Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13002: Variant p.Ala657Thr

Glutamate receptor ionotropic, kainate 2
Gene: GRIK2
Feedback?
Variant information Variant position: help 657 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 Alanine (A) to Threonine (T) at position 657 (A657T, p.Ala657Thr). 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 small size and hydrophobic (A) to medium size and polar (T) 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 NEDLAS; gain of function; when incorporated into kainate receptor, produces constitutively active channels with significantly altered gating kinetics; may decrease cell surface expression. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 657 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 908 The length of the canonical sequence.
Location on the sequence: help GGIWWFFTLIIISSYTANLA A FLTVERMESPIDSADDLAKQ 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                         GGIWWFFTLIIISSYTANLAAFLTVERMESPIDSADDLAKQ

Mouse                         GGIWWFFTLIIISSYTANLAAFLTVERMESPIDSADDLAKQ

Rat                           GGIWWFFTLIIISSYTANLAAFLTVERMESPIDSADDLAKQ

Xenopus laevis                GGIWWFFTLIIISSYTANLAAFLTVERMESPIDSADDLAKQ

Zebrafish                     GGIWWFFTLIIISSYTANLAAFLTVERMESPIDSADDLAKQ
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 32 – 908 Glutamate receptor ionotropic, kainate 2
Topological domain 657 – 819 Extracellular
Alternative sequence 509 – 695 Missing. In isoform 6.
Alternative sequence 510 – 714 Missing. In isoform 7.
Alternative sequence 585 – 908 Missing. In isoform 3.



Literature citations
A gain-of-function mutation in the GRIK2 gene causes neurodevelopmental deficits.
Guzman Y.F.; Ramsey K.; Stolz J.R.; Craig D.W.; Huentelman M.J.; Narayanan V.; Swanson G.T.;
Neurol. Genet. 3:E129-E129(2017)
Cited for: INVOLVEMENT IN NEDLAS; VARIANT NEDLAS THR-657; VARIANT ILE-867; CHARACTERIZATION OF VARIANT NEDLAS THR-657; FUNCTION; Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders.
Stolz J.R.; Foote K.M.; Veenstra-Knol H.E.; Pfundt R.; Ten Broeke S.W.; de Leeuw N.; Roht L.; Pajusalu S.; Part R.; Rebane I.; Ounap K.; Stark Z.; Kirk E.P.; Lawson J.A.; Lunke S.; Christodoulou J.; Louie R.J.; Rogers R.C.; Davis J.M.; Innes A.M.; Wei X.C.; Keren B.; Mignot C.; Lebel R.R.; Sperber S.M.; Sakonju A.; Dosa N.; Barge-Schaapveld D.Q.C.M.; Peeters-Scholte C.M.P.C.D.; Ruivenkamp C.A.L.; van Bon B.W.; Kennedy J.; Low K.J.; Ellard S.; Pang L.; Junewick J.J.; Mark P.R.; Carvill G.L.; Swanson G.T.;
Am. J. Hum. Genet. 108:1692-1709(2021)
Cited for: INVOLVEMENT IN NEDLAS; VARIANTS NEDLAS THR-657; ARG-660; LYS-660 AND THR-668; CHARACTERIZATION OF VARIANTS NEDLAS THR-657; ARG-660; LYS-660 AND THR-668; SUBCELLULAR LOCATION; 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.