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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P08559: Variant p.Val167Met

Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Gene: PDHA1
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Variant information Variant position: help 167 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 Valine (V) to Methionine (M) at position 167 (V167M, p.Val167Met). 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 Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 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 PDHAD; disrupts magnesium binding and results in deficient activity of the pyruvate dehydrogenase complex. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 167 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 390 The length of the canonical sequence.
Location on the sequence: help KGKGGSMHMYAKNFYGGNGI V GAQVPLGAGIALACKYNGKD 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                         KGKGGSMHMYAKNFYGGNGIVGAQVPLGAGIALACKYNGKD

Chimpanzee                    KGKGGSMHMYAKNFYGGNGIVGAQVPLGAGIALACKYNGKD

Mouse                         KGKGGSMHMYAKNFYGGNGIVGAQVPLGAGIALACKYNGKD

Rat                           KGKGGSMHMYAKNFYGGNGIVGAQVPLGAGIALACKYNGKD

Bovine                        KGKGGSMHMYAKNFYGGNGIVGAQVPLGAGIALACKYNGKD

Caenorhabditis elegans        HGKGGSMHMYTKNFYGGNGIVGAQQPLGAGVALAMKYREQK

Slime mold                    KGKGGSMHMFTKNFYGGNGIVGAQCPLGAGIAFAQKYNKTG

Baker's yeast                 YGKGGSMHLYAPGFYGGNGIVGAQVPLGAGLAFAHQYKNED

Fission yeast                 KGKGGSMHIFAKNFYGGNGIVGAQIPLGAGIGFAQKYLEKP
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 30 – 390 Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Binding site 157 – 157
Binding site 165 – 165
Binding site 165 – 165
Binding site 167 – 167
Binding site 167 – 167
Turn 167 – 169



Literature citations
Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the alphaV138M variant of human pyruvate dehydrogenase.
Whitley M.J.; Arjunan P.; Nemeria N.S.; Korotchkina L.G.; Park Y.H.; Patel M.S.; Jordan F.; Furey W.;
J. Biol. Chem. 293:13204-13213(2018)
Cited for: X-RAY CRYSTALLOGRAPHY (2.69 ANGSTROMS) OF 30-390 OF VARIANT PDHAD MET-167 IN COMPLEX WITH MG(2+) AND THIAMINE DIPHOSPHATE AND OF WILD-TYPE IN COMPLEX WITH MG(2+) AND SUBSTRATE ANALOG; SUBUNIT; CHARACTERIZATION OF VARIANT PDHAD MET-167; Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase leading to deficiency of the pyruvate dehydrogenase complex.
Chun K.; McKay N.; Petrova-Benedict R.; Robinson B.H.;
Hum. Mol. Genet. 2:449-454(1993)
Cited for: VARIANTS PDHAD MET-167; THR-199; ALA-231; GLY-263 AND LEU-292;
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.