Home  |  Contact

UniProtKB/Swiss-Prot P10721: Variant p.Val559Ala

Mast/stem cell growth factor receptor Kit
Gene: KIT
Variant information

Variant position:  559
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
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 Valine (V) to Alanine (A) at position 559 (V559A, p.Val559Ala).
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 hydrophobic (V) to small size and hydrophobic (A)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  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

Involvement in disease:  Gastrointestinal stromal tumor (GIST) [MIM:606764]: Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery. {ECO:0000269|PubMed:11505412, ECO:0000269|PubMed:15824741, ECO:0000269|PubMed:9438854, ECO:0000269|PubMed:9697690}. Note=The gene represented in this entry is 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.

Variant description:  In GIST.
Any additional useful information about the variant.

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

Sequence information

Variant position:  559
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  976
The length of the canonical sequence.

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.










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.

Chain 26 – 976 Mast/stem cell growth factor receptor Kit
Topological domain 546 – 976 Cytoplasmic
Metal binding 568 – 568 Magnesium
Modified residue 547 – 547 Phosphotyrosine; by autocatalysis
Modified residue 553 – 553 Phosphotyrosine; by autocatalysis
Modified residue 568 – 568 Phosphotyrosine; by autocatalysis
Modified residue 570 – 570 Phosphotyrosine; by autocatalysis
Alternative sequence 414 – 976 Missing. In isoform 3.
Mutagenesis 571 – 571 I -> A. Reduction in SH2B2/APS binding. Abolishes SH2B2/APS binding; when associated with A-939.
Beta strand 558 – 564

Literature citations

Germline mutation in the juxtamembrane domain of the kit gene in a family with gastrointestinal stromal tumors and urticaria pigmentosa.
Beghini A.; Tibiletti M.G.; Roversi G.; Chiaravalli A.M.; Serio G.; Capella C.; Larizza L.;
Cancer 92:657-662(2001)
Cited for: VARIANT GIST ALA-559;

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.