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UniProtKB/Swiss-Prot P10253: Variant p.Tyr191Cys

Lysosomal alpha-glucosidase
Gene: GAA
Chromosomal location: 17q25.2-q25.3
Variant information

Variant position:  191
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 Tyrosine (Y) to Cysteine (C) at position 191 (Y191C, p.Tyr191Cys).
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 aromatic (Y) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Glycogen storage disease 2 (GSD2) [MIM:232300]: A metabolic disorder with a broad clinical spectrum. The severe infantile form, or Pompe disease, presents at birth with massive accumulation of glycogen in muscle, heart and liver. Cardiomyopathy and muscular hypotonia are the cardinal features of this form whose life expectancy is less than two years. The juvenile and adult forms present as limb-girdle muscular dystrophy beginning in the lower limbs. Final outcome depends on respiratory muscle failure. Patients with the adult form can be free of clinical symptoms for most of their life but finally develop a slowly progressive myopathy. {ECO:0000269|PubMed:10189220, ECO:0000269|PubMed:10206684, ECO:0000269|PubMed:10338092, ECO:0000269|PubMed:10737124, ECO:0000269|PubMed:11071489, ECO:0000269|PubMed:11738358, ECO:0000269|PubMed:12601120, ECO:0000269|PubMed:12923862, ECO:0000269|PubMed:14643388, ECO:0000269|PubMed:14695532, ECO:0000269|PubMed:14972326, ECO:0000269|PubMed:15145338, ECO:0000269|PubMed:15668445, ECO:0000269|PubMed:16433701, ECO:0000269|PubMed:1652892, ECO:0000269|PubMed:16782080, ECO:0000269|PubMed:1684505, ECO:0000269|PubMed:16917947, ECO:0000269|PubMed:17643989, ECO:0000269|PubMed:18425781, ECO:0000269|PubMed:18429042, ECO:0000269|PubMed:1898413, ECO:0000269|PubMed:19588081, ECO:0000269|PubMed:20080426, ECO:0000269|PubMed:20350966, ECO:0000269|PubMed:21109266, ECO:0000269|PubMed:22644586, ECO:0000269|PubMed:22676651, ECO:0000269|PubMed:25681614, ECO:0000269|PubMed:7695647, ECO:0000269|PubMed:7717400, ECO:0000269|PubMed:7866409, ECO:0000269|PubMed:7881422, ECO:0000269|PubMed:7981676, ECO:0000269|PubMed:8094613, ECO:0000269|PubMed:8401535, ECO:0000269|PubMed:8834250, ECO:0000269|PubMed:9521422, ECO:0000269|PubMed:9535769, ECO:0000269|PubMed:9660056, ECO:0000269|Ref.5}. 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 GSD2; extremely low residual enzymatic activity.
Any additional useful information about the variant.

Sequence information

Variant position:  191
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  952
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 70 – 952 Lysosomal alpha-glucosidase
Chain 123 – 952 76 kDa lysosomal alpha-glucosidase

Literature citations

Molecular and functional characterization of eight novel GAA mutations in Italian infants with Pompe disease.
Pittis M.G.; Donnarumma M.; Montalvo A.L.E.; Dominissini S.; Kroos M.; Rosano C.; Stroppiano M.; Bianco M.G.; Donati M.A.; Parenti G.; D'Amico A.; Ciana G.; Di Rocco M.; Reuser A.; Bembi B.; Filocamo M.;
Hum. Mutat. 29:E27-E36(2008)
Cited for: VARIANTS GSD2 GLY-103; CYS-191; ARG-219; TRP-224; LYS-262; ARG-293; PRO-355; LEU-375; ARG-401; ASN-489; ALA-522; PRO-552; TYR-599; TRP-638; ARG-643 AND ASN-645; CHARACTERIZATION OF VARIANTS GSD2 CYS-191; LEU-375; ARG-401; ALA-522 AND TYR-599; FUNCTION; CATALYTIC ACTIVITY;

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.