UniProtKB/SwissProt variant VAR

Variant information

Variant position:

319

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 Glycine (G) to Arginine (R) at position 319 (G319R, p.Gly319Arg).

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 glycine (G) to large size and basic (R)

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

Involvement in disease:

3-methylcrotonoyl-CoA carboxylase 2 deficiency (MCC2D) [MIM:210210]: An autosomal recessive disorder of leucine catabolism. The phenotype is variable, ranging from neonatal onset with severe neurological involvement to asymptomatic adults. There is a characteristic organic aciduria with massive excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, usually in combination with a severe secondary carnitine deficiency. {ECO:0000269|PubMed:11170888, ECO:0000269|PubMed:11181649, ECO:0000269|PubMed:11406611, ECO:0000269|PubMed:16010683, ECO:0000269|PubMed:17968484, ECO:0000269|PubMed:21071250, ECO:0000269|PubMed:22150417, ECO:0000269|PubMed:22264772, ECO:0000269|PubMed:22642865, ECO:0000269|PubMed:25382614, ECO:0000269|PubMed:27601257}. 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 MCC2D.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1443551700 [ dbSNP | Ensembl ]

Sequence information

Variant position:

319

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

Protein sequence length:

563

The length of the canonical sequence.

Location on the sequence:

KLDVTIEPSEEPLFPADELY G IVGANLKRSFDVREVIARIV

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                         KLDVTIEPS--EEPLFPADELYGIVGANLKRSFDVREVIARIV

Mouse                         KMDVTIEPS--EEPLFPADELYGIVGANLKRSFDVREVIAR

Rat                           KLDVTVEPS--EEPLFPADELYGIVGANLKRSFDVREVIAR

Caenorhabditis elegans        EEHMTFNPNA-DEPLYPAEEIYGIVGSNLKKTYDVREVIAR

Drosophila                    NFQTATPPSAVEEPRYDAEELYGIVGPNLTKSFDVREVIAR

Slime mold                    QPSPVITET--EEPLYPTSELAGIVPSDLKKNFDIRKVIAR

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 – 563	Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial
Domain	309 – 555	CoA carboxyltransferase C-terminal
Region	49 – 555	Carboxyltransferase

Literature citations

Identification of eight novel mutations and transcript analysis of two splicing mutations in Chinese newborns with MCC deficiency.
Yang L.; Yang J.; Zhang T.; Weng C.; Hong F.; Tong F.; Yang R.; Yin X.; Yu P.; Huang X.; Qi M.;
Clin. Genet. 88:484-488(2015)
Cited for: VARIANTS MCC2D ILE-139 AND ARG-319;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9HCC0: Variant p.Gly319Arg