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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q14831: Variant p.Thr675Lys

Metabotropic glutamate receptor 7
Gene: GRM7
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Variant information Variant position: help 675 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Threonine (T) to Lysine (K) at position 675 (T675K, p.Thr675Lys). 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 medium size and polar (T) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In NEDSHBA; uncertain significance. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 675 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 915 The length of the canonical sequence.
Location on the sequence: help CSFRRVFLGLGMCISYAALL T KTNRIYRIFEQGKKSVTAPR 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                         CSFRRVFLGLGMCISYAALLTKTNRIYRIFEQGKKSVTAPR

Mouse                         CSFRRVFLGLGMCISYAALLTKTNRIYRIFEQGKKSVTAPR

Rat                           CSFRRVFLGLGMCISYAALLTKTNRIYRIFEQGKKSVTAPR

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 35 – 915 Metabotropic glutamate receptor 7
Transmembrane 655 – 675 Helical; Name=3
Mutagenesis 658 – 658 R -> W. Does not rescue axon outgrowth defects when expressed in an heterologous system; when associated with K-675. Decreased protein abundance due to increased proteasomal degradation; when associated with K-675. Loss of localization to the cell membrane; when associated with K-675.
Mutagenesis 675 – 675 T -> K. Does not rescue axon outgrowth defects when expressed in an heterologous system; when associated with W-658. Decreased protein abundance due to increased proteasomal degradation; when associated with W-658. Loss of localization to the cell membrane; when associated with W-658.



Literature citations
Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate.
Charng W.L.; Karaca E.; Coban Akdemir Z.; Gambin T.; Atik M.M.; Gu S.; Posey J.E.; Jhangiani S.N.; Muzny D.M.; Doddapaneni H.; Hu J.; Boerwinkle E.; Gibbs R.A.; Rosenfeld J.A.; Cui H.; Xia F.; Manickam K.; Yang Y.; Faqeih E.A.; Al Asmari A.; Saleh M.A.; El-Hattab A.W.; Lupski J.R.;
BMC Med. Genomics 9:42-42(2016)
Cited for: INVOLVEMENT IN NEDSHBA; VARIANTS NEDSHBA THR-154; TRP-658 AND LYS-675; Biallelic GRM7 variants cause epilepsy, microcephaly, and cerebral atrophy.
Marafi D.; Mitani T.; Isikay S.; Hertecant J.; Almannai M.; Manickam K.; Abou Jamra R.; El-Hattab A.W.; Rajah J.; Fatih J.M.; Du H.; Karaca E.; Bayram Y.; Punetha J.; Rosenfeld J.A.; Jhangiani S.N.; Boerwinkle E.; Akdemir Z.C.; Erdin S.; Hunter J.V.; Gibbs R.A.; Pehlivan D.; Posey J.E.; Lupski J.R.;
Ann. Clin. Transl. Neurol. 7:610-627(2020)
Cited for: VARIANTS NEDSHBA THR-154; 586-TRP--ILE-915 DEL; GLN-658; TRP-658; 659-ARG--ILE-915 DEL; LYS-675 AND LYS-891;
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.