UniProtKB/SwissProt variant VAR

Variant information

Variant position:

20

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 Histidine (H) to Proline (P) at position 20 (H20P, p.His20Pro).

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 medium size and polar (H) to medium size and hydrophobic (P)

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 MEVA.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104895295 [ dbSNP | Ensembl ]

Sequence information

Variant position:

20

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:

MLSEVLLVSAPGKVILHGE H AVVHGKVALAVSLNLRTFLR

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                         MLSEVLLVSAPGKVILHGEHAVVHGKVALAVSLN-LRTFLR

Mouse                         MLSEALLVSAPGKVILHGEHAVVHGKVALAAALN-LRTFL

Rat                           MLSEVLLVSAPGKVILHGEHAVVHGKVALAVALN-LRTFL

Bovine                        MLSEVLLVSAPGKVILHGEHAVVHGKVALAVALN-LRTFL

Slime mold                    NQDNIIQVSAPGKIILFGEHAVVLEKTAIASALS-LRTTV

Baker's yeast                 -MSLPFLTSAPGKVIIFGEHSAVYNKPAVAASVSALRTYL

Fission yeast                 -MSKSLIVSSPGKTILFGEHAVVYGATALAAAVS-LRSYC

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.

Type	Positions	Description
Chain	1 – 396	Mevalonate kinase
Binding site	13 – 13	ATP
Mutagenesis	19 – 19	E -> D. No change in protein stability. Weak decrease in kinase activity. Approximately 2-fold decrease in Vmax. Approximately 2-fold decrease affinity for ATP and mevalonate.
Turn	19 – 21

Literature citations

Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome.
Houten S.M.; Koster J.; Romeijn G.-J.; Frenkel J.; Di Rocco M.; Caruso U.; Landrieu P.; Kelley R.I.; Kuis W.; Poll-The B.T.; Gibson K.M.; Wanders R.J.A.; Waterham H.R.;
Eur. J. Hum. Genet. 9:253-259(2001)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS HIDS PRO-20; PRO-39; LEU-135; THR-148; THR-268 AND ILE-377; VARIANTS MEVA PRO-20; PHE-264; THR-268; MET-310 AND THR-334;

Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome.
Houten S.M.; Kuis W.; Duran M.; de Koning T.J.; van Royen-Kerkhof A.; Romeijn G.J.; Frenkel J.; Dorland L.; de Barse M.M.J.; Huijbers W.A.R.; Rijkers G.T.; Waterham H.R.; Wanders R.J.A.; Poll-The B.T.;
Nat. Genet. 22:175-177(1999)
Cited for: VARIANTS HIDS PRO-20; THR-268 AND ILE-377;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q03426: Variant p.His20Pro