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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P42261: Variant p.Ala636Thr

Glutamate receptor 1
Gene: GRIA1
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Variant information Variant position: help 636 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 636 (A636T, p.Ala636Thr). 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 MRD67; increased AMPA glutamate receptor activity; increased sensitivity towards glutamate; no effect on localization to the cell membrane. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 636 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 906 The length of the canonical sequence.
Location on the sequence: help GGVWWFFTLIIISSYTANLA A FLTVERMVSPIESAEDLAKQ 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                         GGVWWFFTLIIISSYTANLAAFLTVERMVSPIESAEDLAKQ

Mouse                         GGVWWFFTLIIISSYTANLAAFLTVERMVSPIESAEDLAKQ

Rat                           GGVWWFFTLIIISSYTANLAAFLTVERMVSPIESAEDLAKQ

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 19 – 906 Glutamate receptor 1
Topological domain 631 – 805 Extracellular
Modified residue 645 – 645 Phosphoserine



Literature citations
Diagnostic exome sequencing in persons with severe intellectual disability.
de Ligt J.; Willemsen M.H.; van Bon B.W.; Kleefstra T.; Yntema H.G.; Kroes T.; Vulto-van Silfhout A.T.; Koolen D.A.; de Vries P.; Gilissen C.; del Rosario M.; Hoischen A.; Scheffer H.; de Vries B.B.; Brunner H.G.; Veltman J.A.; Vissers L.E.;
N. Engl. J. Med. 367:1921-1929(2012)
Cited for: VARIANT MRD67 THR-636; INVOLVEMENT IN MRD67; Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains.
Geisheker M.R.; Heymann G.; Wang T.; Coe B.P.; Turner T.N.; Stessman H.A.F.; Hoekzema K.; Kvarnung M.; Shaw M.; Friend K.; Liebelt J.; Barnett C.; Thompson E.M.; Haan E.; Guo H.; Anderlid B.M.; Nordgren A.; Lindstrand A.; Vandeweyer G.; Alberti A.; Avola E.; Vinci M.; Giusto S.; Pramparo T.; Pierce K.; Nalabolu S.; Michaelson J.J.; Sedlacek Z.; Santen G.W.E.; Peeters H.; Hakonarson H.; Courchesne E.; Romano C.; Kooy R.F.; Bernier R.A.; Nordenskjoeld M.; Gecz J.; Xia K.; Zweifel L.S.; Eichler E.E.;
Nat. Neurosci. 20:1043-1051(2017)
Cited for: VARIANT MRD67 THR-636; CHARACTERIZATION OF VARIANT MRD67 THR-636; INVOLVEMENT IN MRD67; FUNCTION; Identification and functional evaluation of GRIA1 missense and truncation variants in individuals with ID: An emerging neurodevelopmental syndrome.
Ismail V.; Zachariassen L.G.; Godwin A.; Sahakian M.; Ellard S.; Stals K.L.; Baple E.; Brown K.T.; Foulds N.; Wheway G.; Parker M.O.; Lyngby S.M.; Pedersen M.G.; Desir J.; Bayat A.; Musgaard M.; Guille M.; Kristensen A.S.; Baralle D.;
Am. J. Hum. Genet. 109:1217-1241(2022)
Cited for: VARIANTS MRD67 GLN-345; THR-627; THR-636 AND ASP-745; CHARACTERIZATION OF VARIANTS MRD67 GLN-345; THR-627; THR-636 AND ASP-745; VARIANT MRT76 377-ARG--LEU-906 DEL; CHARACTERIZATION OF VARIANT MRT76 377-ARG--LEU-906 DEL; INVOLVEMENT IN MRT76; 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.