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UniProtKB/Swiss-Prot Q13224: Variant p.Asn615Ile

Glutamate receptor ionotropic, NMDA 2B
Gene: GRIN2B
Variant information

Variant position:  615
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 Asparagine (N) to Isoleucine (I) at position 615 (N615I, p.Asn615Ile).
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 polar (N) to medium size and hydrophobic (I)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 DEE27; severe phenotype with early onset seizures; gain of function mutation; results in neuronal hyperexcitability; the mutant channel is not inhibited by magnesium and has increased calcium permeability compared to wild-type.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  615
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1484
The length of the canonical sequence.

Location on the sequence:   PGGPSFTIGKAIWLLWGLVF  N NSVPVQNPKGTTSKIMVSVW
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                         PGGPSFTIGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVW

                              PGGPSFTIGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVW

Mouse                         PGGPSFTIGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVW

Rat                           PGGPSFTIGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVW

Xenopus laevis                PGGPSFTIGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVW

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.

TypePositionsDescription
Chain 27 – 1484 Glutamate receptor ionotropic, NMDA 2B
Intramembrane 604 – 623 Discontinuously helical
Region 604 – 623 Pore-forming
Site 615 – 615 Functional determinant of NMDA receptors


Literature citations

GRIN2B mutations in West syndrome and intellectual disability with focal epilepsy.
Lemke J.R.; Hendrickx R.; Geider K.; Laube B.; Schwake M.; Harvey R.J.; James V.M.; Pepler A.; Steiner I.; Hortnagel K.; Neidhardt J.; Ruf S.; Wolff M.; Bartholdi D.; Caraballo R.; Platzer K.; Suls A.; De Jonghe P.; Biskup S.; Weckhuysen S.;
Ann. Neurol. 75:147-154(2014)
Cited for: INVOLVEMENT IN DEE27; VARIANTS DEE27 HIS-540; ILE-615 AND GLY-618; CHARACTERIZATION OF VARIANTS DEE27 HIS-540; ILE-615 AND GLY-618;

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.