UniProtKB/Swiss-Prot Q99959: Variant p.Cys796Arg

Plakophilin-2
Gene: PKP2
Chromosomal location: 12p11
Variant information

Variant position:  796
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 Cysteine (C) to Arginine (R) at position 796 (C796R, p.Cys796Arg).
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:  Arrhythmogenic right ventricular dysplasia, familial, 9 (ARVD9) [MIM:609040]: A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. 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 ARVD9; impairs protein stability.
Any additional useful information about the variant.



Sequence information

Variant position:  796
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  881
The length of the canonical sequence.

Location on the sequence:   SIIPDTVPSTDLLIETTASA  C YTLNNIIQNSYQNARDLLNT
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.

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 – 881 Plakophilin-2
Repeat 763 – 804 ARM 7


Literature citations

Molecular insights into arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 missense mutations.
Kirchner F.; Schuetz A.; Boldt L.H.; Martens K.; Dittmar G.; Haverkamp W.; Thierfelder L.; Heinemann U.; Gerull B.;
Circ. Cardiovasc. Genet. 5:400-411(2012)
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 346-620 OF VARIANT ARVD9 ARG-796; VARIANT ARVD9 ARG-796; CHARACTERIZATION OF VARIANTS ARVD9 PHE-615; GLN-654 AND ARG-796; FUNCTION; INTERACTION WITH JUP AND DSP; SUBCELLULAR LOCATION; TISSUE SPECIFICITY;

Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy.
Gerull B.; Heuser A.; Wichter T.; Paul M.; Basson C.T.; McDermott D.A.; Lerman B.B.; Markowitz S.M.; Ellinor P.T.; MacRae C.A.; Peters S.; Grossmann K.S.; Michely B.; Sasse-Klaassen S.; Birchmeier W.; Dietz R.; Breithardt G.; Schulze-Bahr E.; Thierfelder L.;
Nat. Genet. 36:1162-1164(2004)
Cited for: VARIANTS ARVD9 PHE-140; PHE-615; GLN-654 AND ARG-796;

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.