UniProtKB/Swiss-Prot Q05586: Variant p.Tyr647Ser

Glutamate receptor ionotropic, NMDA 1
Gene: GRIN1
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Variant information Variant position:

647 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 Tyrosine (Y) to Serine (S) at position 647 (Y647S, p.Tyr647Ser). 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 aromatic (Y) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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 NDHMSD; likely pathogenic; decreased ion transmembrane transport; reduced localization to cell membrane; changed glutamate-gated calcium ion channel activity; mutant channels are activated at 50-fold lower glutamate concentrations and 28-fold lower glycine concentrations. Any additional useful information about the variant.

Sequence information Variant position:

647 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

938 The length of the canonical sequence.
Location on the sequence:

FSARILGMVWAGFAMIIVAS Y TANLAAFLVLDRPEERITGI 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                         FSARILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGI

                              FSARILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGI

Mouse                         FSARILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGI

Rat                           FSARILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGI

Xenopus laevis                FSARILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGI

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.

Type	Positions	Description
Chain	19 – 938	Glutamate receptor ionotropic, NMDA 1
Transmembrane	631 – 647	Helical
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
Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy.
Lemke J.R.; Geider K.; Helbig K.L.; Heyne H.O.; Schuetz H.; Hentschel J.; Courage C.; Depienne C.; Nava C.; Heron D.; Moeller R.S.; Hjalgrim H.; Lal D.; Neubauer B.A.; Nuernberg P.; Thiele H.; Kurlemann G.; Arnold G.L.; Bhambhani V.; Bartholdi D.; Pedurupillay C.R.; Misceo D.; Frengen E.; Stroemme P.; Dlugos D.J.; Doherty E.S.; Bijlsma E.K.; Ruivenkamp C.A.; Hoffer M.J.; Goldstein A.; Rajan D.S.; Narayanan V.; Ramsey K.; Belnap N.; Schrauwen I.; Richholt R.; Koeleman B.P.; Sa J.; Mendonca C.; de Kovel C.G.; Weckhuysen S.; Hardies K.; De Jonghe P.; De Meirleir L.; Milh M.; Badens C.; Lebrun M.; Busa T.; Francannet C.; Piton A.; Riesch E.; Biskup S.; Vogt H.; Dorn T.; Helbig I.; Michaud J.L.; Laube B.; Syrbe S.;
Neurology 86:2171-2178(2016)
Cited for: VARIANTS NDHMSD GLU-552; ARG-557; ARG-618; ARG-620; SER-645; SER-647; ARG-815; VAL-815; LEU-817; ARG-827 AND CYS-844; VARIANT NDHMSR TRP-217; VARIANT DEE101 556-GLN--SER-938 DEL; CHARACTERIZATION OF VARIANTS NDHMSD ARG-557; ARG-618; ARG-620; SER-645; SER-647; ARG-815; LEU-817; ARG-827 AND CYS-844; CHARACTERIZATION OF VARIANT NDHMSR TRP-217; CHARACTERIZATION OF VARIANT DEE101 556-GLN--SER-938 DEL; 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;

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.