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UniProtKB/Swiss-Prot Q12879: Variant p.Ala727Thr

Glutamate receptor ionotropic, NMDA 2A
Gene: GRIN2A
Variant information

Variant position:  727
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Alanine (A) to Threonine (T) at position 727 (A727T, p.Ala727Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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

Variant description:  In FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency and decreased open probability.
Any additional useful information about the variant.

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

Sequence information

Variant position:  727
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1464
The length of the canonical sequence.

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.






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.

Chain 23 – 1464 Glutamate receptor ionotropic, NMDA 2A
Topological domain 646 – 816 Extracellular
Beta strand 726 – 731

Literature citations

Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes.
Lemke J.R.; Lal D.; Reinthaler E.M.; Steiner I.; Nothnagel M.; Alber M.; Geider K.; Laube B.; Schwake M.; Finsterwalder K.; Franke A.; Schilhabel M.; Jahn J.A.; Muhle H.; Boor R.; Van Paesschen W.; Caraballo R.; Fejerman N.; Weckhuysen S.; De Jonghe P.; Larsen J.; Moller R.S.; Hjalgrim H.; Addis L.; Tang S.; Hughes E.; Pal D.K.; Veri K.; Vaher U.; Talvik T.; Dimova P.; Guerrero Lopez R.; Serratosa J.M.; Linnankivi T.; Lehesjoki A.E.; Ruf S.; Wolff M.; Buerki S.; Wohlrab G.; Kroell J.; Datta A.N.; Fiedler B.; Kurlemann G.; Kluger G.; Hahn A.; Haberlandt D.E.; Kutzer C.; Sperner J.; Becker F.; Weber Y.G.; Feucht M.; Steinbock H.; Neophythou B.; Ronen G.M.; Gruber-Sedlmayr U.; Geldner J.; Harvey R.J.; Hoffmann P.; Herms S.; Altmuller J.; Toliat M.R.; Thiele H.; Nurnberg P.; Wilhelm C.; Stephani U.; Helbig I.; Lerche H.; Zimprich F.; Neubauer B.A.; Biskup S.; von Spiczak S.;
Nat. Genet. 45:1067-1072(2013)
Cited for: VARIANTS FESD ARG-79; TYR-231; VAL-243; VAL-290; TRP-370; ARG-436; SER-547 DEL; SER-699; VAL-705; LYS-714; THR-727; LEU-734; GLU-772; THR-814; PHE-904 AND SER-976; VARIANT ILE-183; CHARACTERIZATION OF VARIANT FESD VAL-243;

Mechanistic insight into NMDA receptor dysregulation by rare variants in the GluN2A and GluN2B agonist binding domains.
Swanger S.A.; Chen W.; Wells G.; Burger P.B.; Tankovic A.; Bhattacharya S.; Strong K.L.; Hu C.; Kusumoto H.; Zhang J.; Adams D.R.; Millichap J.J.; Petrovski S.; Traynelis S.F.; Yuan H.;
Am. J. Hum. Genet. 99:1261-1280(2016)
Cited for: VARIANTS FESD ALA-506 AND GLY-685; CHARACTERIZATION OF VARIANT FESD ARG-436; ARG-483; TRP-504; ALA-506; HIS-518; MET-531; ASN-669; GLY-685; THR-694; SER-699; VAL-705; LYS-714; THR-716; THR-727; ASN-731; LEU-734; GLU-772; CHARACTERIZATION OF VARIANT MET-452;

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.