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UniProtKB/Swiss-Prot P04062: Variant p.Arg502Cys

Lysosomal acid glucosylceramidase
Gene: GBA
Variant information

Variant position:  502
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 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 GD; also found in patients with Parkinson disease; no effect on protein abundance; decreased glucosylceramidase activity; 37% of normal activity.
Any additional useful information about the variant.

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



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.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         DLDAVALMHPDGSAVVVVLNRSSKDVPLTIKDPAVGFLETI

Chimpanzee                    DLDAVALMHPDGSAVVVVLNRSSKDVPLTIKDPAVGFLETI

Mouse                         DLETVALLRPDGSAVVVVLNRSSEDVPLTISDPDLGFLETV

Pig                           NLDTVALLRPDGSAVVVVLNRSSKDVPLTIKDPALGFLETI

Bovine                        DLDTVALLRPDGSAVAVVLNRSSKDVPLTIKDPAVGFMETV

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 40 – 536 Lysosomal acid glucosylceramidase
Glycosylation 501 – 501 N-linked (GlcNAc...) asparagine
Alternative sequence 425 – 536 Missing. In isoform 3.


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 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;

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 GD TRP-87; ASN-118; THR-129; ASP-156; GLN-159; TRP-159; LEU-170; ILE-173; CYS-209; PRO-209; SER-227; THR-229; PRO-235; ARG-241; ILE-252; GLN-296; CYS-324; THR-380; MET-408; SER-409; SER-416; LEU-433; TYR-438; HIS-448; PRO-483 AND CYS-502; VARIANT LYS-365; VARIANT GD2 GLN-159;

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;

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.