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UniProtKB/Swiss-Prot P47897: Variant p.Arg515Trp

Glutamine--tRNA ligase
Gene: QARS
Variant information

Variant position:  515
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
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 Arginine (R) to Tryptophan (W) at position 515 (R515W, p.Arg515Trp).
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 large size and basic (R) to large size and aromatic (W)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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

Involvement in disease:  Microcephaly, progressive, with seizures and cerebral and cerebellar atrophy (MSCCA) [MIM:615760]: A severe, autosomal recessive, neurodevelopmental and neurodegenerative disorder characterized by progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, resulting in profoundly delayed development and hypotonia. {ECO:0000269|PubMed:24656866, ECO:0000269|PubMed:26869582}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In MSCCA; results in loss of glutaminyl-tRNA aminoacylation activity; impairs protein folding; results in reduced protein solubility.
Any additional useful information about the variant.

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



Sequence information

Variant position:  515
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  775
The length of the canonical sequence.

Location on the sequence:   SKRKILQLVATGAVRDWDDP  R LFTLTALRRRGFPPEAINNF
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.

TypePositionsDescription
Chain 2 – 775 Glutamine--tRNA ligase
Modified residue 495 – 495 Phosphoserine


Literature citations

Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures.
Zhang X.; Ling J.; Barcia G.; Jing L.; Wu J.; Barry B.J.; Mochida G.H.; Hill R.S.; Weimer J.M.; Stein Q.; Poduri A.; Partlow J.N.; Ville D.; Dulac O.; Yu T.W.; Lam A.T.; Servattalab S.; Rodriguez J.; Boddaert N.; Munnich A.; Colleaux L.; Zon L.I.; Soll D.; Walsh C.A.; Nabbout R.;
Am. J. Hum. Genet. 94:547-558(2014)
Cited for: FUNCTION; TISSUE SPECIFICITY; SUBCELLULAR LOCATION; INTERACTION WITH RARS; VARIANTS MSCCA VAL-45; HIS-57; TRP-403 AND TRP-515; CHARACTERIZATION OF VARIANTS MSCCA VAL-45; HIS-57; TRP-403 AND TRP-515;

The crystal structure of human GlnRS provides basis for the development of neurological disorders.
Ognjenovic J.; Wu J.; Matthies D.; Baxa U.; Subramaniam S.; Ling J.; Simonovic M.;
Nucleic Acids Res. 44:3420-3431(2016)
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF WILD-TYPE AND VARIANTS MSCCA VAL-45 AND HIS-57; FUNCTION; CATALYTIC ACTIVITY; SUBUNIT; MUTAGENESIS OF HIS-175; CHARACTERIZATION OF VARIANTS MSCCA VAL-45; HIS-57; TRP-403 AND TRP-515;

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.