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UniProtKB/Swiss-Prot Q15046: Variant p.Glu525Lys

Lysine--tRNA ligase
Gene: KARS1
Variant information

Variant position:  525
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  US
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 Glutamate (E) to Lysine (K) at position 525 (E525K, p.Glu525Lys).
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 acidic (E) to large size and basic (K)
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:  Found in patients with severe infantile visual loss with progressive microcephaly and developmental delay as well as seizures and abnormal subcortical white matter; unknown pathological significance.
Any additional useful information about the variant.

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

Sequence information

Variant position:  525
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  597
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.

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 2 – 597 Lysine--tRNA ligase
Mutagenesis 540 – 540 G -> Y. Disrupts interaction with AIMP2 and the multisynthase complex. Increases production of diadenosine tetraphosphate (Ap4A). Almost complete loss of tRNA ligase activity.
Beta strand 524 – 526

Literature citations

Congenital Visual Impairment and Progressive Microcephaly Due to Lysyl-Transfer Ribonucleic Acid (RNA) Synthetase (KARS) Mutations: The Expanding Phenotype of Aminoacyl-Transfer RNA Synthetase Mutations in Human Disease.
McMillan H.J.; Humphreys P.; Smith A.; Schwartzentruber J.; Chakraborty P.; Bulman D.E.; Beaulieu C.L.; Majewski J.; Boycott K.M.; Geraghty M.T.;
J. Child Neurol. 30:1037-1043(2015)
Cited for: VARIANTS TRP-438 AND LYS-525;

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.