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UniProtKB/Swiss-Prot P42336: Variant p.His1047Leu

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

Variant position:  1047
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Histidine (H) to Leucine (L) at position 1047 (H1047L, p.His1047Leu).
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 polar (H) to medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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

Involvement in disease:  Macrodactyly (MADAC) [MIM:155500]: A congenital anomaly characterized by fibrofatty tissue enlargement and bony overgrowth affecting the digits or the entire hand or foot. {ECO:0000269|PubMed:23100325}. Note=The disease may be caused by mutations affecting the gene represented in this entry. The tissue distribution of the clinical manifestations in MADAC seems to follow a pattern of somatic mosaicism. {ECO:0000269|PubMed:23100325}.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in disease:  CLAPO syndrome (CLAPO) [MIM:613089]: A syndrome characterized by capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry of face and limbs and partial or generalised overgrowth. {ECO:0000269|PubMed:29446767}. Note=The disease may be caused by mutations affecting the gene represented in this entry. The tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism. {ECO:0000269|PubMed:29446767}.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in disease:  Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:16353168}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In BC, CLAPO and MADAC; unknown pathological significance; somatic mutation in CLAPO patients.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  1047
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:   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: 
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:  
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 797 – 1068 PI3K/PI4K
Helix 1032 – 1047


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;

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;

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 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;

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.