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UniProtKB/Swiss-Prot P04062: Variant p.Leu483Pro

Lysosomal acid glucosylceramidase
Gene: GBA
Variant information

Variant position:  483
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 Leucine (L) to Proline (P) at position 483 (L483P, p.Leu483Pro).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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; common mutation; associated with susceptibility to Parkinson disease; gene conversion; alters protein stability; increased proteasomal degradation; decreased protein abundance; very low glucosylceramide catabolic process; no effect on glucosylceramidase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  483
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:   SKFIPEGSQRVGLVASQKND  L DAVALMHPDGSAVVVVLNRS
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                         SKFIPEGSQRVGLVASQKNDLDAVALMHPDGSAVVVVLNRS

Chimpanzee                    SKFIPEGSQRVGLVASQKNDLDAVALMHPDGSAVVVVLNRS

Mouse                         SKFIPEGSQRVALVASESTDLETVALLRPDGSAVVVVLNRS

Pig                           SKFIPEGSQRVGLAASEKNNLDTVALLRPDGSAVVVVLNRS

Bovine                        SKFIPEGSQRVGLVASKKSDLDTVALLRPDGSAVAVVLNRS

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.
Beta strand 482 – 489


Literature citations

Decreased glucocerebrosidase activity in Gaucher disease parallels quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl.
Lu J.; Chiang J.; Iyer R.R.; Thompson E.; Kaneski C.R.; Xu D.S.; Yang C.; Chen M.; Hodes R.J.; Lonser R.R.; Brady R.O.; Zhuang Z.;
Proc. Natl. Acad. Sci. U.S.A. 107:21665-21670(2010)
Cited for: INTERACTION WITH TCP1; CHARACTERIZATION OF VARIANT GD1 SER-409; CHARACTERIZATION OF VARIANT GD2 SER-409 AND PRO-483;

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;

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;

The molecular characterization of Gaucher disease in South Africa.
Morar B.; Lane A.B.;
Clin. Genet. 50:78-84(1996)
Cited for: VARIANTS GD SER-409; LEU-426; LEU-433 AND PRO-483;

Identification of two novel and four uncommon missense mutations among Chinese Gaucher disease patients.
Choy F.Y.M.; Humphries M.L.; Shi H.;
Am. J. Med. Genet. 71:172-178(1997)
Cited for: VARIANTS GD VAL-76; GLU-85; TRP-87; TRP-159; SER-227; ILE-252 AND PRO-483;

Mutation prevalence among 47 unrelated Japanese patients with Gaucher disease: identification of four novel mutations.
Ida H.; Rennert O.M.; Kawame H.; Maekawa K.; Eto Y.;
J. Inherit. Metab. Dis. 20:67-73(1997)
Cited for: VARIANTS GD VAL-228; ILE-252; GLY-405; HIS-448; GLN-452; PRO-483 AND CYS-535;

A novel complex allele and two new point mutations in type 2 (acute neuronopathic) Gaucher disease.
Sinclair G.; Choy F.Y.M.; Humphries L.;
Blood Cells Mol. Dis. 24:420-427(1998)
Cited for: VARIANTS GD2 LYS-80; CYS-170 AND PRO-483;

Glucocerebrosidase mutations among Chinese neuronopathic and non-neuronopathic Gaucher disease patients.
Choy F.Y.M.; Wong K.; Shi H.P.;
Am. J. Med. Genet. 84:484-486(1999)
Cited for: VARIANTS GD ARG-241; CYS-244; ILE-252; HIS-448 AND PRO-483;

Detection of three rare (G377S, T134P and 1451delAC), and two novel mutations (G195W and Rec[1263del55;1342G>C]] in Spanish Gaucher disease patients.
Sarria A.J.; Giraldo P.; Perez-Calvo J.I.; Pocovi M.;
Hum. Mutat. 14:88-88(1999)
Cited for: VARIANTS GD PRO-173; TRP-234; SER-409; SER-416; HIS-448 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 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;

Identification and functional characterization of five novel mutant alleles in 58 Italian patients with Gaucher disease type 1.
Miocic S.; Filocamo M.; Dominissini S.; Montalvo A.L.; Vlahovicek K.; Deganuto M.; Mazzotti R.; Cariati R.; Bembi B.; Pittis M.G.;
Hum. Mutat. 25:100-100(2005)
Cited for: VARIANTS GD1 ASN-63; SER-158; TRP-159; CYS-170; LEU-221; GLU-230; ARG-241; GLN-294; CYS-324; SER-409; ASN-438; LEU-440; HIS-448; CYS-457; ASP-460; PRO-483 AND ARG-490; CHARACTERIZATION OF VARIANTS GD1 ASN-63; SER-158; LEU-221; GLU-230 AND ASP-460;

Glucocerebrosidase mutations and risk of Parkinson disease in Chinese patients.
Tan E.K.; Tong J.; Fook-Chong S.; Yih Y.; Wong M.C.; Pavanni R.; Zhao Y.;
Arch. Neurol. 64:1056-1058(2007)
Cited for: INVOLVEMENT OF VARIANT GD PRO-483 IN SUSCEPTIBILITY TO PARKINSON DISEASE;

Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders.
Mata I.F.; Samii A.; Schneer S.H.; Roberts J.W.; Griffith A.; Leis B.C.; Schellenberg G.D.; Sidransky E.; Bird T.D.; Leverenz J.B.; Tsuang D.; Zabetian C.P.;
Arch. Neurol. 65:379-382(2008)
Cited for: INVOLVEMENT OF VARIANTS GD SER-409 AND PRO-483 IN SUSCEPTIBILITY TO PARKINSON DISEASE;

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;

Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease.
Sidransky E.; Nalls M.A.; Aasly J.O.; Aharon-Peretz J.; Annesi G.; Barbosa E.R.; Bar-Shira A.; Berg D.; Bras J.; Brice A.; Chen C.M.; Clark L.N.; Condroyer C.; De Marco E.V.; Durr A.; Eblan M.J.; Fahn S.; Farrer M.J.; Fung H.C.; Gan-Or Z.; Gasser T.; Gershoni-Baruch R.; Giladi N.; Griffith A.; Gurevich T.; Januario C.; Kropp P.; Lang A.E.; Lee-Chen G.J.; Lesage S.; Marder K.; Mata I.F.; Mirelman A.; Mitsui J.; Mizuta I.; Nicoletti G.; Oliveira C.; Ottman R.; Orr-Urtreger A.; Pereira L.V.; Quattrone A.; Rogaeva E.; Rolfs A.; Rosenbaum H.; Rozenberg R.; Samii A.; Samaddar T.; Schulte C.; Sharma M.; Singleton A.; Spitz M.; Tan E.K.; Tayebi N.; Toda T.; Troiano A.R.; Tsuji S.; Wittstock M.; Wolfsberg T.G.; Wu Y.R.; Zabetian C.P.; Zhao Y.; Ziegler S.G.;
N. Engl. J. Med. 361:1651-1661(2009)
Cited for: INVOLVEMENT OF VARIANTS GD SER-409 AND PRO-483 IN SUSCEPTIBILITY TO PARKINSON DISEASE;

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.