UniProtKB/SwissProt variant VAR

Variant information

Variant position:

259

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 Aspartate (D) at position 259 (G259D, p.Gly259Asp).

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 medium size and acidic (D)

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:

Infantile cerebellar-retinal degeneration (ICRD) [MIM:614559]: A severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration. {ECO:0000269|PubMed:22405087, ECO:0000269|PubMed:25351951}. 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 ICRD.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs786204828 [ dbSNP | Ensembl ]

Sequence information

Variant position:

259

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

Protein sequence length:

780

The length of the canonical sequence.

Location on the sequence:

SGWSSPKDVILKVAGILTVK G GTGAIVEYHGPGVDSISCTG

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                         SGWSSPKDVILKVAGILTVKGGTGAIVEYHGPGVDSISCTG

Mouse                         SGWTSPKDVILKVAGILTVKGGTGAIVEYHGPGVDSISCTG

Rat                           SGWTSPKDVILKVAGILTVKGGTGAIVEYHGPGVDSISCTG

Pig                           SGWTSPKDVILKVAGILTVKGGTGAIVEYHGPGVDSISCTG

Bovine                        SGWTSPKDVILKVAGILTVKGGTGAIVEYHGPGVDSISCTG

Caenorhabditis elegans        NGWTSAKDVILKVADILTVKGGTGAIVEYFGPGVDSISATG

Slime mold                    KGWSSPKDVILRVADILTVKGGTGAIVEYFGSGVESLSCTG

Baker's yeast                 NGWTSPKDIILKLAGITTVKGGTGKIVEYFGDGVDTFSATG

Fission yeast                 KGWTSPKDVILKVAGILTVKGGTGAIVEYFGPGVESLSCTG

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	28 – 780	Aconitate hydratase, mitochondrial

Literature citations

Mutations in the tricarboxylic acid cycle enzyme, aconitase 2, cause either isolated or syndromic optic neuropathy with encephalopathy and cerebellar atrophy.
Metodiev M.D.; Gerber S.; Hubert L.; Delahodde A.; Chretien D.; Gerard X.; Amati-Bonneau P.; Giacomotto M.C.; Boddaert N.; Kaminska A.; Desguerre I.; Amiel J.; Rio M.; Kaplan J.; Munnich A.; Rotig A.; Rozet J.M.; Besmond C.;
J. Med. Genet. 51:834-838(2014)
Cited for: INVOLVEMENT IN OPA9; INVOLVEMENT IN ICRD; VARIANTS OPA9 VAL-74 AND ARG-661; VARIANTS ICRD ASP-259 AND ASN-736;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99798: Variant p.Gly259Asp