UniProtKB/Swiss-Prot P24752: Variant p.Ala301Pro

Acetyl-CoA acetyltransferase, mitochondrial
Gene: ACAT1
Chromosomal location: 11q22.3-q23.1
Variant information

Variant position:  301
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Alanine (A) to Proline (P) at position 301 (A301P, p.Ala301Pro).
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 small size and hydrophobic (A) to medium size and hydrophobic (P)
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 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. 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; 5% normal activity.
Any additional useful information about the variant.



Sequence information

Variant position:  301
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:   ANASTLNDGAAALVLMTADA  A KRLNVTPLARIVAFADAAVE
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                         ANASTLNDGAAALVLMTADAAKRLNVTPLARIVAFADAAVE

Mouse                         ANASTLNDGAAALVLMTAEAAQRLNVKPLARIAAFADAAVD

Rat                           ANASTLNDGAAAVVLMTAEAAQRLKVKPLARIAAFADAAVD

Bovine                        ANASTLNDGAAAVVLMTADAAKRLNVKPLARIAAFADAAVE

Xenopus tropicalis            ANASTLNDGAAALVLMTAGAASRLNVTPLARIVAFADAAVD

Zebrafish                     ANASTLNDGAAALVLMTADAAQRLNVTPLAKIVAFADAAVA

Baker's yeast                 ANASPINDGAAAVILVSEKVLKEKNLKPLAIIKGWGEAAHQ

Fission yeast                 ANASTLNDGASALVLMSAAKVKELGLKPLAKIIGWGEAAQD

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.

TypePositionsDescription
Chain 34 – 427 Acetyl-CoA acetyltransferase, mitochondrial
Metal binding 281 – 281 Potassium; via carbonyl oxygen
Metal binding 283 – 283 Potassium; via carbonyl oxygen
Binding site 284 – 284 Coenzyme A
Helix 298 – 303


Literature citations

Molecular, biochemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients.
Wakazono A.; Fukao T.; Yamaguchi S.; Hori T.; Orii T.; Lambert M.; Mitchell G.A.; Lee G.W.; Hashimoto T.;
Hum. Mutat. 5:34-42(1995)
Cited for: VARIANTS 3KTD ASP-158; MET-297 AND PRO-301;

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.