UniProtKB/Swiss-Prot Q68CP4: Variant p.Gly452Ser

Heparan-alpha-glucosaminide N-acetyltransferase
Chromosomal location: 8p11.1
Variant information

Variant position:  452
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 Glycine (G) to Serine (S) at position 452 (G452S, p.Gly452Ser).
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 glycine (G) to small size and polar (S)
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

Involvement in disease:  Mucopolysaccharidosis 3C (MPS3C) [MIM:252930]: A form of mucopolysaccharidosis type 3, an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate. MPS3 is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life. {ECO:0000269|PubMed:16960811, ECO:0000269|PubMed:17033958, ECO:0000269|PubMed:17397050, ECO:0000269|PubMed:18024218, ECO:0000269|PubMed:19479962, ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299, ECO:0000269|PubMed:20825431, ECO:0000269|PubMed:28101780}. 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 MPS3C; results in a negligible amount of protein synthesis; very low enzyme activity; retained in the endoplasmic reticulum.
Any additional useful information about the variant.

Sequence information

Variant position:  452
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  663
The length of the canonical sequence.

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.



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.

Chain 1 – 663 Heparan-alpha-glucosaminide N-acetyltransferase
Topological domain 442 – 500 Lumenal, vesicle
Disulfide bond 151 – 462
Mutagenesis 462 – 462 C -> S. Complete loss of intralysosomal proteolytic cleavage and enzymatic activity. Reduced oligomer formation.

Literature citations

Protein misfolding as an underlying molecular defect in mucopolysaccharidosis III type C.
Feldhammer M.; Durand S.; Pshezhetsky A.V.;
PLoS ONE 4:E7434-E7434(2009)
Cited for: FUNCTION; GLYCOSYLATION; CHARACTERIZATION OF VARIANT MPS3C THR-643; CHARACTERIZATION OF VARIANTS PHE-104; PRO-165; GLN-265; ARG-290; LYS-301; LEU-311; HIS-372; CYS-431; SER-452; LYS-499; LEU-509; LYS-510; GLU-517; PHE-546; GLN-551; CYS-567; LEU-569; VAL-590 AND LEU-599;

Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).
Hrebicek M.; Mrazova L.; Seyrantepe V.; Durand S.; Roslin N.M.; Noskova L.; Hartmannova H.; Ivanek R.; Cizkova A.; Poupetova H.; Sikora J.; Urinovska J.; Stranecky V.; Zeman J.; Lepage P.; Roquis D.; Verner A.; Ausseil J.; Beesley C.E.; Maire I.; Poorthuis B.J.H.M.; van de Kamp J.; van Diggelen O.P.; Wevers R.A.; Hudson T.J.; Fujiwara T.M.; Majewski J.; Morgan K.; Kmoch S.; Pshezhetsky A.V.;
Am. J. Hum. Genet. 79:807-819(2006)

Functional analysis of the HGSNAT gene in patients with mucopolysaccharidosis IIIC (Sanfilippo C Syndrome).
Fedele A.O.; Hopwood J.J.;
Hum. Mutat. 31:E1574-E1586(2010)
Cited for: CHARACTERIZATION OF VARIANTS MPS3C PHE-104; PRO-165; ARG-290; LEU-311; CYS-372; CYS-431; SER-452; LYS-499; LYS-510; GLU-514; GLU-517; PHE-546; CYS-567; LEU-569; VAL-590; LEU-599 AND THR-643; CHARACTERIZATION OF VARIANTS GLN-265; LEU-509 AND GLN-551;

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.