UniProtKB/SwissProt variant VAR

Variant information

Variant position:

34

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 34 (N34S, p.Asn34Ser).

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:

GLUT1 deficiency syndrome 1 (GLUT1DS1) [MIM:606777]: A neurologic disorder showing wide phenotypic variability. The most severe 'classic' phenotype comprises infantile-onset epileptic encephalopathy associated with delayed development, acquired microcephaly, motor incoordination, and spasticity. Onset of seizures, usually characterized by apneic episodes, staring spells, and episodic eye movements, occurs within the first 4 months of life. Other paroxysmal findings include intermittent ataxia, confusion, lethargy, sleep disturbance, and headache. Varying degrees of cognitive impairment can occur, ranging from learning disabilities to severe mental retardation. {ECO:0000269|PubMed:10227690, ECO:0000269|PubMed:10980529, ECO:0000269|PubMed:11136715, ECO:0000269|PubMed:11603379, ECO:0000269|PubMed:12325075, ECO:0000269|PubMed:15622525, ECO:0000269|PubMed:19901175, ECO:0000269|PubMed:20129935, ECO:0000269|PubMed:20221955, ECO:0000269|PubMed:20574033, ECO:0000269|PubMed:24847886, ECO:0000269|PubMed:25982116, ECO:0000269|PubMed:30197081}. 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 GLUT1DS1; 55% of wild-type glucose uptake activity.

Any additional useful information about the variant.

Sequence information

Variant position:

34

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

Protein sequence length:

492

The length of the canonical sequence.

Location on the sequence:

LAVGGAVLGSLQFGYNTGVI N APQKVIEEFYNQTWVHRYGE

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                         LAVGGAVLGSLQFGYNTGVINAPQKVIEEFYNQTWVHRYGE

Mouse                         LAVGGAVLGSLQFGYNTGVINAPQKVIEEFYNQTWNHRYGE

Rat                           LAVGGAVLGSLQFGYNTGVINAPQKVIEEFYNQTWNHRYGE

Pig                           LAVGGAVLGSLQFGYNTGVINAPQKVIEEFYNQTWLHRYGE

Bovine                        LAVGGAVLGSLQFGYNTGVINAPQKVIEEFYNQTWVQRYGE

Rabbit                        LAVGGAVLGSLQFGYNTGVINAPQKVIEEFYNQTWIHRYGE

Sheep                         LAVGGAVLGSLQFGYNTGVINAPQKVIEEFYNQTWMQRYGE

Chicken                       LAVGGAVLGSLQFGYNTGVINRPQKVIEDFYNHTWLYRYEE

Drosophila                    YSIFSAVLGMLQFGYNTGVINAPEKNIENFMKDVYKDRYGE

Baker's yeast                 -----------------MSSNNRKKLL--------------

Fission yeast                 ---------------------MRKKVL--------------

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 – 492	Solute carrier family 2, facilitated glucose transporter member 1
Topological domain	34 – 66	Extracellular
Glycosylation	45 – 45	N-linked (GlcNAc...) asparagine
Mutagenesis	45 – 45	N -> T. Loss of glycosylation site.

Literature citations

Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects.
Wang D.; Pascual J.M.; Yang H.; Engelstad K.; Jhung S.; Sun R.P.; De Vivo D.C.;
Ann. Neurol. 57:111-118(2005)
Cited for: VARIANTS GLUT1DS1 SER-34; HIS-126; SER-130; CYS-153; LEU-169 DEL; MET-295 AND TRP-333; CHARACTERIZATION OF VARIANTS GLUT1 DEFICIENCY SER-34; HIS-126; SER-130; CYS-153; LEU-169 DEL; MET-295 AND TRP-333;

UniProtKB/Swiss-Prot P11166: Variant p.Asn34Ser