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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99986: Variant p.Gly135Arg

Serine/threonine-protein kinase VRK1
Gene: VRK1
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Variant information Variant position: help 135 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 135 (G135R, p.Gly135Arg). 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 HMNR10; likely pathogenic; severely reduced kinase activity resulting in severely decreased autophosphorylation and phosphorylation of COIL, H3, H2AX, TP53, JUN and TP53BP1; reduced protein stability; the orthologous mouse mutation results in defective Cajal bodies assembly; loss of function in DNA damage response. Any additional useful information about the variant.


Sequence information Variant position: help 135 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 396 The length of the canonical sequence.
Location on the sequence: help GSGLHDKNGKSYRFMIMDRF G SDLQKIYEANAKRFSRKTVL 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                         GSGLHDKNGKSYRFMIMDRFGSDLQKIYEANAKRFSRKTVL

Mouse                         GSGLHDKNGKSYRFMIMDRFGSDLQKIYEANAKRFSRKTVL

Bovine                        GSGLHDKNGKSYRFMIIDRFGSDLQKIYEANAKRFSRKTVL

Zebrafish                     GSGFHEKNGKRYRFMVMDRFGTDLQKLFEGNGKKFSRKLVL

Caenorhabditis elegans        ANGYFTYESEKMRYMIIPKYATSLEAVRETNGGTLAMKDSL
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 1 – 396 Serine/threonine-protein kinase VRK1
Domain 37 – 317 Protein kinase
Mutagenesis 125 – 125 S -> A. Does not abolish autophosphorylation.
Mutagenesis 150 – 150 S -> A. Does not abolish autophosphorylation.
Beta strand 134 – 137



Literature citations
Novel motor phenotypes in patients with VRK1 mutations without pontocerebellar hypoplasia.
Stoll M.; Teoh H.; Lee J.; Reddel S.; Zhu Y.; Buckley M.; Sampaio H.; Roscioli T.; Farrar M.; Nicholson G.;
Neurology 87:65-70(2016)
Cited for: VARIANTS HMNR10 ARG-119; ARG-135; VAL-195 AND 358-ARG--LYS-396 DEL; INVOLVEMENT IN HMNR10;
VRK1 functional insufficiency due to alterations in protein stability or kinase activity of human VRK1 pathogenic variants implicated in neuromotor syndromes.
Martin-Doncel E.; Rojas A.M.; Cantarero L.; Lazo P.A.;
Sci. Rep. 9:13381-13381(2019)
Cited for: CHARACTERIZATION OF VARIANTS HMNR10 GLN-89; ARG-119; ARG-135; VAL-195; MET-236 AND CYS-321; CHARACTERIZATION OF VARIANTS PCH1A CYS-133 AND 358-ARG--LYS-396 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.