UniProtKB/SwissProt variant VAR

Variant information

Variant position:

557

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Proline (P) to Arginine (R) at position 557 (P557R, p.Pro557Arg).

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 medium size and hydrophobic (P) to large size and basic (R)

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

Involvement in disease:

Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (NDHMSD) [MIM:614254]: An autosomal dominant neurodevelopmental disorder characterized by severe mental retardation and developmental delay, absent speech, muscular hypotonia, dyskinesia, and hyperkinetic movements. Cortical blindness, cerebral atrophy, and seizures are present in some patients. {ECO:0000269|PubMed:21376300, ECO:0000269|PubMed:25167861, ECO:0000269|PubMed:25864721, ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28228639, ECO:0000269|PubMed:28389307}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In NDHMSD; changed localization to the cell membrane; loss of glutamate-gated calcium ion channel activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs878853143 [ dbSNP | Ensembl ]

Sequence information

Variant position:

557

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:

GLTILVKKEIPRSTLDSFMQ P FQSTLWLLVGLSVHVVAVML

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                         GLTILVKKEIPRSTLDSFMQPFQSTLWLLVGLSVHVVAVML

                              GLTILVKKEIPRSTLDSFMQPFQSTLWLLVGLSVHVVAVML

Mouse                         GLTILVKKEIPRSTLDSFMQPFQSTLWLLVGLSVHVVAVML

Rat                           GLTILVKKEIPRSTLDSFMQPFQSTLWLLVGLSVHVVAVML

Xenopus laevis                GLTILVKKEIPRSTLDSFMQPFQSTLWLLVGLSVHVVAVML

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
Topological domain	19 – 559	Extracellular

Literature citations

Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.
Redin C.; Gerard B.; Lauer J.; Herenger Y.; Muller J.; Quartier A.; Masurel-Paulet A.; Willems M.; Lesca G.; El-Chehadeh S.; Le Gras S.; Vicaire S.; Philipps M.; Dumas M.; Geoffroy V.; Feger C.; Haumesser N.; Alembik Y.; Barth M.; Bonneau D.; Colin E.; Dollfus H.; Doray B.; Delrue M.A.; Drouin-Garraud V.; Flori E.; Fradin M.; Francannet C.; Goldenberg A.; Lumbroso S.; Mathieu-Dramard M.; Martin-Coignard D.; Lacombe D.; Morin G.; Polge A.; Sukno S.; Thauvin-Robinet C.; Thevenon J.; Doco-Fenzy M.; Genevieve D.; Sarda P.; Edery P.; Isidor B.; Jost B.; Olivier-Faivre L.; Mandel J.L.; Piton A.;
J. Med. Genet. 51:724-736(2014)
Cited for: VARIANT NDHMSD ARG-557;

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; VARIANTS NDHMSR TRP-217 AND 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 VARIANTS NDHMSR TRP-217 AND 556-GLN--SER-938 DEL;

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 VARIANT NDHMSD GLU-552 AND ARG-557;

UniProtKB/Swiss-Prot Q05586: Variant p.Pro557Arg