UniProtKB/SwissProt variant VAR

Variant information

Variant position:

243

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 Glutamate (E) to Valine (V) at position 243 (E243V, p.Glu243Val).

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 (E) to medium size and hydrophobic (V)

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:

Epilepsy, idiopathic generalized 12 (EIG12) [MIM:614847]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. In some EIG12 patients seizures may remit with age. {ECO:0000269|PubMed:19798636, ECO:0000269|PubMed:22282645, ECO:0000269|PubMed:23280796, ECO:0000269|PubMed:25982116}. Note=Disease susceptibility is associated with variations 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 EIG12; decreased glucose transport.

Any additional useful information about the variant.

Sequence information

Variant position:

243

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:

RAKSVLKKLRGTADVTHDLQ E MKEESRQMMREKKVTILELF

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                         RAKSVLKKLRGTADVTHDLQEMKEESRQMMREKKVTILELF

Mouse                         RAKSVLKKLRGTADVTRDLQEMKEEGRQMMREKKVTILELF

Rat                           RAKSVLKKLRGTADVTRDLQEMKEEGRQMMREKKVTILELF

Pig                           RAKSVLKKLRGTADVTRDLQEMKEESRQMMREKKVTILELF

Bovine                        RAKSVLKKLRGTADVTRDLQEMKEESRQMMREKKVTILELF

Rabbit                        RAKSVLKKLRGNADVTRDLQEMKEESRQMMREKKVTILELF

Sheep                         RAKSVLKKLRGTADVTRDLQEMKEESRQMMREKKVTILELF

Chicken                       KAKSVLKKLRGTTDVSSDLQEMKEESRQMMREKKVTIMELF

Drosophila                    EARKALRRLRASGSVEEDIEEMRAEERAQQSESHISTMELI

Baker's yeast                 ------------------MDLVQLDKREELFQ---------

Fission yeast                 ------------------MDLVQEDLRDLVFEER-------

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	207 – 271	Cytoplasmic
Modified residue	226 – 226	Phosphoserine; by PKC/PRKCB
Mutagenesis	226 – 226	S -> A. Abolishes phosphorylation by PKA, leading to impaired response to TPA.
Helix	238 – 253

Literature citations

Glucose transporter 1 deficiency in the idiopathic generalized epilepsies.
Arsov T.; Mullen S.A.; Rogers S.; Phillips A.M.; Lawrence K.M.; Damiano J.A.; Goldberg-Stern H.; Afawi Z.; Kivity S.; Trager C.; Petrou S.; Berkovic S.F.; Scheffer I.E.;
Ann. Neurol. 72:807-815(2012)
Cited for: VARIANTS EIG12 HIS-51; MET-60; THR-77; ALA-149; SER-218; GLN-223; VAL-243; SER-411 AND TRP-458; CHARACTERIZATION OF VARIANTS EIG12 MET-60; THR-77; SER-218; GLN-223; VAL-243; SER-411 AND TRP-458;

UniProtKB/Swiss-Prot P11166: Variant p.Glu243Val