UniProtKB/SwissProt variant VAR

Variant information

Variant position:

54

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 Glutamine (Q) to Proline (P) at position 54 (Q54P, p.Gln54Pro).

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 (Q) to medium size and hydrophobic (P)

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:

Glycogen storage disease 1A (GSD1A) [MIM:232200]: A metabolic disorder characterized by impairment of terminal steps of glycogenolysis and gluconeogenesis. Patients manifest a wide range of clinical symptoms and biochemical abnormalities, including hypoglycemia, severe hepatomegaly due to excessive accumulation of glycogen, kidney enlargement, growth retardation, lactic acidemia, hyperlipidemia, and hyperuricemia. {ECO:0000269|PubMed:10070617, ECO:0000269|PubMed:10094563, ECO:0000269|PubMed:10447271, ECO:0000269|PubMed:10612834, ECO:0000269|PubMed:10738005, ECO:0000269|PubMed:10748407, ECO:0000269|PubMed:10874313, ECO:0000269|PubMed:10960498, ECO:0000269|PubMed:11058903, ECO:0000269|PubMed:11058910, ECO:0000269|PubMed:12373566, ECO:0000269|PubMed:15151508, ECO:0000269|PubMed:15316959, ECO:0000269|PubMed:15542400, ECO:0000269|PubMed:7573034, ECO:0000269|PubMed:7623438, ECO:0000269|PubMed:7655466, ECO:0000269|PubMed:8182131, ECO:0000269|PubMed:8733042, ECO:0000269|PubMed:9001800, ECO:0000269|PubMed:9332655, ECO:0000269|PubMed:9506659, ECO:0000269|PubMed:9700612, ECO:0000269|PubMed:9700613}. 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 GSD1A.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1057517008 [ dbSNP | Ensembl ]

Sequence information

Variant position:

54

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

Protein sequence length:

357

The length of the canonical sequence.

Location on the sequence:

SVIADLRNAFYVLFPIWFHL Q EAVGIKLLWVAVIGDWLNLV

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                         SVIADLRNAFYVLFPIWFHLQEAVGIKLLWVAVIGDWLNLV

                              SVIADLRNAFYVLFPIWFHLREAVGIKLLWVAVIGDWLNLV

Mouse                         SVIADLRNAFYVLFPIWFHLKETVGINLLWVAVVGDWFNLV

Rat                           SVIADLRNAFYVLFPIWFHIQETVGINLLWVAVVGDWFNLV

Bovine                        SVIADLRNAFYVLFPIWFHLREAVGIKLLWVAVIGDWLNLV

Cat                           SVIADLRNAFYVLFPIWFHLREAVGIKLLWVAVIGDWLNLV

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	1 – 357	Glucose-6-phosphatase
Topological domain	50 – 60	Cytoplasmic
Mutagenesis	52 – 52	H -> A. Partial loss of catalytic activity.

Literature citations

Identification of three novel mutations (Q54P, W70X and T108I) in the glucose-6-phosphatase gene of patients with glycogen storage disease type Ia.
Trioche P.; Francoual J.; Chalas J.; Capel L.; Bernard O.; Labrune P.;
Hum. Mutat. 14:91-91(1999)
Cited for: VARIANTS GSD1A PRO-54 AND ILE-108;

Genetic heterogeneity of glycogen storage disease type Ia in France: a study of 48 patients.
Trioche P.; Francoual J.; Chalas J.; Capel L.; Lindenbaum A.; Odievre M.; Labrune P.;
Hum. Mutat. 16:444-444(2000)
Cited for: VARIANTS GSD1A ARG-5; VAL-38; PRO-54; CYS-83; ILE-108; LYS-110; ILE-111; GLU-184; ARG-188; THR-241; ARG-270; VAL-270; LEU-322; PHE-327 DEL AND PHE-338;

Glycogen storage disease type Ia in Argentina: two novel glucose-6-phosphatase mutations affecting protein stability.
Angaroni C.J.; de Kremer R.D.; Argarana C.E.; Paschini-Capra A.E.; Giner-Ayala A.N.; Pezza R.J.; Pan C.-J.; Chou J.Y.;
Mol. Genet. Metab. 83:276-279(2004)
Cited for: VARIANTS GSD1A ARG-16; PRO-54; CYS-83 AND CYS-209; CHARACTERIZATION OF VARIANTS GSD1A ARG-16 AND CYS-209;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35575: Variant p.Gln54Pro