UniProtKB/Swiss-Prot P12694: Variant p.Tyr438Asn

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

438 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 Tyrosine (Y) to Asparagine (N) at position 438 (Y438N, p.Tyr438Asn). 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
Variant description:

In MSUD1A; decreased solubility; loss of 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 rs137852870 [ dbSNP | Ensembl ]

Sequence information Variant position:

438 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:

AQLRKQQESLARHLQTYGEH Y PLDHFDK 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                         AQLRKQQESLARHLQTYGEHYP-LDHFDK-------

Chimpanzee                    AQLRKQQESLARHLQTYGEHYP-LDHFD

Mouse                         AQLRRQQESLARHLQTYGEHYP-LDHFE

Bovine                        AQLRKQQESLARHLQTYGEHYP-LDHFE

Caenorhabditis elegans        LRLRRQRDELDAHVAEYKEHYPMLETLQ

Slime mold                    PNLIEQQKELIEHLKLYPDEYP-LNQFA

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

Literature citations
Structure of the gene encoding the entire mature E1 alpha subunit of human branched-chain alpha-keto acid dehydrogenase complex.
Dariush N.; Fisher C.W.; Cox R.P.; Chuang D.T.;
FEBS Lett. 284:34-38(1991)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3-445; VARIANT MSUD1A ASN-438; 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; Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease.
Zhang B.; Edenberg H.J.; Crabb D.W.; Harris R.A.;
J. Clin. Invest. 83:1425-1429(1989)
Cited for: VARIANT MSUD1A ASN-438; A T-to-A substitution in the E1 alpha subunit gene of the branched-chain alpha-ketoacid dehydrogenase complex in two cell lines derived from Menonite maple syrup urine disease patients.
Matsuda I.; Nobukuni Y.; Mitsubuchi H.; Indo Y.; Endo F.; Asaka J.; Harada A.;
Biochem. Biophys. Res. Commun. 172:646-651(1990)
Cited for: VARIANT MSUD1A ASN-438; Occurrence of a Tyr393-->Asn (Y393N) mutation in the E1 alpha gene of the branched-chain alpha-keto acid dehydrogenase complex in maple syrup urine disease patients from a Mennonite population.
Fisher C.R.; Fisher C.W.; Chuang D.T.; Cox R.P.;
Am. J. Hum. Genet. 49:429-434(1991)
Cited for: VARIANT MSUD1A ASN-438; Maple syrup urine disease in Mennonites. Evidence that the Y393N mutation in E1 alpha impedes assembly of the E1 component of branched-chain alpha-keto acid dehydrogenase complex.
Fisher C.R.; Chuang J.L.; Cox R.P.; Fisher C.W.; Star R.A.; Chuang D.T.;
J. Clin. Invest. 88:1034-1037(1991)
Cited for: VARIANT MSUD1A ASN-438; 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.