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UniProtKB/Swiss-Prot Q99519: Variant p.Ala298Val

Sialidase-1
Gene: NEU1
Variant information

Variant position:  298
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 298 (A298V, p.Ala298Val).
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 SIALIDOSIS; type 2; less than 10% of activity; rapid intralysosomal degradation; impaired enzyme folding.
Any additional useful information about the variant.

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



Sequence information

Variant position:  298
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  415
The length of the canonical sequence.

Location on the sequence:   NARNQNNYHCHCRIVLRSYD  A CDTLRPRDVTFDPELVDPVV
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                         NARNQNNYHCHCRIVLRSYDACDTLRPRDVTFDPELVDPVV

Mouse                         NARNQNNYHCRCRIVLRSYDACDTLRPRDVTFDPELVDPVV

Rat                           NARNQNNYHCRCRIVLRSYDACDTLRPRDVTFDPELVDPVV

Pig                           NARNQNNYHCRCRIVLRSYDACDTLRPRDVTFDPELVDPVV

Bovine                        NARNQNNYHCHCRIILRSYDACDTLRPRDVTFDTELVDPVV

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 48 – 415 Sialidase-1
Binding site 280 – 280 Substrate


Literature citations

Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex.
Lukong K.E.; Elsliger M.-A.; Chang Y.; Richard C.; Thomas G.; Carey W.; Tylki-Szymanska A.; Czartoryska B.; Buchholz T.; Rodriguez Criado G.; Palmeri S.; Pshezhetsky A.V.;
Hum. Mol. Genet. 9:1075-1085(2000)
Cited for: CHARACTERIZATION OF VARIANTS SIALIDOSIS VAL-68; GLY-182; ARG-227; TYR-260; PHE-270; VAL-298; SER-328 AND PRO-363;

Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis.
Bonten E.J.; Arts W.F.; Beck M.; Covanis A.; Donati M.A.; Parini R.; Zammarchi E.; d'Azzo A.;
Hum. Mol. Genet. 9:2715-2725(2000)
Cited for: VARIANTS SIALIDOSIS MET-54; VAL-68; ARG-91; GLY-182; ALA-219; ARG-227; HIS-231; TYR-260; PRO-270; SER-294; VAL-298; SER-328; GLN-335; PRO-363; CYS-370 AND HIS-TYR-400 INS;

Mutations in sialidosis impair sialidase binding to the lysosomal multienzyme complex.
Lukong K.E.; Landry K.; Elsliger M.-A.; Chang Y.; Lefrancois S.; Morales C.R.; Pshezhetsky A.V.;
J. Biol. Chem. 276:17286-17290(2001)
Cited for: VARIANTS SIALIDOSIS VAL-68; GLY-182; ARG-227; ARG-240; TYR-260; PHE-270; VAL-298; SER-328 AND PRO-363; CHARACTERIZATION OF VARIANTS SIALIDOSIS VAL-68; GLY-182; ARG-227; TYR-260; PHE-270; VAL-298; SER-328 AND PRO-363;

Five novel mutations in the lysosomal sialidase gene (NEU1) in type II sialidosis patients and assessment of their impact on enzyme activity and intracellular targeting using adenovirus-mediated expression.
Pattison S.; Pankarican M.; Rupar C.A.; Graham F.L.; Igdoura S.A.;
Hum. Mutat. 23:32-39(2004)
Cited for: VARIANTS SIALIDOSIS PRO-225; VAL-298 AND GLY-341; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS SIALIDOSIS PRO-225; VAL-298 AND GLY-341;

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.