UniProtKB/Swiss-Prot Q68CP4: Variant p.Ala643Thr

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

643 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Threonine (T) at position 643 (A643T, p.Ala643Thr). 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 polar (T) 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 RP73 and MPS3C; uncertain significance; may act as a modifier of disease severity in patients with retinitis pigmentosa; has a negligible effect on the enzyme expression; moderately reduced enzyme activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs112029032 [ dbSNP | Ensembl ]

Sequence information Variant position:

643 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:

FQWKLKDNQSHKEHLTQNIV A TALWVLIAYILYRKKIFWKI 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                         FQWKLKDNQSHKEHLTQNIVATALWVLIAYILYRKKIFWKI

Mouse                         FQWKLADEQSHKEHLIQNIVATALWVLIAYVLYKKKLFWKI

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.

Type	Positions	Description
Chain	1 – 663	Heparan-alpha-glucosaminide N-acetyltransferase
Transmembrane	635 – 655	Helical
Mutagenesis	633 – 633	H -> A. Loss of intralysosomal proteolytic cleavage and enzymatic activity, retained in the endoplasmic reticulum.

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 VARIANTS MPS3C LEU-509 AND 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; LYS-510; GLU-517; PHE-546; GLN-551; CYS-567; LEU-569; VAL-590 AND LEU-599; Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT).
Haer-Wigman L.; Newman H.; Leibu R.; Bax N.M.; Baris H.N.; Rizel L.; Banin E.; Massarweh A.; Roosing S.; Lefeber D.J.; Zonneveld-Vrieling M.N.; Isakov O.; Shomron N.; Sharon D.; Den Hollander A.I.; Hoyng C.B.; Cremers F.P.; Ben-Yosef T.;
Hum. Mol. Genet. 24:3742-3751(2015)
Cited for: INVOLVEMENT IN RP73; VARIANTS RP73 TRP-152; ALA-161 AND THR-643; CHARACTERIZATION OF VARIANT RP73 THR-643; 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)
Cited for: VARIANTS MPS3C PHE-104; GLN-265; LEU-311; CYS-372; HIS-372; CYS-431; SER-452; LYS-499; LYS-510; GLN-551; LEU-569; VAL-590; LEU-599 AND THR-643; FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; 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; GLN-265; LEU-311; CYS-372; CYS-431; LYS-499; LEU-509; GLU-514; GLU-517; PHE-546; GLN-551; LEU-569 AND THR-643; CHARACTERIZATION OF VARIANTS MPS3C GLN-265; CYS-431; LEU-509; GLN-551 AND THR-643; 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; GLN-265; ARG-290; LEU-311; CYS-372; CYS-431; SER-452; LYS-499; LEU-509; LYS-510; GLU-514; GLU-517; PHE-546; GLN-551; CYS-567; LEU-569; VAL-590; LEU-599 AND THR-643;

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.