UniProtKB/Swiss-Prot P50213: Variant p.Met204Ile

Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial
Gene: IDH3A
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Variant information Variant position:

204 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Methionine (M) to Isoleucine (I) at position 204 (M204I, p.Met204Ile). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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
Variant description:

In RP90; uncertain significance. Any additional useful information about the variant.

Sequence information Variant position:

204 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

366 The length of the canonical sequence.
Location on the sequence:

FEYARNNHRSNVTAVHKANI M RMSDGLFLQKCREVAESCKD 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                         FEYARNNHRSNVTAVHKANIMRMSDGLFLQKCREVAESCKD

Mouse                         FEYARNNHRSNVTAVHKANIMRMSDGLFLQKCREVAENCKD

Rat                           FEYARNNHRSNVTAVHKANIMRMSDGLFLQKCREVAENCKD

Pig                           FEYARNNHRSNVTAVHKANIMRMSDGLFLQKCREVAENCKD

Bovine                        FEYARNNHRSNVTAVHKANIMRMSDGLFLQKCREVAENCKD

Caenorhabditis elegans        FEYARQNGRKVVTAVHKANIMRQSDGLFLSICREQAALYPD

Drosophila                    FQYAKNNNRKKVTVVHKANIMRMSDGLFLRCVRDMAQKFPE

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 – 366	Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial
Site	200 – 200	Critical for catalysis
Modified residue	223 – 223	N6-acetyllysine
Mutagenesis	200 – 200	K -> A. Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate.
Mutagenesis	202 – 202	N -> A. Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate.
Mutagenesis	208 – 208	D -> A. Complete loss of the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP.

Literature citations
A novel variant in IDH3A identified in a case with Leber congenital amaurosis accompanied by macular pseudocoloboma.
Sun W.; Zhang Q.;
Ophthalmic Genet. 39:662-663(2018)
Cited for: VARIANT RP90 ILE-204; INVOLVEMENT IN RP90;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.