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UniProtKB/Swiss-Prot P11166: Variant p.Arg212Cys

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

Variant position:  212
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 Cysteine (C) at position 212 (R212C, p.Arg212Cys).
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 polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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}. 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.

Involvement in disease:  Dystonia 9 (DYT9) [MIM:601042]: An autosomal dominant neurologic disorder characterized by childhood onset of paroxysmal choreoathetosis and progressive spastic paraplegia. Most patients show some degree of cognitive impairment. Other variable features may include seizures, migraine headaches, and ataxia. {ECO:0000269|PubMed:21832227}. 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 and DYT9.
Any additional useful information about the variant.

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



Sequence information

Variant position:  212
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:   IIFIPALLQCIVLPFCPESP  R FLLINRNEENRAKSVLKKLR
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                         IIFIPALLQCIVLPFCPESPRFLLINRNEENRAKSVLKKLR

Mouse                         VIFIPALLQCILLPFCPESPRFLLINRNEENRAKSVLKKLR

Rat                           VIFIPALLQCILLPFCPESPRFLLINRNEENRAKSVLKKLR

Pig                           VIFIPALLQCVLLPFCPESPRFLLINRNEENRAKSVLKKLR

Bovine                        VIFIPALLQCILLPFCPESPRFLLINRNEENRAKSVLKKLR

Rabbit                        VIFVPALLQCIVLPLCPESPRFLLINRNEENRAKSVLKKLR

Sheep                         VIFIPALLQCILLPFCPESPRFLLINRNEENRAKSVLKKLR

Chicken                       FIFVPALLQCIILPFAPESPRFLLINRNEENKAKSVLKKLR

Drosophila                    LAICPAILQLILLPVCPESPRYLLITKQWEEEARKALRRLR

Baker's yeast                 EIFAKALKQLRKYS--PDAKIFVLLHK--------------

Fission yeast                 VTFRNCLEATVANS--PQARVFCLIHK--------------

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 192 – 192 I -> C. Strongly decreases glucose transport.
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 211 – 215


Literature citations

Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder.
Leen W.G.; Klepper J.; Verbeek M.M.; Leferink M.; Hofste T.; van Engelen B.G.; Wevers R.A.; Arthur T.; Bahi-Buisson N.; Ballhausen D.; Bekhof J.; van Bogaert P.; Carrilho I.; Chabrol B.; Champion M.P.; Coldwell J.; Clayton P.; Donner E.; Evangeliou A.; Ebinger F.; Farrell K.; Forsyth R.J.; de Goede C.G.; Gross S.; Grunewald S.; Holthausen H.; Jayawant S.; Lachlan K.; Laugel V.; Leppig K.; Lim M.J.; Mancini G.; Marina A.D.; Martorell L.; McMenamin J.; Meuwissen M.E.; Mundy H.; Nilsson N.O.; Panzer A.; Poll-The B.T.; Rauscher C.; Rouselle C.M.; Sandvig I.; Scheffner T.; Sheridan E.; Simpson N.; Sykora P.; Tomlinson R.; Trounce J.; Webb D.; Weschke B.; Scheffer H.; Willemsen M.A.;
Brain 133:655-670(2010)
Cited for: VARIANTS GLUT1DS1 TYR-34; VAL-96; SER-130; VAL-155; CYS-212; HIS-212; TRP-223; MET-295; GLN-329; GLN-333; ASP-382; ASP-405 AND LEU-485; VARIANTS GLUT1DS2 TRP-93 AND HIS-153; VARIANT LEU-303;

Paroxysmal choreoathetosis/spasticity (DYT9) is caused by a GLUT1 defect.
Weber Y.G.; Kamm C.; Suls A.; Kempfle J.; Kotschet K.; Schule R.; Wuttke T.V.; Maljevic S.; Liebrich J.; Gasser T.; Ludolph A.C.; Van Paesschen W.; Schols L.; De Jonghe P.; Auburger G.; Lerche H.;
Neurology 77:959-964(2011)
Cited for: VARIANTS DYT9 CYS-126 AND CYS-212;

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.