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UniProtKB/Swiss-Prot P11166: Variant p.Arg223Pro

Solute carrier family 2, facilitated glucose transporter member 1
Gene: SLC2A1
Variant information

Variant position:  223
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 Arginine (R) to Proline (P) at position 223 (R223P, p.Arg223Pro).
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 basic (R) to medium size and hydrophobic (P)
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; mild phenotype; reduced transporter activity; impaired phosphorylation by PKC.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  223
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:   VLPFCPESPRFLLINRNEEN  R AKSVLKKLRGTADVTHDLQE
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                         VLPFCPESPRFLLINRNEENRAKSVLKKLRGTADVTHDLQE

Mouse                         LLPFCPESPRFLLINRNEENRAKSVLKKLRGTADVTRDLQE

Rat                           LLPFCPESPRFLLINRNEENRAKSVLKKLRGTADVTRDLQE

Pig                           LLPFCPESPRFLLINRNEENRAKSVLKKLRGTADVTRDLQE

Bovine                        LLPFCPESPRFLLINRNEENRAKSVLKKLRGTADVTRDLQE

Rabbit                        VLPLCPESPRFLLINRNEENRAKSVLKKLRGNADVTRDLQE

Sheep                         LLPFCPESPRFLLINRNEENRAKSVLKKLRGTADVTRDLQE

Chicken                       ILPFAPESPRFLLINRNEENKAKSVLKKLRGTTDVSSDLQE

Drosophila                    LLPVCPESPRYLLITKQWEEEARKALRRLRASGSVEEDIEE

Baker's yeast                 KYS--PDAKIFVLLHK----------------------MDL

Fission yeast                 ANS--PQARVFCLIHK----------------------MDL

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 – 492 Solute carrier family 2, facilitated glucose transporter member 1
Topological domain 207 – 271 Cytoplasmic
Modified residue 226 – 226 Phosphoserine; by PKC/PRKCB
Mutagenesis 204 – 204 L -> C. Abolishes glucose transport.
Mutagenesis 205 – 205 P -> C. Abolishes glucose transport.
Mutagenesis 226 – 226 S -> A. Abolishes phosphorylation by PKA, leading to impaired response to TPA.
Helix 221 – 232


Literature citations

A protein kinase C phosphorylation motif in GLUT1 affects glucose transport and is mutated in GLUT1 deficiency syndrome.
Lee E.E.; Ma J.; Sacharidou A.; Mi W.; Salato V.K.; Nguyen N.; Jiang Y.; Pascual J.M.; North P.E.; Shaul P.W.; Mettlen M.; Wang R.C.;
Mol. Cell 58:845-853(2015)
Cited for: FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; SUBCELLULAR LOCATION; PHOSPHORYLATION AT SER-226; MUTAGENESIS OF SER-226; CHARACTERIZATION OF VARIANTS EIG12 PRO-223 AND GLN-223; CHARACTERIZATION OF VARIANT GLUT1DS1 TRP-223;

Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1.
Suls A.; Mullen S.A.; Weber Y.G.; Verhaert K.; Ceulemans B.; Guerrini R.; Wuttke T.V.; Salvo-Vargas A.; Deprez L.; Claes L.R.; Jordanova A.; Berkovic S.F.; Lerche H.; De Jonghe P.; Scheffer I.E.;
Ann. Neurol. 66:415-419(2009)
Cited for: VARIANT EIG12 PRO-223; VARIANTS GLUT1DS2 CYS-126 AND LEU-324; CHARACTERIZATION OF VARIANT EIG12 PRO-223; CHARACTERIZATION OF VARIANTS GLUT1DS2 CYS-126 AND LEU-324;

Absence epilepsies with widely variable onset are a key feature of familial GLUT1 deficiency.
Mullen S.A.; Suls A.; De Jonghe P.; Berkovic S.F.; Scheffer I.E.;
Neurology 75:432-440(2010)
Cited for: VARIANTS GLUT1DS2 ILE-95; PRO-223; SER-314 AND LEU-324; VARIANTS GLUT1DS1 ASP-91 AND HIS-126;

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.