UniProtKB/SwissProt variant VAR

Variant information

Variant position:

247

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 Lysine (K) to Glutamate (E) at position 247 (K247E, p.Lys247Glu).

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 basic (K) to medium size and acidic (E)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

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

Involvement in disease:

Acyl-CoA dehydrogenase very long-chain deficiency (ACADVLD) [MIM:201475]: An inborn error of mitochondrial fatty acid beta-oxidation which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form characterized by early onset, high mortality and high incidence of cardiomyopathy; a milder childhood form with later onset, characterized by hypoketotic hypoglycemia, low mortality and rare cardiomyopathy; an adult form, with isolated skeletal muscle involvement, rhabdomyolysis and myoglobinuria, usually triggered by exercise or fasting. {ECO:0000269|PubMed:10077518, ECO:0000269|PubMed:8554073, ECO:0000269|PubMed:9546340}. 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 ACADVLD.

Any additional useful information about the variant.

Sequence information

Variant position:

247

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

Protein sequence length:

655

The length of the canonical sequence.

Location on the sequence:

SIRTSAVPSPCGKYYTLNGS K LWISNGGLADIFTVFAKTPV

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                         SIRTSAVPSPCGKYYTLNGSKLWISNGGLADIFTVFAKTPV

Mouse                         SIRSSAIPSPCGKYYTLNGSKIWISNGGLADIFTVFAKTPI

Rat                           SIRSSAVPSPCGKYYTLNGSKIWISNGGLADIFTVFAKTPI

Bovine                        SIRSSAVPSPCGKYYTLNGSKIWISNGGLADIFTVFAKTPV

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	41 – 655	Very long-chain specific acyl-CoA dehydrogenase, mitochondrial
Region	41 – 482	Catalytic
Modified residue	237 – 237	S-nitrosocysteine
Modified residue	239 – 239	N6-acetyllysine; alternate
Modified residue	239 – 239	N6-succinyllysine; alternate
Beta strand	238 – 251

Literature citations

Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death.
Mathur A.; Sims H.F.; Gopalakrishnan D.; Gibson B.; Rinaldo P.; Vockley J.; Hug G.; Strauss A.W.;
Circulation 99:1337-1343(1999)
Cited for: VARIANTS ACADVLD GLU-130 DEL; PRO-213; GLU-247; MET-260; LYS-278 DEL; ALA-283; ASP-441; LEU-458; PRO-490; LYS-534; TRP-613 AND GLN-615;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49748: Variant p.Lys247Glu