UniProtKB/Swiss-Prot P09619: Variant p.Arg561Cys

Platelet-derived growth factor receptor beta
Gene: PDGFRB
Chromosomal location: 5q31-q32
Variant information

Variant position:  561
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Cysteine (C) at position 561 (R561C, p.Arg561Cys).
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 large size and basic (R) to medium size and polar (C)
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:  Myofibromatosis, infantile 1 (IMF1) [MIM:228550]: A rare mesenchymal disorder characterized by the development of benign tumors in the skin, striated muscles, bones, and, more rarely, visceral organs. Subcutaneous or soft tissue nodules commonly involve the skin of the head, neck, and trunk. Skeletal and muscular lesions occur in about half of the patients. Lesions may be solitary or multicentric, and they may be present at birth or become apparent in early infancy or occasionally in adult life. Visceral lesions are associated with high morbidity and mortality. 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.

Variant description:  In IMF1.
Any additional useful information about the variant.



Sequence information

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

Protein sequence length:  1106
The length of the canonical sequence.

Location on the sequence:   LVVLTIISLIILIMLWQKKP  R YEIRWKVIESVSSDGHEYIY
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                         LVVLTIISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIY

Mouse                         LVVLTVISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIY

Rat                           LVVLTVISLIILIMLWQRKPRYEIRWKVIESVSSDGHEYIY

Dog                           LVVLTIISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIY

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 33 – 1106 Platelet-derived growth factor receptor beta
Topological domain 554 – 1106 Cytoplasmic
Modified residue 562 – 562 Phosphotyrosine; by autocatalysis
Modified residue 579 – 579 Phosphotyrosine; by autocatalysis
Modified residue 581 – 581 Phosphotyrosine; by autocatalysis
Mutagenesis 579 – 579 Y -> F. Loss of kinase activity; when associated with F-581. Strongly reduces interaction with SRC family kinases. No effect on interaction with GRB10.
Mutagenesis 581 – 581 Y -> F. Loss of kinase activity; when associated with F-579. No effect on interaction with GRB10.


Literature citations

A recurrent PDGFRB mutation causes familial infantile myofibromatosis.
Cheung Y.H.; Gayden T.; Campeau P.M.; Leduc C.A.; Russo D.; Nguyen V.H.; Guo J.; Qi M.; Guan Y.; Albrecht S.; Moroz B.; Eldin K.W.; Lu J.T.; Schwartzentruber J.; Malkin D.; Berghuis A.M.; Emil S.; Gibbs R.A.; Burk D.L.; Vanstone M.; Lee B.H.; Orchard D.; Boycott K.M.; Chung W.K.; Jabado N.;
Am. J. Hum. Genet. 92:996-1000(2013)
Cited for: VARIANT IMF1 CYS-561;

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.