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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P19525: Variant p.Gly130Arg

Interferon-induced, double-stranded RNA-activated protein kinase
Gene: EIF2AK2
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Variant information Variant position: help 130 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 Glycine (G) to Arginine (R) at position 130 (G130R, p.Gly130Arg). 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 glycine (G) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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 DYT33; gain-of-function variant resulting in increased levels of phosphorylated EIF2AK2 and EIF2A in patient cells compared to controls. Any additional useful information about the variant.


Sequence information Variant position: help 130 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 551 The length of the canonical sequence.
Location on the sequence: help QKKRLTVNYEQCASGVHGPE G FHYKCKMGQKEYSIGTGSTK 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                         QKKRLTVNYEQCASGVHGPEGFHYKCKMGQKEYSIGTGSTK

Mouse                         QKKKLSVNYEQCEPNSELPQRFICKCKIGQTMYGTGSGVTK

Rat                           QKENLPVNFELCDPDSQLPHRFICKCKIGQTTYGTGFGANK

Fission yeast                 S------NYQDA------LHHLILQAR--------------
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 2 – 551 Interferon-induced, double-stranded RNA-activated protein kinase
Domain 100 – 167 DRBM 2
Region 2 – 180 (Microbial infection) Interaction with HCV NS5A
Beta strand 125 – 138



Literature citations
EIF2AK2 Missense Variants Associated with Early Onset Generalized Dystonia.
Kuipers D.J.S.; Mandemakers W.; Lu C.S.; Olgiati S.; Breedveld G.J.; Fevga C.; Tadic V.; Carecchio M.; Osterman B.; Sagi-Dain L.; Wu-Chou Y.H.; Chen C.C.; Chang H.C.; Wu S.L.; Yeh T.H.; Weng Y.H.; Elia A.E.; Panteghini C.; Marotta N.; Pauly M.G.; Kuehn A.A.; Volkmann J.; Lace B.; Meijer I.A.; Kandaswamy K.; Quadri M.; Garavaglia B.; Lohmann K.; Bauer P.; Mencacci N.E.; Lubbe S.J.; Klein C.; Bertoli-Avella A.M.; Bonifati V.;
Ann. Neurol. 89:485-497(2021)
Cited for: VARIANTS DYT33 THR-32; ARG-130 AND ALA-138; CHARACTERIZATION OF VARIANTS DYT33 THR-32 AND ARG-130; INVOLVEMENT IN DYT33; A Recurrent EIF2AK2 Missense Variant Causes Autosomal-Dominant Isolated Dystonia.
Musacchio T.; Zech M.; Reich M.M.; Winkelmann J.; Volkmann J.;
Ann. Neurol. 89:1257-1258(2021)
Cited for: VARIANT DYT33 ARG-130; INVOLVEMENT IN DYT33; Heterozygous EIF2AK2 Variant Causes Adolescence-Onset Generalized Dystonia Partially Responsive to DBS.
Magrinelli F.; Moualek D.; Tazir M.; Pacha L.A.; Verghese A.; Bhatia K.P.; Maroofian R.; Houlden H.;
Mov. Disord. Clin. Pract. 9:268-271(2022)
Cited for: VARIANT DYT33 ARG-130;
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.