UniProtKB/Swiss-Prot P35573: Variant p.Gly1448Arg

Glycogen debranching enzyme
Gene: AGL
Chromosomal location: 1p21
Variant information

Variant position:  1448
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Glycine (G) to Arginine (R) at position 1448 (G1448R, p.Gly1448Arg).
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 glycine (G) to large size and basic (R)
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 3 (GSD3) [MIM:232400]: A metabolic disorder associated with an accumulation of abnormal glycogen with short outer chains. It is clinically characterized by hepatomegaly, hypoglycemia, short stature, and variable myopathy. Glycogen storage disease type 3 includes different forms: GSD type 3A patients lack glycogen debrancher enzyme activity in both liver and muscle, while GSD type 3B patients are enzyme-deficient in liver only. In rare cases, selective loss of only 1 of the 2 debranching activities, glucosidase or transferase, results in GSD type 3C or type 3D, respectively. 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 GSD3; deficient in ability to bind glycogen; unstable due to enhanced ubiquitination; forms aggresomes upon proteasome impairment.
Any additional useful information about the variant.



Sequence information

Variant position:  1448
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1532
The length of the canonical sequence.

Location on the sequence:   YDNALDNDNYNLAKGFNYHQ  G PEWLWPIGYFLRAKLYFSRL
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                         YDNALDNDNYNLAKGFNYHQGPEWLWPIGYFLRAKLYFSRL

Rabbit                        YDNALDNDNYNLAKGFNYHQGPEWLWPVGYFLRAKLYFSKL

Dog                           YDNALDNDNYNLAKGFNYHQGPEWLWPVGYFLRAKLYFSKL

Horse                         YDNALDNDNYNLAKGFNYHQGPEWLWPTGYFLRAKLYFSKL

Baker's yeast                 YNNGEDSDDFATSKGRNYHQGPEWVWLYGYFLRAFHHFHFK

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 1 – 1532 Glycogen debranching enzyme


Literature citations

A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori's disease.
Cheng A.; Zhang M.; Gentry M.S.; Worby C.A.; Dixon J.E.; Saltiel A.R.;
Genes Dev. 21:2399-2409(2007)
Cited for: UBIQUITINATION; CHARACTERIZATION OF VARIANT GSD3 ARG-1448; INTERACTION WITH NHLRC1; SUBCELLULAR LOCATION;

Glycogen storage disease type IIIa: first report of a causative missense mutation (G1448R) of the glycogen debranching enzyme gene found in a homozygous patient.
Okubo M.; Kanda F.; Horinishi A.; Takahashi K.; Okuda S.; Chihara K.; Murase T.;
Hum. Mutat. 14:542-543(1999)
Cited for: VARIANT GSD3 ARG-1448; VARIANT ARG-1115;

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.