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UniProtKB/Swiss-Prot P41250: Variant p.Ser635Leu

Glycine--tRNA ligase
Gene: GARS
Chromosomal location: 7p15
Variant information

Variant position:  635
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Serine (S) to Leucine (L) at position 635 (S635L, p.Ser635Leu).
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 small size and polar (S) to medium size and hydrophobic (L)
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

Variant description:  Polymorphism; has no effect on subcellular localization; results in reduced activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  635
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  739
The length of the canonical sequence.

Location on the sequence:   KCSVLPLSQNQEFMPFVKEL  S EALTRHGVSHKVDDSSGSIG
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                         KCSVLPLSQNQEFMPFVKELSEALTRHGVSHKVDDSSGSIG

Mouse                         KCSVLPLSQNQEFMPFVKELSEALTRNGVSHKVDDSSGSIG

Caenorhabditis elegans        KCSVLPISANDTLIPVMDAVKEELSRFEMSYKVDDSSGTIG

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 – 739 Glycine--tRNA ligase
Helix 628 – 640


Literature citations

Impaired function is a common feature of neuropathy-associated glycyl-tRNA synthetase mutations.
Griffin L.B.; Sakaguchi R.; McGuigan D.; Gonzalez M.A.; Searby C.; Zuchner S.; Hou Y.M.; Antonellis A.;
Hum. Mutat. 35:1363-1371(2014)
Cited for: SUBCELLULAR LOCATION; VARIANTS CMT2D VAL-111; ASN-200; PHE-265; ARG-294; LEU-298; PHE-334; ARG-472; ASN-554; ARG-580 AND ALA-652; VARIANT LEU-635; CHARACTERIZATION OF VARIANTS CMT2D VAL-111; GLY-125; PRO-183; ASN-200; PHE-265; ARG-294; LEU-298; PHE-334; ARG-472; ASN-554; ARG-580 AND ALA-652; CHARACTERIZATION OF VARIANT LEU-635;

Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy.
Cader M.Z.; Ren J.; James P.A.; Bird L.E.; Talbot K.; Stammers D.K.;
FEBS Lett. 581:2959-2964(2007)
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 55-739; FUNCTION; SUBUNIT; CHARACTERIZATION OF VARIANT LEU-635; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES;

Severe childhood SMA and axonal CMT due to anticodon binding domain mutations in the GARS gene.
James P.A.; Cader M.Z.; Muntoni F.; Childs A.M.; Crow Y.J.; Talbot K.;
Neurology 67:1710-1712(2006)
Cited for: VARIANT LEU-635; VARIANTS CMT2D PHE-334 AND ALA-652;

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.