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UniProtKB/Swiss-Prot Q68CP4: Variant p.Ser546Phe

Heparan-alpha-glucosaminide N-acetyltransferase
Gene: HGSNAT
Variant information

Variant position:  546
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 Serine (S) to Phenylalanine (F) at position 546 (S546F, p.Ser546Phe).
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 polar (S) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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:  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:  546
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

Location on the sequence:   ARTKDILIRFTAWCCILGLI  S VALTKVSENEGFIPVNKNLW
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                         ARTKDILIRFTAWCCILGLISVALTKVSENEGFIPVNKNLW

Mouse                         DQTKAILTRFAAWCCILGLISIVLTKVSANEGFIPINKNLW

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 1 – 663 Heparan-alpha-glucosaminide N-acetyltransferase
Transmembrane 530 – 550 Helical


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;

Mutational analysis of the HGSNAT gene in Italian patients with mucopolysaccharidosis IIIC (Sanfilippo C syndrome). Mutation in brief #959. Online.
Fedele A.O.; Filocamo M.; Di Rocco M.; Sersale G.; Luebke T.; di Natale P.; Cosma M.P.; Ballabio A.;
Hum. Mutat. 28:523-523(2007)
Cited for: VARIANTS MPS3C PRO-165 AND PHE-546; VARIANT GLN-265;

Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The Netherlands.
Ruijter G.J.G.; Valstar M.J.; van de Kamp J.M.; van der Helm R.M.; Durand S.; van Diggelen O.P.; Wevers R.A.; Poorthuis B.J.; Pshezhetsky A.V.; Wijburg F.A.;
Mol. Genet. Metab. 93:104-111(2008)
Cited for: VARIANTS MPS3C PRO-165; ARG-280; LYS-301; CYS-372; LYS-499; PHE-546 AND CYS-567; VARIANT GLN-265;

Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene.
Feldhammer M.; Durand S.; Mrazova L.; Boucher R.-M.; Laframboise R.; Steinfeld R.; Wraith J.E.; Michelakakis H.; van Diggelen O.P.; Hrebicek M.; Kmoch S.; Pshezhetsky A.V.;
Hum. Mutat. 30:918-925(2009)
Cited for: VARIANTS MPS3C PRO-165; LEU-311; CYS-372; CYS-431; LYS-499; GLU-514; GLU-517; PHE-546; LEU-569 AND THR-643; VARIANTS GLN-265; LEU-509 AND GLN-551; CHARACTERIZATION OF VARIANTS MPS3C CYS-431 AND THR-643; CHARACTERIZATION OF VARIANTS GLN-265; LEU-509 AND GLN-551;

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;

Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.
Canals I.; Elalaoui S.C.; Pineda M.; Delgadillo V.; Szlago M.; Jaouad I.C.; Sefiani A.; Chabas A.; Coll M.J.; Grinberg D.; Vilageliu L.;
Clin. Genet. 80:367-374(2011)
Cited for: VARIANTS MPS3C VAL-82; PRO-141; VAL-452 AND PRO-473; VARIANT GLN-265; CHARACTERIZATION OF VARIANTS MPS3C VAL-82; PRO-141; CYS-372; VAL-452; PRO-473 AND PHE-546; CHARACTERIZATION OF VARIANT GLN-265;

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.