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UniProtKB/Swiss-Prot P16234: Variant p.Val561Asp

Platelet-derived growth factor receptor alpha
Gene: PDGFRA
Chromosomal location: 4q11-q13
Variant information

Variant position:  561
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Aspartate (D) at position 561 (V561D, p.Val561Asp).
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 medium size and acidic (D)
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:  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:12522257, ECO:0000269|PubMed:15928335}. Note=The gene represented in this entry may be involved in disease pathogenesis. Mutations causing PDGFRA constitutive activation have been found in gastrointestinal stromal tumors lacking KIT mutations (PubMed:12522257). {ECO:0000269|PubMed:12522257}.
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 a GIST sample; constitutively activated kinase.
Any additional useful information about the variant.

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



Sequence information

Variant position:  561
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1089
The length of the canonical sequence.

Location on the sequence:   SLIVLVVIWKQKPRYEIRWR  V IESISPDGHEYIYVDPMQLP
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                         SLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLP

Mouse                         SLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLP

Rat                           SLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLP

Chicken                       SLIVLVIIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLP

Xenopus laevis                SLIVLVIIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLP

Zebrafish                     SLIVLVIIWKQKPRYEIRWRVIESVSPDGHEYIYVDPMQLP

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 24 – 1089 Platelet-derived growth factor receptor alpha
Topological domain 550 – 1089 Cytoplasmic
Modified residue 572 – 572 Phosphotyrosine; by autocatalysis
Modified residue 574 – 574 Phosphotyrosine; by autocatalysis
Alternative sequence 219 – 1089 Missing. In isoform 2.
Mutagenesis 572 – 572 Y -> F. Abolishes interaction with SRC-family members and impairs internalization of the activated receptor; when associated with F-574.
Mutagenesis 574 – 574 Y -> F. Abolishes interaction with SRC-family members and impairs internalization of the activated receptor; when associated with F-572.
Beta strand 560 – 565


Literature citations

PDGFRA activating mutations in gastrointestinal stromal tumors.
Heinrich M.C.; Corless C.L.; Duensing A.; McGreevey L.; Chen C.J.; Joseph N.; Singer S.; Griffith D.J.; Haley A.; Town A.; Demetri G.D.; Fletcher C.D.; Fletcher J.A.;
Science 299:708-710(2003)
Cited for: FUNCTION IN PHOSPHORYLATION OF AKT1; MAP KINASES; STAT1 AND STAT3; INVOLVEMENT IN GIST; VARIANTS ASP-561; VAL-842; 842-ASP--HIS-845 DEL AND 845-HIS--PRO-448 DEL; CHARACTERIZATION OF VARIANTS ASP-561; VAL-842; 842-ASP--HIS-845 DEL AND 845-HIS--PRO-448 DEL;

PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib.
Corless C.L.; Schroeder A.; Griffith D.; Town A.; McGreevey L.; Harrell P.; Shiraga S.; Bainbridge T.; Morich J.; Heinrich M.C.;
J. Clin. Oncol. 23:5357-5364(2005)
Cited for: INVOLVEMENT IN GIST; VARIANTS ASP-561; LYS-659; TYR-842; VAL-842; 842-ASP--HIS-845 DEL 845-HIS--PRO-448 DEL AND CYS-849; CHARACTERIZATION OF VARIANTS ASP-561; LYS-659; TYR-842; VAL-842; 842-ASP--HIS-845 DEL 845-HIS--PRO-448 DEL AND CYS-849; ACTIVITY REGULATION;

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.