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UniProtKB/Swiss-Prot O15484: Variant p.Leu244Pro

Calpain-5
Gene: CAPN5
Variant information

Variant position:  244
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 Leucine (L) to Proline (P) at position 244 (L244P, p.Leu244Pro).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Vitreoretinopathy, neovascular inflammatory (VRNI) [MIM:193235]: An autoimmune condition of the eye that sequentially mimics uveitis, retinitis pigmentosa, and proliferative diabetic retinopathy as it progresses to complete blindness. Patients present during the second or third decade of life with posterior uveitis and reduction of the electroretinogram b-wave. They become more symptomatic when cataracts, cystoid macular edema, and disk edema diminish visual acuity during the second stage. Severe vision loss begins during the third stage when proliferative retinal neovascularization and epiretinal membranes appear. There is an ongoing pigmentary retinal degeneration and peripheral visual field loss during all stages. In the fourth stage, proliferative vitreoretinopathy causes tractional retinal detachments at the macula and vitreous base. The fifth or end-stage disease is marked by phthisis. {ECO:0000269|PubMed:23055945}. 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 VRNI; largely mislocalized to the cytoplasm whereas the wild-type protein is localized near the cell surface.
Any additional useful information about the variant.

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



Sequence information

Variant position:  244
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  640
The length of the canonical sequence.

Location on the sequence:   RGGLISASIKAVTAADMEAR  L ACGLVKGHAYAVTDVRKVRL
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                         RGGLISASIKAVTAADMEARLACGLVKGHAYAVTDVRKVRL

Mouse                         RGGLISASIKAVTAADMEARLACGLVKGHAYAVTDVRKVRL

Rat                           RGGLISASIKAMTAADMETRLACGLVKGHAYAVTDVRKVRL

Caenorhabditis elegans        KGALVVAAIAARTKEEIEESLDCGLVKGHAYAVSAVCTIDV

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 – 640 Calpain-5
Domain 26 – 343 Calpain catalytic
Active site 252 – 252


Literature citations

Calpain-5 mutations cause autoimmune uveitis, retinal neovascularization, and photoreceptor degeneration.
Mahajan V.B.; Skeie J.M.; Bassuk A.G.; Fingert J.H.; Braun T.A.; Daggett H.T.; Folk J.C.; Sheffield V.C.; Stone E.M.;
PLoS Genet. 8:E1003001-E1003001(2012)
Cited for: TISSUE SPECIFICITY; VARIANTS VRNI LEU-243 AND PRO-244; CHARACTERIZATION OF VARIANTS VRNI LEU-243 AND PRO-244;

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.