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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q05586: Variant p.Asn650Lys

Glutamate receptor ionotropic, NMDA 1
Gene: GRIN1
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Variant information Variant position: help 650 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 Asparagine (N) to Lysine (K) at position 650 (N650K, p.Asn650Lys). 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 medium size and polar (N) to large size and basic (K) 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 NDHMSD; likely pathogenic; changed glutamate-gated calcium ion channel activity; mutant channels are activated at 8-fold lower glutamate concentrations and 5-fold lower glycine concentrations; reduced localization to cell membrane. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 650 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 938 The length of the canonical sequence.
Location on the sequence: help RILGMVWAGFAMIIVASYTA N LAAFLVLDRPEERITGINDP 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                         RILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGINDP

                              RILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGINDP

Mouse                         RILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGINDP

Rat                           RILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGINDP

Xenopus laevis                RILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGINDP
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 19 – 938 Glutamate receptor ionotropic, NMDA 1
Topological domain 649 – 811 Extracellular
Mutagenesis 642 – 642 I -> L. Slight decrease in glutamate and glycine agonist potency; mutant channels are activated at 2-fold higher glutamate and glycine concentrations.
Mutagenesis 644 – 644 V -> M. Increase in glutamate and glycine agonist potency; mutant channels are activated lower glutamate and glycine concentrations.
Mutagenesis 653 – 653 A -> G. Increase in glutamate and glycine agonist potency; mutant channels are activated lower glutamate and glycine concentrations.
Helix 627 – 654



Literature citations
GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders.
Ohba C.; Shiina M.; Tohyama J.; Haginoya K.; Lerman-Sagie T.; Okamoto N.; Blumkin L.; Lev D.; Mukaida S.; Nozaki F.; Uematsu M.; Onuma A.; Kodera H.; Nakashima M.; Tsurusaki Y.; Miyake N.; Tanaka F.; Kato M.; Ogata K.; Saitsu H.; Matsumoto N.;
Epilepsia 56:841-848(2015)
Cited for: VARIANTS NDHMSD GLU-552; ILE-641; LYS-650 AND ARG-815; 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 NDHMSD SER-637; VAL-637; ALA-638; VAL-638; ILE-641; LEU-641; VAL-641; THR-642; VAL-643; CYS-647; SER-647; ILE-650; LYS-650; THR-652; THR-653; CYS-654 AND GLN-655; CHARACTERIZATION OF VARIANTS NDHMSD VAL-637; VAL-638; ILE-641; THR-642; CYS-647; SER-647; ILE-650; LYS-650; THR-653; CYS-654 AND GLN-655; MUTAGENESIS OF ILE-642; VAL-644 AND ALA-653; FUNCTION; SUBCELLULAR LOCATION;
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.