UniProtKB/Swiss-Prot P04062: Variant p.Arg502Cys

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 502 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 502 (R502C, p.Arg502Cys). 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 GD1 and GD2; also found in patients with Parkinson disease; no effect on protein abundance; decreased glucosylceramidase activity. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs80356771 [ dbSNP | Ensembl ]

Sequence information

Variant position: 502 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 536 The length of the canonical sequence.
Location on the sequence: DLDAVALMHPDGSAVVVVLN R SSKDVPLTIKDPAVGFLETI 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.

Type	Positions	Description
Chain	40 – 536	Lysosomal acid glucosylceramidase
Glycosylation	501 – 501	N-linked (GlcNAc...) asparagine
Alternative sequence	425 – 536	Missing. In isoform 3.
Mutagenesis	482 – 482	D -> E. Loss of glucosylceramidase activity.
Mutagenesis	482 – 482	D -> G. Decreased glucosylceramidase activity.
Mutagenesis	482 – 482	D -> S. Severe decrease of glucosylceramidase activity.
Mutagenesis	501 – 501	N -> D. Loss of glucosylceramidase activity.
Mutagenesis	501 – 501	N -> Q. Loss of glucosylceramidase activity.

Literature citations

Analyses of variant acid beta-glucosidases: effects of Gaucher disease mutations.
Liou B.; Kazimierczuk A.; Zhang M.; Scott C.R.; Hegde R.S.; Grabowski G.A.;
J. Biol. Chem. 281:4242-4253(2006)
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 40-536; CATALYTIC ACTIVITY; PATHWAY; CHARACTERIZATION OF VARIANTS GD SER-55; GLN-87; ASN-118; LEU-161; VAL-162; VAL-166; ASN-200; PHE-213; PHE-224; GLU-232; GLU-237; LEU-298; ILE-303; CYS-343; ILE-362; LYS-365; GLY-381; LYS-388; TRP-392; CYS-402; SER-409; VAL-410; HIS-419; LYS-421; ARG-429; LEU-433; SER-436; ASN-438; HIS-448; VAL-455; PRO-483; PRO-500; CYS-502 AND PRO-502; CHARACTERIZATION OF VARIANT GD2 GLN-159; MUTAGENESIS OF CYS-43; CYS-57 AND CYS-62; Sequence of two alleles responsible for Gaucher disease.
Hong C.M.; Ohashi T.; Yu X.J.; Weiler S.; Barranger J.A.;
DNA Cell Biol. 9:233-241(1990)
Cited for: VARIANT GD CYS-502; CHARACTERIZATION OF VARIANT GD CYS-502; Gaucher disease: four rare alleles encoding F213I, P289L, T323I, and R463C in type 1 variants.
He G.S.; Grace M.E.; Grabowski G.A.;
Hum. Mutat. 1:423-427(1992)
Cited for: VARIANTS GD1 ILE-252; LEU-328; ILE-362 AND CYS-502; CHARACTERIZATION OF VARIANTS GD1 LEU-328; ILE-362 AND CYS-502; Analysis of human acid beta-glucosidase by site-directed mutagenesis and heterologous expression.
Grace M.E.; Newman K.M.; Scheinker V.; Berg-Fussman A.; Grabowski G.A.;
J. Biol. Chem. 269:2283-2291(1994)
Cited for: CHARACTERIZATION OF VARIANT GD TYR-255; CHARACTERIZATION OF VARIANTS GD1 LEU-328; ILE-362; THR-403; SER-409; LEU-433; HIS-448; PRO-483; PRO-495 AND CYS-502; CHARACTERIZATION OF VARIANT GD2 ARG-454; CHARACTERIZATION OF VARIANT GD3 VAL-448; MUTAGENESIS OF ASP-482 AND ASN-501; Gaucher disease in Spanish patients: analysis of eight mutations.
Cormand B.; Vilageliu L.; Burguera J.M.; Balcells S.; Gonzalez-Duarte R.; Grinberg D.; Chabas A.;
Hum. Mutat. 5:303-309(1995)
Cited for: VARIANTS GD SER-409; HIS-448; PRO-483 AND CYS-502; Characterization of glucocerebrosidase in Greek Gaucher disease patients: mutation analysis and biochemical studies.
Michelakakis H.; Dimitriou E.; Van Weely S.; Boot R.G.; Mavridou I.; Verhoek M.; Aerts J.M.;
J. Inherit. Metab. Dis. 18:609-615(1995)
Cited for: VARIANTS GD1 SER-409 AND PRO-483; VARIANTS GD2 HIS-448; PRO-483 AND CYS-502; VARIANTS GD3 HIS-448 AND PRO-483; Exhaustive screening of the acid beta-glucosidase gene, by fluorescence-assisted mismatch analysis using universal primers: mutation profile and genotype/phenotype correlations in Gaucher disease.
Germain D.P.; Puech J.-P.; Caillaud C.; Kahn A.; Poenaru L.;
Am. J. Hum. Genet. 63:415-427(1998)
Cited for: VARIANTS GD1 TRP-87; THR-158; TRP-159; PRO-209; LYS-227; PRO-276; ILE-342; PRO-363; SER-409; SER-416; PRO-483; PRO-485 AND CYS-502; VARIANTS GD3 LEU-433 AND PRO-483; Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease.
Koprivica V.; Stone D.L.; Park J.K.; Callahan M.; Frisch A.; Cohen I.J.; Tayebi N.; Sidransky E.;
Am. J. Hum. Genet. 66:1777-1786(2000)
Cited for: VARIANTS GD1 TRP-87; ASN-118; THR-129; ASP-156; GLN-159; TRP-159; LEU-170; ILE-173; CYS-209; PRO-209; SER-227; PRO-235; ARG-241; ILE-252; GLN-296; CYS-324; LYS-365; THR-380; MET-408; SER-409; SER-416; LEU-433; TYR-438; HIS-448; PRO-483 AND CYS-502; VARIANT GD2 GLN-159; VARIANTS GD3 THR-229; HIS-448; PRO-483 AND CYS-502; Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease.
Neumann J.; Bras J.; Deas E.; O'Sullivan S.S.; Parkkinen L.; Lachmann R.H.; Li A.; Holton J.; Guerreiro R.; Paudel R.; Segarane B.; Singleton A.; Lees A.; Hardy J.; Houlden H.; Revesz T.; Wood N.W.;
Brain 132:1783-1794(2009)
Cited for: INVOLVEMENT IN PARKINSON DISEASE; VARIANTS GLU-46; CYS-170; GLU-232; GLN-296; SER-409; ALA-419; HIS-448; ASN-482; PRO-483; PRO-495; LEU-497 AND CYS-502;