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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P08559: Variant p.Arg302Cys

Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Gene: PDHA1
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Variant information Variant position: help 302 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 Arginine (R) to Cysteine (C) at position 302 (R302C, p.Arg302Cys). 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 large size and basic (R) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 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; loss of activity; common mutation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 302 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 MELQTYRYHGHSMSDPGVSY R TREEIQEVRSKSDPIMLLKD 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                         MELQTYRYHGHSMSDPGVSYRTREEIQEVRSKSDPIMLLKD

Chimpanzee                    MELQTYRYHGHSMSGPGVSYRTREEIQEVRSKSDPIMLLKD

Mouse                         MELQTYRYHGHSMSDPGVSYRTREEIQEVRSKSDPIMLLKD

Rat                           MELQTYRYHGHSMSDPGVSYRTREEIQEVRSKSDPIMLLKD

Bovine                        MELQTYRYHGHSMSDPGVSYRTREEIQEVRSKSDPIMLLKD

Caenorhabditis elegans        MEMATYRYHGHSMSDPGTSYRTREEIQEVRKTRDPITGFKD

Slime mold                    LEMDTYRYVGHSMSDPGITYRTREEVNHVRQTRDPIENIRQ

Baker's yeast                 LEYETYRYGGHSMSDPGTTYRTRDEIQHMRSKNDPIAGLKM

Fission yeast                 MEFVTYRYGGHSMSDPGTTYRSREEVQKVRAARDPIEGLKK
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 292 – 292
Modified residue 293 – 293 Phosphoserine; by PDK1, PDK2, PDK3 and PDK4
Modified residue 295 – 295 Phosphoserine
Modified residue 300 – 300 Phosphoserine; by PDK1, PDK2, PDK3 and PDK4
Modified residue 301 – 301 Phosphotyrosine
Modified residue 313 – 313 N6-acetyllysine; alternate
Modified residue 313 – 313 N6-succinyllysine; alternate
Modified residue 321 – 321 N6-acetyllysine
Mutagenesis 293 – 293 S -> A. Reduces enzyme activity. Abolishes inactivation by phosphorylation; when associated with A-232 and A-300.
Mutagenesis 293 – 293 S -> E. Interferes with substrate binding.
Mutagenesis 300 – 300 S -> A. Abolishes inactivation by phosphorylation; when associated with A-232 and A-293.
Beta strand 300 – 302



Literature citations
X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation.
Dahl H.-H.M.; Hansen L.L.; Brown R.M.; Danks D.M.; Rogers J.G.; Brown G.K.;
J. Inherit. Metab. Dis. 15:835-847(1992)
Cited for: VARIANT PDHAD CYS-302; Mutation analysis of the pyruvate dehydrogenase E1 alpha gene in eight patients with a pyruvate dehydrogenase complex deficiency.
Lissens W.; de Meirleir L.; Seneca S.; Benelli C.; Marsac C.; Poll-The B.T.; Briones P.; Ruitenbeek W.; van Diggelen O.; Chaigne D.; Ramaekers V.; Liebaers I.;
Hum. Mutat. 7:46-51(1996)
Cited for: VARIANTS PDHAD CYS-72; ASP-113; ARG-162; GLY-263; HIS-288 AND CYS-302; Arginine 302 mutations in the pyruvate dehydrogenase E1alpha subunit gene: identification of further patients and in vitro demonstration of pathogenicity.
Otero L.J.; Brown R.M.; Brown G.K.;
Hum. Mutat. 12:114-121(1998)
Cited for: VARIANTS PDHAD CYS-302 AND HIS-302; Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes.
Parrini E.; Marini C.; Mei D.; Galuppi A.; Cellini E.; Pucatti D.; Chiti L.; Rutigliano D.; Bianchini C.; Virdo S.; De Vita D.; Bigoni S.; Barba C.; Mari F.; Montomoli M.; Pisano T.; Rosati A.; Guerrini R.;
Hum. Mutat. 38:216-225(2017)
Cited for: VARIANT PDHAD CYS-302;
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.