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UniProtKB/Swiss-Prot P42336: Variant p.Cys420Arg

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

Variant position:  420
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 Cysteine (C) to Arginine (R) at position 420 (C420R, p.Cys420Arg).
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 (C) to large size and basic (R)
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:  Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:15930273, ECO:0000269|PubMed:15994075}. Note=The gene represented in this entry may be involved in disease pathogenesis.
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:  Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) [MIM:612918]: A sporadically occurring, non-hereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. It is defined by four main clinical findings: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities. The presence of truncal overgrowth and characteristic patterned macrodactyly at birth differentiates CLOVE from other syndromic forms of overgrowth. {ECO:0000269|PubMed:22658544}. Note=The disease is caused by mutations 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.

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.

Variant description:  In CLOVE, CRC and CLAPO; unknown pathological significance; somatic mutation in CLAPO patients; shows an increase in lipid kinase activity; may increase the affinity for lipid membranes.
Any additional useful information about the variant.

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



Sequence information

Variant position:  420
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:   ARLCLSICSVKGRKGAKEEH  C PLAWGNINLFDYTDTLVSGK
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                         ARLCLSICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGK

Mouse                         ARLCLSICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGK

Rat                           ARLCLSICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGK

Bovine                        ARLCLSICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGK

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 330 – 487 C2 PI3K-type
Beta strand 416 – 430


Literature citations

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;

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;

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.