UniProtKB/SwissProt variant VAR

Variant information

Variant position:

312

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 Isoleucine (I) to Threonine (T) at position 312 (I312T, p.Ile312Thr).

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 medium size and hydrophobic (I) to medium size and polar (T)

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:

3-ketothiolase deficiency (3KTD) [MIM:203750]: An autosomal recessive inborn error of isoleucine catabolism characterized by intermittent ketoacidotic attacks associated with unconsciousness. Some patients die during an attack or are mentally retarded. Urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, triglylglycine, butanone is increased. It seems likely that the severity of this disease correlates better with the environmental or acquired factors than with the ACAT1 genotype. {ECO:0000269|PubMed:1346617, ECO:0000269|PubMed:1715688, ECO:0000269|PubMed:7728148, ECO:0000269|PubMed:9744475}. 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 3KTD; decreased protein stability; decreased acetyl-CoA C-acyltransferase activity; less than 10% of the degradative/thiolase activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs120074146 [ dbSNP | Ensembl ]

Sequence information

Variant position:

312

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

Protein sequence length:

427

The length of the canonical sequence.

Location on the sequence:

ALVLMTADAAKRLNVTPLAR I VAFADAAVEPIDFPIAPVYA

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                         ALVLMTADAAKRLNVTPLARIVAFADAAVEPIDFPIAPVYA

Mouse                         ALVLMTAEAAQRLNVKPLARIAAFADAAVDPIDFPLAPAYA

Rat                           AVVLMTAEAAQRLKVKPLARIAAFADAAVDPIDFPLAPAYA

Bovine                        AVVLMTADAAKRLNVKPLARIAAFADAAVEPIDFPLAPAYA

Xenopus tropicalis            ALVLMTAGAASRLNVTPLARIVAFADAAVDPIDFPIAPAYA

Zebrafish                     ALVLMTADAAQRLNVTPLAKIVAFADAAVAPIDFPIAPAFA

Baker's yeast                 AVILVSEKVLKEKNLKPLAIIKGWGEAAHQPADFTWAPSLA

Fission yeast                 ALVLMSAAKVKELGLKPLAKIIGWGEAAQDPERFTTSPSLA

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	34 – 427	Acetyl-CoA acetyltransferase, mitochondrial
Alternative sequence	163 – 427	Missing. In isoform 2.
Beta strand	310 – 319

Literature citations

Characterization of N93S, I312T, and A333P missense mutations in two Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency.
Fukao T.; Nakamura H.; Song X.-Q.; Nakamura K.; Orii K.E.; Kohno Y.; Kano M.; Yamaguchi S.; Hashimoto T.; Orii T.; Kondo N.;
Hum. Mutat. 12:245-254(1998)
Cited for: VARIANTS 3KTD SER-93; THR-312 AND PRO-333; CHARACTERIZATION OF VARIANTS 3KTD SER-93; THR-312 AND PRO-333; FUNCTION; CATALYTIC ACTIVITY; PATHWAY;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P24752: Variant p.Ile312Thr