UniProtKB/Swiss-Prot Q12879: Variant p.Asp731Asn

Glutamate receptor ionotropic, NMDA 2A
Gene: GRIN2A
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Variant information Variant position:

731 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 Aspartate (D) to Asparagine (N) at position 731 (D731N, p.Asp731Asn). 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 acidic (D) to medium size and polar (N) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 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 FESD; likely pathogenic; decreased protein abundance; decreased localization to the cell membrane; decreased glutamate-gated calcium ion channel activity characterized by drastically decreased glutamate agonist potency, decreased glycine agonist potency, reduced amplitude of current response, shortened synaptic-like response time course, decreased channel open probability and enhanced sensitivity to negative allosteric modulators. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs796052549 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

1464 The length of the canonical sequence.
Location on the sequence:

KGVEDALVSLKTGKLDAFIY D AAVLNYKAGRDEGCKLVTIG 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                         KGVEDALVSLKTGKLDAFIYDAAVLNYKAGRDEGCKLVTIG

Chimpanzee                    KGVEDALVSLKTGKLDAFIYDAAVLNYKAGRDEGCKLVTIG

Mouse                         RGVEDALVSLKTGKLDAFIYDAAVLNYKAGRDEGCKLVTIG

Rat                           RGVEDALVSLKTGKLDAFIYDAAVLNYKAGRDEGCKLVTIG

Xenopus laevis                KGVQDALVSLKTGKLDAFIYDAAVLNYMAGRDEGCKLVTIG

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	23 – 1464	Glutamate receptor ionotropic, NMDA 2A
Topological domain	646 – 816	Extracellular
Binding site	730 – 731
Beta strand	726 – 731

Literature citations
GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction.
Lesca G.; Rudolf G.; Bruneau N.; Lozovaya N.; Labalme A.; Boutry-Kryza N.; Salmi M.; Tsintsadze T.; Addis L.; Motte J.; Wright S.; Tsintsadze V.; Michel A.; Doummar D.; Lascelles K.; Strug L.; Waters P.; de Bellescize J.; Vrielynck P.; de Saint Martin A.; Ville D.; Ryvlin P.; Arzimanoglou A.; Hirsch E.; Vincent A.; Pal D.; Burnashev N.; Sanlaville D.; Szepetowski P.;
Nat. Genet. 45:1061-1066(2013)
Cited for: VARIANTS FESD SER-184; SER-295; ARG-483; TRP-504; HIS-518; THR-548; VAL-652; ASN-669; THR-694; THR-716; ASN-731; ASN-933 AND ASN-1251; VARIANT GLY-1276; CHARACTERIZATION OF VARIANTS FESD HIS-518 AND VAL-652; 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 FESD ALA-506 AND GLY-685; CHARACTERIZATION OF VARIANT FESD ARG-436; ARG-483; TRP-504; ALA-506; HIS-518; MET-531; ASN-669; GLY-685; THR-694; SER-699; VAL-705; LYS-714; THR-716; THR-727; ASN-731; LEU-734; GLU-772; CHARACTERIZATION OF VARIANT MET-452; A de novo loss-of-function GRIN2A mutation associated with childhood focal epilepsy and acquired epileptic aphasia.
Gao K.; Tankovic A.; Zhang Y.; Kusumoto H.; Zhang J.; Chen W.; XiangWei W.; Shaulsky G.H.; Hu C.; Traynelis S.F.; Yuan H.; Jiang Y.;
PLoS ONE 12:E0170818-E0170818(2017)
Cited for: VARIANT FESD ASN-731; CHARACTERIZATION OF VARIANT FESD ASN-731; Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency - molecular profiling and functional rescue.
Addis L.; Virdee J.K.; Vidler L.R.; Collier D.A.; Pal D.K.; Ursu D.;
Sci. Rep. 7:66-66(2017)
Cited for: CHARACTERIZATION OF VARIANTS ARG-79; TYR-231; ARG-436; ARG-483; VAL-705; LYS-714; ASN-731; THR-814; ASN-933 AND SER-976; SUBCELLULAR LOCATION; GRIN2A-related disorders: genotype and functional consequence predict phenotype.
Strehlow V.; Heyne H.O.; Vlaskamp D.R.M.; Marwick K.F.M.; Rudolf G.; de Bellescize J.; Biskup S.; Brilstra E.H.; Brouwer O.F.; Callenbach P.M.C.; Hentschel J.; Hirsch E.; Kind P.C.; Mignot C.; Platzer K.; Rump P.; Skehel P.A.; Wyllie D.J.A.; Hardingham G.E.; van Ravenswaaij-Arts C.M.A.; Lesca G.; Lemke J.R.;
Brain 142:80-92(2019)
Cited for: VARIANTS FESD GLN-411; SER-498; CYS-518; VAL-532; GLN-611; SER-614; THR-635; GLY-644; SER-648; VAL-649; PRO-649; ILE-653; THR-654; ALA-684; GLN-695; GLY-713; THR-716; ASN-731; THR-733; ARG-809; VAL-817 AND GLU-818;

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.