UniProtKB/Swiss-Prot P12694: Variant p.Tyr413Cys

2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial
Gene: BCKDHA
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Variant information Variant position:

413 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Tyrosine (Y) to Cysteine (C) at position 413 (Y413C, p.Tyr413Cys). 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 (C) 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 MSUD1A; uncertain significance; decreased solubility; changed mitochondrial alpha-ketoglutarate dehydrogenase complex assembly; loss of 3-methyl-2-oxobutanoate dehydrogenase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs398123508 [ dbSNP | Ensembl ]

Sequence information Variant position:

413 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

445 The length of the canonical sequence.
Location on the sequence:

AFEQAERKPKPNPNLLFSDV Y QEMPAQLRKQQESLARHLQT 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                         AFEQAERKPKPNPNLLFSDVYQEMPAQLRKQQESLARHLQT

Chimpanzee                    AFEQAERKPKPNPNLLFSDVYQEMPAQLRKQQESLARHLQT

Mouse                         AFEQAERKLKPNPSLLFSDVYQEMPAQLRRQQESLARHLQT

Bovine                        AFEQAERKLKPNPSLIFSDVYQEMPAQLRKQQESLARHLQT

Caenorhabditis elegans        EFAAAEKRKKAHYHDLFEDVYDELPLRLRRQRDELDAHVAE

Slime mold                    SLVNAEKQYKPSINEIFTDVYDKPTPNLIEQQKELIEHLKL

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	46 – 445	2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial
Beta strand	412 – 415

Literature citations
Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease.
Aevarsson A.; Chuang J.L.; Wynn R.M.; Turley S.; Chuang D.T.; Hol W.G.J.;
Structure 8:277-291(2000)
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 46-445 IN COMPLEX WITH BCKDHB; THIAMINE PYROPHOSPHATE; POTASSIUM AND MAGNESIUM; FUNCTION; CATALYTIC ACTIVITY; COFACTOR; SUBUNIT; SUBCELLULAR LOCATION; VARIANTS MSUD1A ASP-254 AND HIS-297; CHARACTERIZATION OF VARIANTS MSUD1A SER-159; LYS-190; MET-211; SER-249; THR-253; ASP-254; TRP-265; SER-267; PRO-285; ARG-290; HIS-297; ARG-310; CYS-409; CYS-413 AND ASN-438; Molecular basis of maple syrup urine disease: novel mutations at the E1 alpha locus that impair E1(alpha 2 beta 2) assembly or decrease steady-state E1 alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex.
Chuang J.L.; Fisher C.R.; Cox R.P.; Chuang D.T.;
Am. J. Hum. Genet. 55:297-304(1994)
Cited for: VARIANT MSUD1A CYS-413; Impaired assembly of E1 decarboxylase of the branched-chain alpha-ketoacid dehydrogenase complex in type IA maple syrup urine disease.
Wynn R.M.; Davie J.R.; Chuang J.L.; Cote C.D.; Chuang D.T.;
J. Biol. Chem. 273:13110-13118(1998)
Cited for: VARIANTS MSUD1A SER-249; TRP-265; SER-267; PRO-285; ARG-290; ARG-310; CYS-409; CYS-413 AND ASN-438; CHARACTERIZATION OF VARIANTS MSUD1A SER-249; TRP-265; SER-267; PRO-285; ARG-290; ARG-310; CYS-409; CYS-413 AND ASN-438; FUNCTION; CATALYTIC ACTIVITY; SUBUNIT;

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.