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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q12879: Variant p.Ala548Thr

Glutamate receptor ionotropic, NMDA 2A
Gene: GRIN2A
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Variant information Variant position: help 548 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 Alanine (A) to Threonine (T) at position 548 (A548T, p.Ala548Thr). 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 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: help 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: help In FESD; no effect on localization to the cell membrane; loss of glutamate-gated calcium ion channel activity. Any additional useful information about the variant.


Sequence information Variant position: help 548 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 FVETGISVMVSRSNGTVSPS A FLEPFSASVWVMMFVMLLIV 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                         FVETGISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLIV

Chimpanzee                    FVETGISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLIV

Mouse                         FVETGISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLIV

Rat                           FVETGISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLIV

Xenopus laevis                FVETGISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLLV

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 23 – 555 Extracellular
Glycosylation 541 – 541 N-linked (GlcNAc...) asparagine
Mutagenesis 552 – 552 P -> A. Changed glutamate-gated calcium ion channel activity characterized by increased desensitization.
Mutagenesis 552 – 552 P -> G. Changed glutamate-gated calcium ion channel activity characterized by accelerated response activation time and increased desensitization.
Mutagenesis 552 – 552 P -> I. Changed glutamate-gated calcium ion channel activity characterized by increased desensitization.
Mutagenesis 552 – 552 P -> K. Changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency with delay in rise time and slower deactivation time course.
Mutagenesis 552 – 552 P -> L. No effect on localization to the cell membrane. Changed glutamate-gated calcium ion channel activity characterized by increased desensitization.
Mutagenesis 552 – 552 P -> Q. No effect on localization to the cell membrane. Changed glutamate-gated calcium ion channel activity characterized by decreased response amplitude and changed desensitization without effect on response rise time or deactivation time course.



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; Molecular mechanism of disease-associated mutations in the pre-M1 helix of NMDA receptors and potential rescue pharmacology.
Ogden K.K.; Chen W.; Swanger S.A.; McDaniel M.J.; Fan L.Z.; Hu C.; Tankovic A.; Kusumoto H.; Kosobucki G.J.; Schulien A.J.; Su Z.; Pecha J.; Bhattacharya S.; Petrovski S.; Cohen A.E.; Aizenman E.; Traynelis S.F.; Yuan H.;
PLoS Genet. 13:E1006536-E1006536(2017)
Cited for: CHARACTERIZATION OF VARIANTS FESD THR-548 AND ARG-552; MUTAGENESIS OF PRO-552;
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.