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UniProtKB/Swiss-Prot Q03426: Variant p.Ala148Thr

Mevalonate kinase
Gene: MVK
Variant information

Variant position:  148
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 Alanine (A) to Threonine (T) at position 148 (A148T, p.Ala148Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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.
Any additional useful information about the variant.

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



Sequence information

Variant position:  148
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:   SLDIVVWSELPPGAGLGSSA  A YSVCLAAALLTVCEEIPNPL
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                         SLDIVVWSELPPGAGLGSSAAYSVCLAAALL-----TVCEEIPNPL

Mouse                         SLDMVVWSELPPGAGLGSSAAYSVCLAAALL-----TACEE

Rat                           SLDIMVWSELPPGAGLGSSAAYSVCVAAALL-----TACEE

Bovine                        SLDITVWSELPTGAGLGSSAAYSVCLAAALL-----TACEE

Slime mold                    AYNIKITSDLPIGAGLGSSASFCVSICAGLLKAFDTYICGG

Baker's yeast                 NIKFSLKSTLPIGAGLGSSASISVSLALAMA-----YLGGL

Fission yeast                 GCTLTISSQVPLGAGLGSSATISVVVATSLL-----LAFGN

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 146 – 146 Proton donor
Metal binding 146 – 146 Magnesium
Binding site 135 – 135 ATP
Mutagenesis 145 – 145 S -> A. Modest changes in KM for ATP. 20-fold increase in KM for mevalonate. Approximately 2-fold decrease in Vmax.
Mutagenesis 146 – 146 S -> A. Modest changes in KM for ATP. 20-fold increase in KM for mevalonate. 4000-fold decrease in Vmax.
Mutagenesis 149 – 149 Y -> A. No effect on kinase activity. Approximately 4- and 8-fold decrease affinities for ATP and mevalonate, respectively.
Helix 145 – 160


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;

MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever.
D'Osualdo A.; Picco P.; Caroli F.; Gattorno M.; Giacchino R.; Fortini P.; Corona F.; Tommasini A.; Salvi G.; Specchia F.; Obici L.; Meini A.; Ricci A.; Seri M.; Ravazzolo R.; Martini A.; Ceccherini I.;
Eur. J. Hum. Genet. 13:314-320(2005)
Cited for: VARIANTS HIDS GLN-20; ILE-132; THR-148; ARG-171; GLU-211; GLN-215; ILE-250; ARG-265; THR-268; MET-310; VAL-376 AND ILE-377; VARIANTS ASN-52 AND MET-356;

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.