UniProtKB/Swiss-Prot P56539: Variant p.Ala46Val

Caveolin-3
Gene: CAV3
Chromosomal location: 3p25
Variant information

Variant position:  46
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 Alanine (A) to Valine (V) at position 46 (A46V, p.Ala46Val).
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 small size and hydrophobic (A) to medium size and hydrophobic (V)
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:  Rippling muscle disease (RMD) [MIM:606072]: Rare disorder characterized by mechanically triggered contractions of skeletal muscle. In RMD, mechanical stimulation leads to electrically silent muscle contractions that spread to neighboring fibers that cause visible ripples to move over the muscle. 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 RMD.
Any additional useful information about the variant.



Sequence information

Variant position:  46
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  151
The length of the canonical sequence.

Location on the sequence:   NRDPKNINEDIVKVDFEDVI  A EPVGTYSFDGVWKVSYTTFT
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                         NRDPKNINEDIVKVDFEDVIAEPVGTYSFDGVWKVSYTTFT

Mouse                         NRDPKNINEDIVKVDFEDVIAEPEGTYSFDGVWKVSFTTFT

Rat                           NRDPKNINEDIVKVDFEDVIAEPEGTYSFDGVWRVSYTTFT

Pig                           NRDPKNINEDIVKVDFEDVIAEPVGTYSFDGVWKVSYTTFT

Bovine                        NRDPKNINEDIVKVDFEDVIAEPVGTYSFDGVWKVSYTTFT

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 – 151 Caveolin-3
Topological domain 1 – 83 Cytoplasmic
Cross 38 – 38 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO3)


Literature citations

Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease.
Betz R.C.; Schoser B.G.H.; Kasper D.; Ricker K.; Ramirez A.; Stein V.; Torbergsen T.; Lee Y.-A.; Nothen M.M.; Wienker T.F.; Malin J.-P.; Propping P.; Reis A.; Mortier W.; Jentsch T.J.; Vorgerd M.; Kubisch C.;
Nat. Genet. 28:218-219(2001)
Cited for: VARIANTS RMD GLN-27; THR-46; VAL-46 AND LEU-105; SURFACE EXPRESSION OF VARIANT RMD THR-46;

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.