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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43776: Variant p.Arg322Leu

Asparagine--tRNA ligase, cytoplasmic
Gene: NARS1
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Variant information Variant position: help 322 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Arginine (R) to Leucine (L) at position 322 (R322L, p.Arg322Leu). 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: help Change from large size and basic (R) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In NEDMILEG; unable to rescue growth defects in a yeast complementation assay. Any additional useful information about the variant.


Sequence information Variant position: help 322 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 548 The length of the canonical sequence.
Location on the sequence: help LYLETCLPALGDVFCIAQSY R AEQSRTRRHLAEYTHVEAEC 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         LYLETCLPALGDVFCIAQSYRAEQSRTRRHLAEYTHVEAEC

Mouse                         LYLETCLPALGDVFCIAQSYRAEQSRTRRHLAEFTHVEAEC

Bovine                        LYLETCIPALGDVFCIAQSYRAEQSRTRRHLAEYTHVEAEC

Caenorhabditis elegans        LYLETCNAALGDVYCISQSYRAEKSRTRRHLSEYQHVEAEC

Slime mold                    LYLETMLPVLGDNFTITQSYRAEKARTRRHLTEFLHLEAEC

Baker's yeast                 LYLETCLASLGDVYTIQESFRAEKSHTRRHLSEYTHIEAEL

Fission yeast                 LYLEAALPALGSVYTIQESFRAEKSLTRRHLSEFTHVEFEL
Sequence annotation in neighborhood: help 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 – 548 Asparagine--tRNA ligase, cytoplasmic
Alternative sequence 174 – 547 Missing. In isoform 2.



Literature citations
De novo and bi-allelic pathogenic variants in NARS1 cause neurodevelopmental delay due to toxic gain-of-function and partial loss-of-function effects.
Manole A.; Efthymiou S.; O'Connor E.; Mendes M.I.; Jennings M.; Maroofian R.; Davagnanam I.; Mankad K.; Lopez M.R.; Salpietro V.; Harripaul R.; Badalato L.; Walia J.; Francklyn C.S.; Athanasiou-Fragkouli A.; Sullivan R.; Desai S.; Baranano K.; Zafar F.; Rana N.; Ilyas M.; Horga A.; Kara M.; Mattioli F.; Goldenberg A.; Griffin H.; Piton A.; Henderson L.B.; Kara B.; Aslanger A.D.; Raaphorst J.; Pfundt R.; Portier R.; Shinawi M.; Kirby A.; Christensen K.M.; Wang L.; Rosti R.O.; Paracha S.A.; Sarwar M.T.; Jenkins D.; Ahmed J.; Santoni F.A.; Ranza E.; Iwaszkiewicz J.; Cytrynbaum C.; Weksberg R.; Wentzensen I.M.; Guillen Sacoto M.J.; Si Y.; Telegrafi A.; Andrews M.V.; Baldridge D.; Gabriel H.; Mohr J.; Oehl-Jaschkowitz B.; Debard S.; Senger B.; Fischer F.; van Ravenwaaij C.; Fock A.J.M.; Stevens S.J.C.; Baehler J.; Nasar A.; Mantovani J.F.; Manzur A.; Sarkozy A.; Smith D.E.C.; Salomons G.S.; Ahmed Z.M.; Riazuddin S.; Riazuddin S.; Usmani M.A.; Seibt A.; Ansar M.; Antonarakis S.E.; Vincent J.B.; Ayub M.; Grimmel M.; Jelsig A.M.; Hjortshoej T.D.; Karstensen H.G.; Hummel M.; Haack T.B.; Jamshidi Y.; Distelmaier F.; Horvath R.; Gleeson J.G.; Becker H.; Mandel J.L.; Koolen D.A.; Houlden H.;
Am. J. Hum. Genet. 107:311-324(2020)
Cited for: VARIANTS NEDMILG PRO-11; MET-17; GLU-60; 90-ARG--PRO-548 DEL; CYS-132; PRO-350; ALA-356; THR-422; ILE-459 AND CYS-545; VARIANTS NEDMILEG LEU-322; SER-509 AND 534-ARG--PRO-548 DEL; INVOLVEMENT IN NEDMILG; INVOLVEMENT IN NEDMILEG; CHARACTERIZATION OF VARIANT NEDMILG PRO-11; CHARACTERIZATION OF VARIANTS NEDMILEG LEU-322 AND 534-ARG--PRO-548 DEL; FUNCTION; CATALYTIC ACTIVITY;
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.