UniProtKB/Swiss-Prot Q12879: Variant p.Ile605Met

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

605 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Isoleucine (I) to Methionine (M) at position 605 (I605M, p.Ile605Met). 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:

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:

Found in schizophrenia; uncertain significance; unchanged function in ion transmembrane transport; unchanged agonist potency and channel activation by glutamate. Any additional useful information about the variant.

Sequence information Variant position:

605 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:

NRNLAKGKAPHGPSFTIGKA I WLLWGLVFNNSVPVQNPKGT 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                         NRNLAKGKAPHGPSFTIGKAIWLLWGLVFNNSVPVQNPKGT

Chimpanzee                    NRNLAKGKAPHGPSFTIGKAIWLLWGLVFNNSVPVQNPKGT

Mouse                         NRNLAKGKAPHGPSFTIGKAIWLLWGLVFNNSVPVQNPKGT

Rat                           NRNLAKGKAPHGPSFTIGKAIWLLWGLVFNNSVPVQNPKGT

Xenopus laevis                NRNLAQGKDPHGPSFTIGKAVWLLWGLVFNNSVPVQNPKGT

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
Intramembrane	601 – 615	Discontinuously helical
Region	599 – 620	Pore-forming
Site	614 – 614	Functional determinant of NMDA receptors
Helix	600 – 613

Literature citations
Rare coding variants in ten genes confer substantial risk for schizophrenia.
Singh T.; Poterba T.; Curtis D.; Akil H.; Al Eissa M.; Barchas J.D.; Bass N.; Bigdeli T.B.; Breen G.; Bromet E.J.; Buckley P.F.; Bunney W.E.; Bybjerg-Grauholm J.; Byerley W.F.; Chapman S.B.; Chen W.J.; Churchhouse C.; Craddock N.; Cusick C.M.; DeLisi L.; Dodge S.; Escamilla M.A.; Eskelinen S.; Fanous A.H.; Faraone S.V.; Fiorentino A.; Francioli L.; Gabriel S.B.; Gage D.; Gagliano Taliun S.A.; Ganna A.; Genovese G.; Glahn D.C.; Grove J.; Hall M.H.; Haemaelaeinen E.; Heyne H.O.; Holi M.; Hougaard D.M.; Howrigan D.P.; Huang H.; Hwu H.G.; Kahn R.S.; Kang H.M.; Karczewski K.J.; Kirov G.; Knowles J.A.; Lee F.S.; Lehrer D.S.; Lescai F.; Malaspina D.; Marder S.R.; McCarroll S.A.; McIntosh A.M.; Medeiros H.; Milani L.; Morley C.P.; Morris D.W.; Mortensen P.B.; Myers R.M.; Nordentoft M.; O'Brien N.L.; Olivares A.M.; Ongur D.; Ouwehand W.H.; Palmer D.S.; Paunio T.; Quested D.; Rapaport M.H.; Rees E.; Rollins B.; Satterstrom F.K.; Schatzberg A.; Scolnick E.; Scott L.J.; Sharp S.I.; Sklar P.; Smoller J.W.; Sobell J.L.; Solomonson M.; Stahl E.A.; Stevens C.R.; Suvisaari J.; Tiao G.; Watson S.J.; Watts N.A.; Blackwood D.H.; Boerglum A.D.; Cohen B.M.; Corvin A.P.; Esko T.; Freimer N.B.; Glatt S.J.; Hultman C.M.; McQuillin A.; Palotie A.; Pato C.N.; Pato M.T.; Pulver A.E.; St Clair D.; Tsuang M.T.; Vawter M.P.; Walters J.T.; Werge T.M.; Ophoff R.A.; Sullivan P.F.; Owen M.J.; Boehnke M.; O'Donovan M.C.; Neale B.M.; Daly M.J.;
Nature 604:509-516(2022)
Cited for: VARIANTS 58-GLU--VAL-1464 DEL; ARG-591; MET-605; CYS-698; 700-TYR--VAL-1464 DEL; ALA-784; ILE-788; MET-794; PRO-811 AND THR-1295; INVOLVEMENT IN SCHIZOPHRENIA; Differential functional consequences of GRIN2A mutations associated with schizophrenia and neurodevelopmental disorders.
Shepard N.; Baez-Nieto D.; Iqbal S.; Kurganov E.; Budnik N.; Campbell A.J.; Pan J.Q.; Sheng M.; Farsi Z.;
Sci. Rep. 14:2798-2798(2024)
Cited for: CHARACTERIZATION OF VARIANTS 58-GLU--GLU-1461 DEL; LEU-576; LYS-586; ARG-591; MET-605; ILE-653; HIS-671; CYS-698; 700-TYR--VAL-1464 DEL; ARG-707; VAL-727; THR-727; MET-775; ALA-784; ILE-788; MET-794; ARG-809; PRO-811; MET-812; LEU-967; THR-1295 AND 1339-LYS--VAL-1464 DEL; FUNCTION;

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.