UniProtKB/Swiss-Prot Q9NQ11: Variant p.Gly877Arg

Cation-transporting ATPase 13A2
Gene: ATP13A2
Chromosomal location: 1p36
Variant information

Variant position:  877
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 Glycine (G) to Arginine (R) at position 877 (G877R, p.Gly877Arg).
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 glycine (G) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Kufor-Rakeb syndrome (KRS) [MIM:606693]: A rare form of autosomal recessive juvenile or early-onset, levodopa-responsive parkinsonism. In addition to typical parkinsonian signs, clinical manifestations of Kufor-Rakeb syndrome include behavioral problems, facial tremor, pyramidal tract dysfunction, supranuclear gaze palsy, and dementia. {ECO:0000269|PubMed:16964263, ECO:0000269|PubMed:17485642, ECO:0000269|PubMed:18413573, ECO:0000269|PubMed:20683840, ECO:0000269|PubMed:20853184, ECO:0000269|PubMed:21542062, ECO:0000269|PubMed:22296644, ECO:0000269|PubMed:22388936, ECO:0000269|PubMed:22768177, ECO:0000269|PubMed:28137957}. Note=The disease is caused by mutations affecting the gene represented in this entry. KRS has also been referred to as neuronal ceroid lipofuscinosis 12 (CLN12), due to neuronal and glial lipofuscin deposits detected in the cortex, basal nuclei and cerebellum of some patients. {ECO:0000269|PubMed:22388936}.
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 KRS; found in two affected brothers also carrying C-481 in FBXO7; decreased protein stability; increased degradation by proteasome; novel location to endoplasmic reticulum.
Any additional useful information about the variant.

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

Sequence information

Variant position:  877
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1180
The length of the canonical sequence.

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.



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.

Chain 1 – 1180 Cation-transporting ATPase 13A2
Topological domain 481 – 932 Cytoplasmic
Metal binding 878 – 878 Magnesium
Metal binding 882 – 882 Magnesium

Literature citations

Novel ATP13A2 (PARK9) homozygous mutation in a family with marked phenotype variability.
Santoro L.; Breedveld G.J.; Manganelli F.; Iodice R.; Pisciotta C.; Nolano M.; Punzo F.; Quarantelli M.; Pappata S.; Di Fonzo A.; Oostra B.A.; Bonifati V.;
Neurogenetics 12:33-39(2011)
Cited for: VARIANT KRS ARG-877;

Common pathogenic effects of missense mutations in the P-type ATPase ATP13A2 (PARK9) associated with early-onset parkinsonism.
Podhajska A.; Musso A.; Trancikova A.; Stafa K.; Moser R.; Sonnay S.; Glauser L.; Moore D.J.;
PLoS ONE 7:E39942-E39942(2012)

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.