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UniProtKB/Swiss-Prot P41250: Variant p.Ala111Val

Glycine--tRNA ligase
Gene: GARS1
Variant information

Variant position:  111
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 Alanine (A) to Valine (V) at position 111 (A111V, p.Ala111Val).
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 hydrophobic (A) to medium size and hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 CMT2D; shows a reduction in aminoacylation activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  111
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:   VDKAVAELKARKRVLEAKEL  A LQPKDDIVDRAKMEDTLKRR
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                         VDKAVAELKARKRVLEAKELALQPKDDIVDRAKMEDTLKRR

Mouse                         VDRAVAELKARKRVLEAKELALQPKDDIVDRAKMEDTLKRR

Rat                           VDRAVAELKARKRVLEAKELALQPKDDIVDRAKMEDTLKRR

Caenorhabditis elegans        IDKAVVELKARKRLLEDTEIALAPKEASFDRLKLEDLLKRR

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 37 – 739 Glycine--tRNA ligase
Domain 63 – 119 WHEP-TRS
Mutagenesis 121 – 121 R -> A. Decrease in catalytic activity by about 10-fold.
Helix 95 – 112


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 (ISOFORM 2); 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;

Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome.
Rohkamm B.; Reilly M.M.; Lochmueller H.; Schlotter-Weigel B.; Barisic N.; Schoels L.; Nicholson G.; Pareyson D.; Laura M.; Janecke A.R.; Miltenberger-Miltenyi G.; John E.; Fischer C.; Grill F.; Wakeling W.; Davis M.; Pieber T.R.; Auer-Grumbach M.;
J. Neurol. Sci. 263:100-106(2007)
Cited for: VARIANT CMT2D VAL-111;

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.