UniProtKB/Swiss-Prot P04062: Variant p.Asp448His

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 448 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 Aspartate (D) to Histidine (H) at position 448 (D448H, p.Asp448His). 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 acidic (D) to medium size and polar (H) 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
Variant description: In GD1, GD2, GD3 and GD3C; associated in cis with Q-294 in some patients; at homozygosity it causes GD3C; also found in a patient with Parkinson disease; loss of glucosylceramidase activity; alters protein stability. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs1064651 [ dbSNP | Ensembl ]

Sequence information

Variant position: 448 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: GGPNWVRNFVDSPIIVDITK D TFYKQPMFYHLGHFSKFIPE 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
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; Comparison of RNase A, a chemical cleavage and GC-clamped denaturing gradient gel electrophoresis for the detection of mutations in exon 9 of the human acid beta-glucosidase gene.
Theophilus B.D.; Latham T.; Grabowski G.A.; Smith F.I.;
Nucleic Acids Res. 17:7707-7722(1989)
Cited for: VARIANTS GD1 LEU-433 AND HIS-448; VARIANTS GD3 LEU-433; HIS-448 AND VAL-448; Prevalent and rare mutations among Gaucher patients.
Eyal N.; Wilder S.; Horowitz M.;
Gene 96:277-283(1990)
Cited for: VARIANTS GD2 ARG-364 AND GLY-381; VARIANT GD1 HIS-448; 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's disease variant characterised by progressive calcification of heart valves and unique genotype.
Abrahamov A.; Elstein D.; Gross-Tsur V.; Farber B.; Glaser Y.; Hadas-Halpern I.; Ronen S.; Tafakjdi M.; Horowitz M.; Zimran A.;
Lancet 346:1000-1003(1995)
Cited for: VARIANT GD HIS-448; 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; D409H/D409H genotype in Gaucher-like disease.
Uyama E.; Uchino M.; Ida H.; Eto Y.; Owada M.;
J. Med. Genet. 34:175-175(1997)
Cited for: VARIANT GD3C HIS-448; 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; 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; Variant Gaucher disease characterized by dysmorphic features, absence of cardiovascular involvement, laryngospasm, and compound heterozygosity for a novel mutation (D409H/C16S).
Bodamer O.A.F.; Church H.J.; Cooper A.; Wraith J.E.; Scott C.R.; Scaglia F.;
Am. J. Med. Genet. 109:328-331(2002)
Cited for: VARIANTS GD SER-55 AND HIS-448; The identification of eight novel glucocerebrosidase (GBA) mutations in patients with Gaucher disease.
Orvisky E.; Park J.K.; Parker A.; Walker J.M.; Martin B.M.; Stubblefield B.K.; Uyama E.; Tayebi N.; Sidransky E.;
Hum. Mutat. 19:458-459(2002)
Cited for: VARIANT GD GLU-175; VARIANT GDPL LEU-290; VARIANTS GD1 PRO-201 AND SER-409; VARIANT GD2 GLU-237; VARIANTS GD3 CYS-244; SER-416; PHE-441 AND HIS-448; Analysis of the glucocerebrosidase gene and mutation profile in 144 Italian Gaucher patients.
Filocamo M.; Mazzotti R.; Stroppiano M.; Seri M.; Giona F.; Parenti G.; Regis S.; Corsolini F.; Zoboli S.; Gatti R.;
Hum. Mutat. 20:234-235(2002)
Cited for: VARIANTS GD1 THR-198; CYS-209; PRO-209; ARG-241; ILE-252; CYS-324; HIS-324; CYS-351; ASN-438; HIS-448; CYS-457; PRO-485 AND ARG-490; VARIANTS GD2 CYS-170; PRO-235; ARG-241; ARG-270 AND ILE-400; VARIANTS GD3 LEU-146; SER-227; ARG-241; ILE-252; CYS-324; GLY-392 AND HIS-448; Homozygosity for a non-pseudogene complex glucocerebrosidase allele as cause of an atypical neuronopathic form of Gaucher disease.
Filocamo M.; Grossi S.; Stroppiano M.; Tortori-Donati P.; Regis S.; Allegri A.; Di Rocco M.;
Am. J. Med. Genet. A 134A:95-96(2005)
Cited for: VARIANTS GD2 GLN-294 AND HIS-448; 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 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; 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; The molecular mechanism of Gaucher disease caused by compound heterozygous mutations in GBA1 gene.
Liu Q.; Shen Z.; Pan H.; Ma S.; Xiong F.; He F.;
Front. Pediatr. 11:1092645-1092645(2023)
Cited for: VARIANTS GD1 LEU-414 AND HIS-448;