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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q12879: Variant p.Phe652Val

Glutamate receptor ionotropic, NMDA 2A
Gene: GRIN2A
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Variant information Variant position: help 652 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Phenylalanine (F) to Valine (V) at position 652 (F652V, p.Phe652Val). 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: help Change from large size and aromatic (F) to medium size and hydrophobic (V) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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
Variant description: help In FESD; likely pathogenic; results in increased agonist potency and channel activation at lower glutamate and glycine concentrations compared to wild type channels; results in substantial alterations of channel gating properties and affects duration of channel open and closed states. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 652 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1464 The length of the canonical sequence.
Location on the sequence: help SVWAFFAVIFLASYTANLAA F MIQEEFVDQVTGLSDKKFQR 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         SVWAFFAVIFLASYTANLAAFMIQEEFVDQVTGLSDKKFQR

Chimpanzee                    SVWAFFAVIFLASYTANLAAFMIQEEFVDQVTGLSDKKFQR

Mouse                         SVWAFFAVIFLASYTANLAAFMIQEEFVDQVTGLSDKKFQR

Rat                           SVWAFFAVIFLASYTANLAAFMIQEEFVDQVTGLSDKKFQR

Xenopus laevis                SIWAFFAVIFLASYTANLAAFMIQEEFVDQVTGLSDNKFQR
Sequence annotation in neighborhood: help 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 23 – 1464 Glutamate receptor ionotropic, NMDA 2A
Topological domain 646 – 816 Extracellular
Mutagenesis 632 – 632 S -> F. No effect on localization to the cell membrane. No effect on agonist potency and channel activation by glutamate and glycine.
Mutagenesis 646 – 646 T -> R. No effect on localization to the cell membrane. Results in increased glycine potency and channel activation at lower agonist concentrations.
Helix 625 – 654



Literature citations
GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction.
Lesca G.; Rudolf G.; Bruneau N.; Lozovaya N.; Labalme A.; Boutry-Kryza N.; Salmi M.; Tsintsadze T.; Addis L.; Motte J.; Wright S.; Tsintsadze V.; Michel A.; Doummar D.; Lascelles K.; Strug L.; Waters P.; de Bellescize J.; Vrielynck P.; de Saint Martin A.; Ville D.; Ryvlin P.; Arzimanoglou A.; Hirsch E.; Vincent A.; Pal D.; Burnashev N.; Sanlaville D.; Szepetowski P.;
Nat. Genet. 45:1061-1066(2013)
Cited for: VARIANTS FESD SER-184; SER-295; ARG-483; TRP-504; HIS-518; THR-548; VAL-652; ASN-669; THR-694; THR-716; ASN-731; ASN-933 AND ASN-1251; VARIANT GLY-1276; CHARACTERIZATION OF VARIANTS FESD HIS-518 AND VAL-652; Complex functional phenotypes of NMDA receptor disease variants.
Iacobucci G.J.; Liu B.; Wen H.; Sincox B.; Zheng W.; Popescu G.K.;
Mol. Psychiatry 27:5113-5123(2022)
Cited for: CHARACTERIZATION OF VARIANTS ARG-552 AND VAL-652; De novo GRIN variants in M3 helix associated with neurological disorders control channel gating of NMDA receptor.
Xu Y.; Song R.; Perszyk R.E.; Chen W.; Kim S.; Park K.L.; Allen J.P.; Nocilla K.A.; Zhang J.; Xiang Wei W.; Tankovic A.; McDaniels E.D.; Sheikh R.; Mizu R.K.; Karamchandani M.M.; Hu C.; Kusumoto H.; Pecha J.; Cappuccio G.; Gaitanis J.; Sullivan J.; Shashi V.; Petrovski S.; Jauss R.T.; Lee H.K.; Bozarth X.; Lynch D.R.; Helbig I.; Pierson T.M.; Boerkoel C.F.; Myers S.J.; Lemke J.R.; Benke T.A.; Yuan H.; Traynelis S.F.;
Cell. Mol. Life Sci. 81:153-153(2024)
Cited for: VARIANTS FESD THR-635; ILE-639; ARG-642; ALA-646; SER-648; SER-650; VAL-652 AND VAL-653; CHARACTERIZATION OF VARIANTS FESD THR-635; ILE-639; ARG-642; GLY-644; ALA-646; SER-648; VAL-649; SER-650; ILE-653; VAL-653 AND THR-654; VARIANT MET-642; CHARACTERIZATION OF VARIANTS MET-642 AND ASP-643; MUTAGENESIS OF SER-632 AND THR-646;
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.