UniProtKB/SwissProt variant VAR

Variant information

Variant position:

592

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

Type of variant:

Unclassified

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 Methionine (M) to Leucine (L) at position 592 (M592L, p.Met592Leu).

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:

Similar physico-chemical property. Both residues are medium size and hydrophobic.

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:

Found in a patient with autism spectrum disorder; unknown pathological significance.

Any additional useful information about the variant.

Sequence information

Variant position:

592

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

Protein sequence length:

1336

The length of the canonical sequence.

Location on the sequence:

VSPSAFLEPYSPAVWVMMFV M CLTVVAVTVFIFEYLSPVGY

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                         VSPSAFLEPYSPAVWVMMFVMCLTVVAVTVFIFEYLSPVGY

Mouse                         VSPSAFLEPYSPAVWVMMFVMCLTVVAVTVFIFEYLSPVGY

Rat                           VSPSAFLEPYSPAVWVMMFVMCLTVVAVTVFIFEYLSPVGY

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	28 – 1336	Glutamate receptor ionotropic, NMDA 2D
Transmembrane	585 – 603	Helical
Mutagenesis	580 – 580	P -> R. Changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency.

Literature citations

Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia.
Tarabeux J.; Kebir O.; Gauthier J.; Hamdan F.F.; Xiong L.; Piton A.; Spiegelman D.; Henrion E.; Millet B.; Fathalli F.; Joober R.; Rapoport J.L.; DeLisi L.E.; Fombonne E.; Mottron L.; Forget-Dubois N.; Boivin M.; Michaud J.L.; Drapeau P.; Lafreniere R.G.; Rouleau G.A.; Krebs M.O.;
Transl. Psychiatry 1:E55-E55(2011)
Cited for: VARIANTS VAL-466; LEU-592; VAL-733; HIS-872; ILE-883; VAL-922; THR-926; PRO-982 AND SER-1317;

UniProtKB/Swiss-Prot O15399: Variant p.Met592Leu