UniProtKB/Swiss-Prot P04062: Variant p.Asn409Ser

Gene: GBA
Chromosomal location: 1q21
Variant information

Variant position:  409
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Asparagine (N) to Serine (S) at position 409 (N409S, p.Asn409Ser).
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 medium size and polar (N) to small size and polar (S)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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

Involvement in disease:  Gaucher disease 1 (GD1) [MIM:230800]: A form of Gaucher disease characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved. {ECO:0000269|PubMed:10206680, ECO:0000269|PubMed:10340647, ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:8889591, ECO:0000269|Ref.14}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In GD1; common mutation; associated with susceptibility to Parkinson disease; alters interaction with saposin-C; mild.
Any additional useful information about the variant.

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

Sequence information

Variant position:  409
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  536
The length of the canonical sequence.

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.






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.

Chain 40 – 536 Glucosylceramidase
Helix 396 – 411

Literature citations

Genetic heterogeneity in type 1 Gaucher disease: multiple genotypes in Ashkenazic and non-Ashkenazic individuals.
Tsuji S.; Martin B.M.; Barranger J.A.; Stubblefield B.K.; LaMarca M.E.; Ginns E.I.;

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;

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; CHARACTERIZATION OF VARIANTS GD SER-55; GLN-87; ASN-118; GLN-159; 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 AND PRO-502; MUTAGENESIS OF CYS-43; CYS-57 AND CYS-62;

Y418C: a novel mutation in exon 9 of the glucocerebrosidase gene of a patient with Gaucher disease creates a new Bgl I site.
Tuteja R.; Tuteja N.; Lilliu F.; Bembi B.; Galanello R.; Cao A.; Baralle F.E.;
Hum. Genet. 94:314-315(1994)
Cited for: VARIANTS GD SER-409 AND CYS-457;

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 and expression of acid beta-glucosidase mutations causing severe type 1 and neurologic type 2 Gaucher disease in non-Jewish patients.
Grace M.E.; Desnick R.J.; Pastores G.M.;
J. Clin. Invest. 99:2530-2537(1997)
Cited for: VARIANTS GD TRP-87; GLU-234; ARG-241; ILE-252; ASN-310; LEU-391 AND SER-409;

A novel mutation (V191G) in a German-British type 1 Gaucher disease patient.
Choy F.Y.M.; Humphries M.L.; Ben-Yoseph Y.;
Hum. Mutat. 11:411-412(1998)
Cited for: VARIANTS GD1 GLY-230 AND SER-409;

Type 1 Gaucher disease presenting with extensive mandibular lytic lesions: identification and expression of a novel acid beta-glucosidase mutation.
Wasserstein M.P.; Martignetti J.A.; Zeitlin R.; Lumerman H.; Solomon M.; Grace M.E.; Desnick R.J.;
Am. J. Med. Genet. 84:334-339(1999)
Cited for: VARIANTS GD1 SER-409 AND LEU-440;

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;

The N370S (Asn370->Ser) mutation affects the capacity of glucosylceramidase to interact with anionic phospholipid-containing membranes and saposin C.
Salvioli R.; Tatti M.; Scarpa S.; Moavero S.M.; Ciaffoni F.; Felicetti F.; Kaneski C.R.; Brady R.O.; Vaccaro A.M.;
Biochem. J. 390:95-103(2005)

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 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)

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)

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.