UniProtKB/Swiss-Prot P54886: Variant p.Val243Leu

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 243 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Valine (V) to Leucine (L) at position 243 (V243L, p.Val243Leu). 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: 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 SPG9A; decreased protein abundance; no effect on localization to the mitochondrion; altered homohexamerization; loss of glutamate 5-kinase activity; no effect on glutamate-5-semialdehyde dehydrogenase activity; decreased amino acid biosynthetic process. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs864321669 [ dbSNP | Ensembl ]

Sequence information

Variant position: 243 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 795 The length of the canonical sequence.
Location on the sequence: DAVVPPAEPNSDLQGVNVIS V KDNDSLAARLAVEMKTDLLI 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.

Type	Positions	Description
Chain	1 – 795	Delta-1-pyrroline-5-carboxylate synthase
Region	1 – 361	Glutamate 5-kinase
Binding site	223 – 223
Binding site	246 – 246

Literature citations

ALDH18A1 gene mutations cause dominant spastic paraplegia SPG9: loss of function effect and plausibility of a dominant negative mechanism.
Panza E.; Escamilla-Honrubia J.M.; Marco-Marin C.; Gougeard N.; De Michele G.; Morra V.B.; Liguori R.; Salviati L.; Donati M.A.; Cusano R.; Pippucci T.; Ravazzolo R.; Nemeth A.H.; Smithson S.; Davies S.; Hurst J.A.; Bordo D.; Rubio V.; Seri M.;
Brain 139:E3-E3(2016)
Cited for: FUNCTION; CATALYTIC ACTIVITY; PATHWAY; SUBUNIT; SUBCELLULAR LOCATION; INVOLVEMENT IN SPG9A; VARIANTS SPG9A LEU-243 AND GLN-252; CHARACTERIZATION OF VARIANTS SPG9A LEU-243 AND GLN-252;