UniProtKB/SwissProt variant VAR

Variant information

Variant position:

12

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

Type of variant:

LP/P [Disclaimer]

The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Threonine (T) to Methionine (M) at position 12 (T12M, p.Thr12Met).

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 (T) to medium size and hydrophobic (M)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-1

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

Variant description:

In KRS; no effect on stability; no effect on location; decreased ATPase activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs151117874 [ dbSNP | Ensembl ]

Sequence information

Variant position:

12

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

Protein sequence length:

1180

The length of the canonical sequence.

Location on the sequence:

MSADSSPLVGS T PTGYGTLTIGTSIDPLSSSV

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                         MSADSSPLVGSTPTGYGTLTIGTSIDPLSSSV

Mouse                         MSADSSLLMGSTPPSYGTLTTGTSIDPLSSSA

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.

Type	Positions	Description
Chain	1 – 1180	Polyamine-transporting ATPase 13A2
Topological domain	1 – 44	Cytoplasmic

Literature citations

ATP13A2 deficiency disrupts lysosomal polyamine export.
van Veen S.; Martin S.; Van den Haute C.; Benoy V.; Lyons J.; Vanhoutte R.; Kahler J.P.; Decuypere J.P.; Gelders G.; Lambie E.; Zielich J.; Swinnen J.V.; Annaert W.; Agostinis P.; Ghesquiere B.; Verhelst S.; Baekelandt V.; Eggermont J.; Vangheluwe P.;
Nature 578:419-424(2020)
Cited for: FUNCTION; CATALYTIC ACTIVITY; ACTIVITY REGULATION; BIOPHYSICOCHEMICAL PROPERTIES; CHARACTERIZATION OF VARIANTS KRS MET-12; ARG-533; THR-746 AND ARG-877; CHARACTERIZATION OF VARIANT SPG8 ILE-517; MUTAGENESIS OF GLU-348; ALA-472; ASP-513; ASP-967 AND LYS-1067;

ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease.
Di Fonzo A.; Chien H.F.; Socal M.; Giraudo S.; Tassorelli C.; Iliceto G.; Fabbrini G.; Marconi R.; Fincati E.; Abbruzzese G.; Marini P.; Squitieri F.; Horstink M.W.; Montagna P.; Libera A.D.; Stocchi F.; Goldwurm S.; Ferreira J.J.; Meco G.; Martignoni E.; Lopiano L.; Jardim L.B.; Oostra B.A.; Barbosa E.R.; Bonifati V.;
Neurology 68:1557-1562(2007)
Cited for: VARIANT KRS ARG-504; VARIANTS MET-12 AND ARG-533;

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)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS KRS MET-12; LEU-182; ARG-504; ARG-533; THR-746 AND ARG-877; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9NQ11: Variant p.Thr12Met