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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13224: Variant p.Arg540His

Glutamate receptor ionotropic, NMDA 2B
Gene: GRIN2B
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Variant information Variant position: help 540 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 Arginine (R) to Histidine (H) at position 540 (R540H, p.Arg540His). 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 large size and basic (R) to medium size and polar (H) 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 DEE27; decreased protein abundance; decreased localization to the cell membrane; increased glutamate-gated calcium ion channel activity via an allosteric effect which is characterized by increased glutamate and glycine potency and increased open probability; the mutant channel is less sensitive to magnesium inhibition and has increased calcium permeability compared to wild-type. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 540 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1484 The length of the canonical sequence.
Location on the sequence: help SEVVDFSVPFIETGISVMVS R SNGTVSPSAFLEPFSADVWV 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                         SEVVDFSVPFIETGISVMVSRSNGTVSPSAFLEPFSADVWV

                              SEVVDFSVPFIETGISVMVSRSNGTVSPSAFLEPFSADVWV

Mouse                         SEVVDFSVPFIETGISVMVSRSNGTVSPSAFLEPFSADVWV

Rat                           SEVVDFSVPFIETGISVMVSRSNGTVSPSAFLEPFSADVWV

Xenopus laevis                SEVVDFSVPFIETGISVMVSRSNGTVSPSAFLEPFSADVWV
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 27 – 1484 Glutamate receptor ionotropic, NMDA 2B
Topological domain 27 – 555 Extracellular
Glycosylation 542 – 542 N-linked (GlcNAc...) asparagine
Mutagenesis 553 – 553 P -> R. Changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency and slowed response rise time and deactivation time course.



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; FUNCTION; TRANSPORTER ACTIVITY; Mechanistic insight into NMDA receptor dysregulation by rare variants in the GluN2A and GluN2B agonist binding domains.
Swanger S.A.; Chen W.; Wells G.; Burger P.B.; Tankovic A.; Bhattacharya S.; Strong K.L.; Hu C.; Kusumoto H.; Zhang J.; Adams D.R.; Millichap J.J.; Petrovski S.; Traynelis S.F.; Yuan H.;
Am. J. Hum. Genet. 99:1261-1280(2016)
Cited for: VARIANTS MRD6 ARG-436; PHE-461 AND HIS-696; CHARACTERIZATION OF VARIANTS MRD6 GLY-413; ARG-436; TYR-456; PHE-461; CYS-682 AND HIS-696; CHARACTERIZATION OF VARIANT DEE27 HIS-540; FUNCTION; TRANSPORTER ACTIVITY; 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.