia is due to somatic muscular PIK3CA gain-of-function mutations and responds to pharmacological inhibition.
Bayard C.; Segna E.; Taverne M.; Fraissenon A.; Hennocq Q.; Periou B.; Zerbib L.; Ladraa S.; Chapelle C.; Hoguin C.; Kaltenbach S.; Villarese P.; Asnafi V.; Broissand C.; Nemazanyy I.; Autret G.; Goudin N.; Legendre C.; Authier F.J.; Viel T.; Tavitian B.; Gitiaux C.; Fraitag S.; Duong J.P.; Delcros C.; Sergent B.; Picard A.; Dussiot M.; Guibaud L.; Khonsari R.; Canaud G.;
J. Exp. Med. 220:0-0(2023)
Cited for: INVOLVEMENT IN HFMH; VARIANTS HFMH LYS-542; LYS-545 AND ARG-1047; CHARACTERIZATION OF VARIANTS HFMH LYS-542; LYS-545 AND ARG-1047; 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; PIK3CA mutations in glioblastoma multiforme.
Hartmann C.; Bartels G.; Gehlhaar C.; Holtkamp N.; von Deimling A.;
Acta Neuropathol. 109:639-642(2005)
Cited for: VARIANTS CANCER GLN-88; LYS-542; ALA-545 AND ASN-1025; 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 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 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.