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UniProtKB/Swiss-Prot Q03426: Variant p.Gly202Arg

Mevalonate kinase
Gene: MVK
Variant information

Variant position:  202
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Glycine (G) to Arginine (R) at position 202 (G202R, p.Gly202Arg).
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:  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:  -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:  In HIDS and POROK3.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  202
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  396
The length of the canonical sequence.

Location on the sequence:   LELINKWAFQGERMIHGNPS  G VDNAVSTWGGALRYHQGKIS
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         LELINKWAFQGERMIHGNPSGVDNAVSTWGGALRYHQ----GKIS

Mouse                         LKSINKWAFEGERVIHGNPSGVDNAVSTWGGALRFQQ----

Rat                           LKSINKWAYEGERVIHGNPSGVDNSVSTWGGALRYQQ----

Bovine                        LELINKWAFQGERVIHGNPSGVDNAVSTWGGALRYQQ----

Slime mold                    LNLINLWSLQGEKIMHGTPSGIDNAVATFGKALTFTR----

Baker's yeast                 KHIVNQWAFIGEKCIHGTPSGIDNAVATYGNALLFEKDSHN

Fission yeast                 LALIEAWSFLGECCIHGTPSGIDNAVATNGGLIAFRK----

Sequence annotation in neighborhood:  
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 Mevalonate kinase
Active site 204 – 204 Proton acceptor
Metal binding 193 – 193 Magnesium
Mutagenesis 193 – 193 E -> Q. No change in protein stability. Decreased kinase activity. Approximately 50-fold decrease in Vmax. Approximately 20- and 40-fold decrease affinities for ATP and mevalonate, respectively.
Mutagenesis 196 – 196 I -> A. No effect on kinase activity. Approximately 2- and 3-fold decrease affinities for ATP and mevalonate, respectively.
Mutagenesis 201 – 201 S -> A. Modest changes in KM for ATP. 100-fold increase in KM for mevalonate. Approximately 2-fold increase in Vmax.
Mutagenesis 204 – 204 D -> A. No change in protein stability. Loss of kinase activity. Normal affinities for ATP and mevalonate.
Mutagenesis 204 – 204 D -> N. No change in protein stability. Loss of kinase activity. Normal affinities for ATP and mevalonate.


Literature citations

Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis.
Zhang S.Q.; Jiang T.; Li M.; Zhang X.; Ren Y.Q.; Wei S.C.; Sun L.D.; Cheng H.; Li Y.; Yin X.Y.; Hu Z.M.; Wang Z.Y.; Liu Y.; Guo B.R.; Tang H.Y.; Tang X.F.; Ding Y.T.; Wang J.B.; Li P.; Wu B.Y.; Wang W.; Yuan X.F.; Hou J.S.; Ha W.W.; Wang W.J.; Zhai Y.J.; Wang J.; Qian F.F.; Zhou F.S.; Chen G.; Zuo X.B.; Zheng X.D.; Sheng Y.J.; Gao J.P.; Liang B.; Li P.; Zhu J.; Xiao F.L.; Wang P.G.; Cui Y.; Li H.; Liu S.X.; Gao M.; Fan X.; Shen S.K.; Zeng M.; Sun G.Q.; Xu Y.; Hu J.C.; He T.T.; Li Y.R.; Yang H.M.; Wang J.; Yu Z.Y.; Zhang H.F.; Hu X.; Yang K.; Wang J.; Zhao S.X.; Zhou Y.W.; Liu J.J.; Du W.D.; Zhang L.; Xia K.; Yang S.; Wang J.; Zhang X.J.;
Nat. Genet. 44:1156-1160(2012)
Cited for: INVOLVEMENT IN POROK3; VARIANTS POROK3 ARG-12; PRO-41; ARG-202; PRO-255; PRO-279; ASP-291; ARG-312; SER-365 AND SER-376;

Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome.
Cuisset L.; Drenth J.P.H.; Simon A.; Vincent M.-F.; van der Velde-Visser S.D.; van der Meer J.W.M.; Grateau G.; Delpech M.;
Eur. J. Hum. Genet. 9:260-266(2001)
Cited for: VARIANTS HIDS ASN-20; PRO-20; PRO-39; LEU-150; LEU-167; ARG-202; GLN-215; THR-268; SER-309; ARG-326 AND ILE-377; VARIANT MEVA THR-334; VARIANT ASN-52;

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.