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UniProtKB/Swiss-Prot P08559: Variant p.Tyr243Asn

Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Gene: PDHA1
Variant information

Variant position:  243
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Tyrosine (Y) to Asparagine (N) at position 243 (Y243N, p.Tyr243Asn).
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 large size and aromatic (Y) to medium size and polar (N)
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

Involvement in disease:  Pyruvate dehydrogenase E1-alpha deficiency (PDHAD) [MIM:312170]: An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis. {ECO:0000269|PubMed:1293379, ECO:0000269|PubMed:1338114, ECO:0000269|PubMed:1551669, ECO:0000269|PubMed:1909401, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:7545958, ECO:0000269|PubMed:7573035, ECO:0000269|PubMed:7757088, ECO:0000269|PubMed:7887409, ECO:0000269|PubMed:7967473, ECO:0000269|PubMed:8032855, ECO:0000269|PubMed:8199595, ECO:0000269|PubMed:8498846, ECO:0000269|PubMed:8504306, ECO:0000269|PubMed:8664900, ECO:0000269|PubMed:8844217, ECO:0000269|PubMed:9266390, ECO:0000269|PubMed:9671272}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PDHAD.
Any additional useful information about the variant.

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



Sequence information

Variant position:  243
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  390
The length of the canonical sequence.

Location on the sequence:   ENNRYGMGTSVERAAASTDY  Y KRGDFIPGLRVDGMDILCVR
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                         ENNRYGMGTSVERAAASTDYYKRGDFIPGLRVDGMDILCVR

Chimpanzee                    ENNRYGMGTSVERAAASTDYYKRGDFIPGLRVDGMDILCVR

Mouse                         ENNRYGMGTSVERAAASTDYYKRGDFIPGLRVDGMDILCVR

Rat                           ENNRYGMGTSVERAAASTDYYKRGDFIPGLRVDGMDILCVR

Bovine                        ENNRYGMGTSVERAAASTDYYKRGDFIPGLRVDGMDILCVR

Caenorhabditis elegans        ENNGFGMGTTAERSSASTEYYTRGDYVPGIWVDGMDILAVR

Slime mold                    ENNKYGMGTSQKRSTAGHDFYTRGHYVAGLKVDGMDVFAVK

Baker's yeast                 ENNKYGMGTAASRSSAMTEYFKRGQYIPGLKVNGMDILAVY

Fission yeast                 ENNKYGMGTSAERSSAMTEFYKRGQYIPGLLVNGMDVLAVL

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 31 – 390 Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Modified residue 232 – 232 Phosphoserine; by PDK1
Modified residue 244 – 244 N6-acetyllysine; alternate
Modified residue 244 – 244 N6-succinyllysine; alternate
Mutagenesis 232 – 232 S -> A. Abolishes inactivation by phosphorylation; when associated with A-293 and A-300.
Helix 242 – 244


Literature citations

Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients.
Matthews P.M.; Brown R.M.; Otero L.J.; Marchington D.R.; LeGris M.; Howes R.; Meadows L.S.; Shevell M.; Scriver C.R.; Brown G.K.;
Brain 117:435-443(1994)
Cited for: VARIANTS PDHAD ASN-243; ASN-315 AND HIS-378; VARIANT LEU-282;

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.