UniProtKB/SwissProt variant VAR

Variant information

Variant position:

469

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 Arginine (R) to Tryptophan (W) at position 469 (R469W, p.Arg469Trp).

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 (R) to large size and aromatic (W)

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

BLOSUM score:

-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:

In ACADVLD; decreased protein abundance; loss of fatty acid beta-oxidation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs113994170 [ dbSNP | Ensembl ]

Sequence information

Variant position:

469

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:

ERVLRDLRIFRIFEGTNDIL R LFVALQGCMDKGKELSGLGS

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                         ERVLRDLRIFRIFEGTNDILRLFVALQGCMDKGKELSGLGS

Mouse                         ERVLRDIRIFRIFEGANDILRLFVALQGCMDKGKELTGLGN

Rat                           ERVLRDIRIFRIFEGTNDILRLFVALQGCMDKGKELTGLGN

Bovine                        ERVLRDLRIFRIFEGTNDILRLFVALQGCMDKGKELSGLGN

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
Active site	462 – 462	Proton acceptor
Modified residue	482 – 482	N6-acetyllysine; alternate
Modified residue	482 – 482	N6-succinyllysine; alternate
Mutagenesis	458 – 458	F -> T. Decreased acyl-CoA dehydrogenase activity. Decreased affinity for acyl-CoA. No effect on FAD cofactor-binding.
Mutagenesis	458 – 458	F -> V. Loss of acyl-CoA dehydrogenase activity. Loss of FAD cofactor-binding.
Mutagenesis	458 – 458	F -> Y. Decreased acyl-CoA dehydrogenase activity. No effect on affinity for acyl-CoA. Decreased FAD cofactor-binding.
Mutagenesis	462 – 462	E -> D. Decreased acyl-CoA dehydrogenase activity. No effect on affinity for acyl-CoA. No effect on FAD cofactor-binding.
Mutagenesis	462 – 462	E -> Q. Loss of acyl-CoA dehydrogenase activity. No effect on FAD cofactor-binding.
Helix	465 – 485

Literature citations

Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.
Andresen B.S.; Olpin S.; Poorthuis B.J.H.M.; Scholte H.R.; Vianey-Saban C.; Wanders R.; Ijlst L.; Morris A.; Pourfarzam M.; Bartlett K.; Baumgartner E.R.; de Klerk J.B.C.; Schroeder L.D.; Corydon T.J.; Lund H.; Winter V.; Bross P.; Bolund L.; Gregersen N.;
Am. J. Hum. Genet. 64:479-494(1999)
Cited for: VARIANTS ACADVLD MET-260; ALA-283; TRP-469; PRO-502 AND TRP-613;

Expression and characterization of mutations in human very long-chain acyl-CoA dehydrogenase using a prokaryotic system.
Goetzman E.S.; Wang Y.; He M.; Mohsen A.W.; Ninness B.K.; Vockley J.;
Mol. Genet. Metab. 91:138-147(2007)
Cited for: CATALYTIC ACTIVITY (ISOFORM 2); SUBCELLULAR LOCATION (ISOFORM 2); TOPOLOGY (ISOFORM 2); CHARACTERIZATION OF VARIANT ACADVLD MET-260; ALA-283; TRP-469; PRO-490; PRO-502 AND TRP-613;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49748: Variant p.Arg469Trp