UniProtKB/SwissProt variant VAR

Variant information

Variant position:

302

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 Arginine (R) to Glutamine (Q) at position 302 (R302Q, p.Arg302Gln).

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 medium size and polar (Q)

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:

Isobutyryl-CoA dehydrogenase deficiency (IBDD) [MIM:611283]: An autosomal recessive metabolic disorder characterized by plasma carnitine deficiency and elevated C4-acylcarnitine. Patients manifest variable clinical features including failure to thrive, seizures, anemia, muscular hypotonia and developmental delay. Some patients may be asymptomatic. {ECO:0000269|PubMed:12359132, ECO:0000269|PubMed:15505379, ECO:0000269|PubMed:16857760}. 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 IBDD; no effect on localization to the mitochondrion; complete loss of isobutyryl-CoA dehydrogenase activity; loss of protein expression in patient cells.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121908422 [ dbSNP | Ensembl ]

Sequence information

Variant position:

302

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

Protein sequence length:

415

The length of the canonical sequence.

Location on the sequence:

SCSLGAAHASVILTRDHLNV R KQFGEPLASNQYLQFTLADM

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                         SCSLGAAHASVILTRDHLNVRKQFGEPLASNQYLQFTLADM

Mouse                         SCSLGAAHASVILTQEHLKVRKQFGAPLARSQYLQFQLADM

Bovine                        SCSLGAAHASIVLARDYLKVRKQFGEPLANSQYLQFQLADM

Slime mold                    ACSLGGAQSCLVAARDHVKVRKQFNQPLEHFQAVQFKMADM

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	23 – 415	Isobutyryl-CoA dehydrogenase, mitochondrial
Binding site	302 – 302	FAD; shared with dimeric partner

Literature citations

Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans.
Nguyen T.V.; Andresen B.S.; Corydon T.J.; Ghisla S.; Abd El-Razik N.; Mohsen A.W.; Cederbaum S.D.; Roe D.S.; Roe C.R.; Lench N.J.; Vockley J.;
Mol. Genet. Metab. 77:68-79(2002)
Cited for: VARIANT IBDD GLN-302; CHARACTERIZATION OF VARIANT IBDD GLN-302; INVOLVEMENT IN IBDD; FUNCTION; CATALYTIC ACTIVITY; PATHWAY; BIOPHYSICOCHEMICAL PROPERTIES; SUBSTRATE SPECIFICITY; SUBCELLULAR LOCATION;

Variations in IBD (ACAD8) in children with elevated C4-carnitine detected by tandem mass spectrometry newborn screening.
Pedersen C.B.; Bischoff C.; Christensen E.; Simonsen H.; Lund A.M.; Young S.P.; Koeberl D.D.; Millington D.S.; Roe C.R.; Roe D.S.; Wanders R.J.A.; Ruiter J.P.N.; Keppen L.D.; Stein Q.; Knudsen I.; Gregersen N.; Andresen B.S.;
Pediatr. Res. 60:315-320(2006)
Cited for: VARIANTS IBDD TYR-134; ARG-137; THR-152; GLN-302; THR-320; CYS-334 AND ARG-385; CHARACTERIZATION OF VARIANTS IBDD ARG-137; GLN-302 AND THR-320; FUNCTION; CATALYTIC ACTIVITY; PATHWAY;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9UKU7: Variant p.Arg302Gln