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UniProtKB/Swiss-Prot P51688: Variant p.Arg74Cys

N-sulphoglucosamine sulphohydrolase
Gene: SGSH
Variant information

Variant position:  74
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 Arginine (R) to Cysteine (C) at position 74 (R74C, p.Arg74Cys).
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 large size and basic (R) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 MPS3A; intermediate/severe; the mutant is enzymatically inactive; rapid degradation rather than decrease in synthesis is responsible for the low steady state level of the mutant protein in cells; the majority of newly synthesized protein probably occurs in the endoplasmic reticulum.
Any additional useful information about the variant.

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



Sequence information

Variant position:  74
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  502
The length of the canonical sequence.

Location on the sequence:   ARRSLLFRNAFTSVSSCSPS  R ASLLTGLPQHQNGMYGLHQD
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.

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 21 – 502 N-sulphoglucosamine sulphohydrolase
Active site 70 – 70 Nucleophile
Metal binding 70 – 70 Calcium; via 3-oxoalanine
Modified residue 70 – 70 3-oxoalanine (Cys)
Helix 70 – 77


Literature citations

Identification of molecular defects in Italian Sanfilippo A patients including 13 novel mutations.
di Natale P.; Balzano N.; Esposito S.; Villani G.R.D.;
Hum. Mutat. 11:313-320(1998)
Cited for: VARIANTS MPS3A ASN-40; THR-44; TRP-66; CYS-74; ARG-122; LEU-128; PRO-146; GLN-150; ASN-179; CYS-182; ARG-227; LYS-369 AND CYS-377; VARIANTS ALA-226 AND HIS-456;

Mutational analysis of Sanfilippo syndrome type A (MPS IIIA): identification of 13 novel mutations.
Beesley C.E.; Young E.P.; Vellodi A.; Winchester B.G.;
J. Med. Genet. 37:704-707(2000)
Cited for: VARIANTS MPS3A GLY-32; TRP-66; CYS-74; PRO-79; TYR-84; ARG-122; TRP-150; ASN-235; HIS-245; ASN-273; PRO-298; SER-322; LYS-355; HIS-374; GLN-ARG-381 INS; TRP-433; 436-TRP--LEU-438 DEL AND PHE-486; VARIANT HIS-456;

Sanfilippo syndrome in Turkey: identification of novel mutations in subtypes A and B.
Emre S.; Terzioglu M.; Tokatli A.; Coskun T.; Ozalp I.; Weber B.; Hopwood J.J.;
Hum. Mutat. 19:184-185(2002)
Cited for: VARIANTS MPS3A CYS-74 AND SER-288;

Transport, enzymatic activity, and stability of mutant sulfamidase (SGSH) identified in patients with mucopolysaccharidosis type III A.
Muschol N.; Storch S.; Ballhausen D.; Beesley C.; Westermann J.-C.; Gal A.; Ullrich K.; Hopwood J.J.; Winchester B.; Braulke T.;
Hum. Mutat. 23:559-566(2004)
Cited for: VARIANTS MPS3A CYS-74; ARG-106; PRO-163; ARG-191; TYR-403 DEL AND TRP-433; CHARACTERIZATION OF VARIANTS MPS3A CYS-74; ARG-106; PRO-163; ARG-191; TYR-403 DEL AND TRP-433; CATALYTIC ACTIVITY; FUNCTION; SUBCELLULAR LOCATION;

The mutation p.Ser298Pro in the sulphamidase gene (SGSH) is associated with a slowly progressive clinical phenotype in mucopolysaccharidosis type IIIA (Sanfilippo A syndrome).
Meyer A.; Kossow K.; Gal A.; Steglich C.; Muehlhausen C.; Ullrich K.; Braulke T.; Muschol N.;
Hum. Mutat. 29:770-770(2008)
Cited for: VARIANTS MPS3A GLU-32; CYS-74; HIS-245; ALA-251 AND PRO-298; ASSOCIATION OF VARIANT MPS3A PRO-298 WITH SLOWLY PROGRESSIVE PHENOTYPE;

Residual activity and proteasomal degradation of p.Ser298Pro sulfamidase identified in patients with a mild clinical phenotype of Sanfilippo A syndrome.
Muschol N.; Pohl S.; Meyer A.; Gal A.; Ullrich K.; Braulke T.;
Am. J. Med. Genet. A 155A:1634-1639(2011)
Cited for: VARIANTS MPS3A TRP-66; CYS-74; HIS-245; ALA-251 AND PRO-298; CHARACTERIZATION OF VARIANT MPS3A PRO-298;

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.