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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y223: Variant p.Asn519Ser

Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
Gene: GNE
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Variant information Variant position: help 519 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 Asparagine (N) to Serine (S) at position 519 (N519S, p.Asn519Ser). 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 (N) to small size and polar (S) 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 NM and THC12; likely pathogenic; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 519 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 722 The length of the canonical sequence.
Location on the sequence: help DLRTPLSDTLHLPVWVDNDG N CAALAERKFGQGKGLENFVT 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                         DLRTPLSDTLHLPVWVDNDGNCAALAERKFGQGKGLENFVT

Mouse                         DLRTPLSDTLHLPVWVDNDGNCAAMAERKFGQGKGQENFVT

Rat                           DLRTPLSDTLHLPVWVDNDGNCAAMAERKFGQGKGQENFVT
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 – 722 Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
Region 406 – 722 N-acetylmannosamine kinase
Active site 517 – 517
Binding site 516 – 516
Binding site 516 – 516
Binding site 517 – 517
Binding site 517 – 517
Alternative sequence 471 – 544 Missing. In isoform 4.
Mutagenesis 517 – 517 D -> AN. Loss of N-acylmannosamine kinase activity. Decreased affinity for N-acyl-D-mannosamine. No effect on structure.
Helix 517 – 527



Literature citations
Crystal structures of N-acetylmannosamine kinase provide insights into enzyme activity and inhibition.
Martinez J.; Nguyen L.D.; Hinderlich S.; Zimmer R.; Tauberger E.; Reutter W.; Saenger W.; Fan H.; Moniot S.;
J. Biol. Chem. 287:13656-13665(2012)
Cited for: X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) OF 406-720 IN COMPLEX WITH N-ACYL-D-MANNOSAMINE; N-ACYL-D-MANNOSAMINE 6-PHOSPHATE; ADP; MAGNESIUM AND ZINC; ZINC-BINDING SITES; ACTIVE SITE; SUBUNIT; MUTAGENESIS OF ASP-517; CHARACTERIZATION OF VARIANTS SER-519; CYS-528; THR-587; VAL-631; THR-631 AND THR-712; Novel GNE mutations in Italian families with autosomal recessive hereditary inclusion-body myopathy.
Broccolini A.; Ricci E.; Cassandrini D.; Gliubizzi C.; Bruno C.; Tonoli E.; Silvestri G.; Pescatori M.; Rodolico C.; Sinicropi S.; Servidei S.; Zara F.; Minetti C.; Tonali P.A.; Mirabella M.;
Hum. Mutat. 23:632-632(2004)
Cited for: VARIANTS NM SER-27; SER-206; GLN-246; SER-519 AND THR-600; Influence of UDP-GlcNAc 2-epimerase/ManNAc kinase mutant proteins on hereditary inclusion body myopathy.
Penner J.; Mantey L.R.; Elgavish S.; Ghaderi D.; Cirak S.; Berger M.; Krause S.; Lucka L.; Voit T.; Mitrani-Rosenbaum S.; Hinderlich S.;
Biochemistry 45:2968-2977(2006)
Cited for: CHARACTERIZATION OF VARIANTS NM TYR-378; SER-519; CYS-528; GLU-576 AND THR-587; FUNCTION; CATALYTIC ACTIVITY; PATHWAY; GNE variants causing autosomal recessive macrothrombocytopenia without associated muscle wasting.
Revel-Vilk S.; Shai E.; Turro E.; Jahshan N.; Hi-Am E.; Spectre G.; Daum H.; Kalish Y.; Althaus K.; Greinacher A.; Kaplinsky C.; Izraeli S.; Mapeta R.; Deevi S.V.V.; Jarocha D.; Ouwehand W.H.; Downes K.; Poncz M.; Varon D.; Lambert M.P.;
Blood 132:1851-1854(2018)
Cited for: VARIANTS THC12 TYR-157; PHE-475; PRO-486 AND SER-519; INVOLVEMENT IN THC12;
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.