UniProtKB/Swiss-Prot P04062: Variant p.Leu483Pro

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 483 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 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, GD2 and GD3; risk factor for Parkinson disease; gene conversion; alters protein stability; increased proteasomal degradation; decreased protein abundance; very low glucosylceramide catabolic process; severe decrease of glucosylceramidase activity; 3% of normal activity when expressed in a heterologous system. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs421016 [ dbSNP | Ensembl ]

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.
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.
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; Characterization of mutations in Gaucher patients by cDNA cloning.
Wigderson M.; Firon N.; Horowitz Z.; Wilder S.; Frishberg Y.; Reiner O.; Horowitz M.;
Am. J. Hum. Genet. 44:365-377(1989)
Cited for: VARIANTS GD2 ARG-454 AND PRO-483; CHARACTERIZATION OF VARIANTS GD2 ARG-454 AND PRO-483; 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; Gaucher disease: functional expression of the normal glucocerebrosidase and Gaucher T1366G and G1604A alleles in Baculovirus-transfected Spodoptera frugiperda cells.
Choy F.Y.; Wei C.; Levin D.;
Am. J. Med. Genet. 65:184-189(1996)
Cited for: CHARACTERIZATION OF VARIANTS GD1 SER-409; VAL-456 AND HIS-535; CHARACTERIZATION OF VARIANT GD2 PRO-483; 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; 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; Mutation analysis of Gaucher disease patients from Argentina: high prevalence of the RecNciI mutation.
Cormand B.; Harboe T.L.; Gort L.; Campoy C.; Blanco M.; Chamoles N.; Chabas A.; Vilageliu L.; Grinberg D.;
Am. J. Med. Genet. 80:343-351(1998)
Cited for: VARIANTS GD1 TRP-87; TRP-159; SER-200; ARG-241; ASP-304; CYS-324; SER-409; ASN-438; ILE-450 AND PRO-483; VARIANT GD2 HIS-448; 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: VARIANT GD1 CYS-244; VARIANTS GD2 ILE-252 AND PRO-483; VARIANTS GD3 ARG-241; 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 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; Novel point mutation (W184R) in neonatal type 2 Gaucher disease.
Choy F.Y.; Wong K.; Vallance H.D.; Baldwin V.;
Pediatr. Dev. Pathol. 3:180-183(2000)
Cited for: VARIANTS GD2 ARG-223 AND PRO-483; 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; 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; ASP-460 AND ARG-490; 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; Use of a multiplex ligation-dependent probe amplification method for the detection of deletions/duplications in the GBA1 gene in Gaucher disease patients.
Basgalupp S.P.; Siebert M.; Vairo F.P.E.; Chami A.M.; Pinto L.L.C.; Carvalho G.D.S.; Schwartz I.V.D.;
Blood Cells Mol. Dis. 68:17-20(2018)
Cited for: VARIANT GD2 ARG-350; VARIANTS GD1 SER-409; SER-416; ARG-483; PRO-483 AND PRO-495; Gaucher disease: Biochemical and molecular findings in 141 patients diagnosed in Greece.
Dimitriou E.; Moraitou M.; Cozar M.; Serra-Vinardell J.; Vilageliu L.; Grinberg D.; Mavridou I.; Michelakakis H.;
Mol. Genet. Metab. Rep. 24:100614-100614(2020)
Cited for: VARIANTS GD1 GLN-87; LEU-120; HIS-155; TRP-159; SER-174; PRO-214; ARG-223; ARG-241; ILE-252; ILE-270; GLN-294; ASN-322; VAL-348; ARG-350; SER-409; HIS-448; PRO-483; TYR-501; LYS-521 AND CYS-535; VARIANTS GD2 TRP-159; ARG-241; GLN-294; HIS-448 AND PRO-483; VARIANTS GD3 CYS-147; GLN-294; HIS-448 AND PRO-483;