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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43776: Variant p.Thr17Met

Asparagine--tRNA ligase, cytoplasmic
Gene: NARS1
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Variant information Variant position: help 17 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 Threonine (T) to Methionine (M) at position 17 (T17M, p.Thr17Met). 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 medium size and polar (T) to medium size and hydrophobic (M) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In NEDMILG; decreased protein levels in patient cells; decreased asparagine-tRNA ligase activity in patient cells. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 17 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 MVLAELYVSDREGSDA T GDGTKEKPFKTGLKALMTVG 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                         MVLAEL--YVSDRE---GSDA-TGD---------------------GTKEKPFKTGLK-------------------------ALMTVG

Mouse                         MVLAEL--YVSDRE---GNDA-TGD------------

Bovine                        MVLAEL--YVSDRE---GNDV-TGD------------

Caenorhabditis elegans        --MSKL--YIDTDA---GSDQ-H-P------------

Slime mold                    TALLKT--IIEEASVSKGCDKSIGNLLYSLATCQQVN

Baker's yeast                 --MSSL--YIKEAT---GVDELTTA------------

Fission yeast                 KIKSDVVFYIDEAS---GNDE-TGN------------
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
Region 1 – 25 Disordered
Turn 15 – 17



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; Loss of NARS1 impairs progenitor proliferation in cortical brain organoids and leads to microcephaly.
Wang L.; Li Z.; Sievert D.; Smith D.E.C.; Mendes M.I.; Chen D.Y.; Stanley V.; Ghosh S.; Wang Y.; Kara M.; Aslanger A.D.; Rosti R.O.; Houlden H.; Salomons G.S.; Gleeson J.G.;
Nat. Commun. 11:4038-4038(2020)
Cited for: INVOLVEMENT IN NEDMILG; VARIANTS NEDMILG MET-17; ALA-356 AND CYS-545; CHARACTERIZATION OF VARIANT NEDMILG MET-17; 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.