UniProtKB/Swiss-Prot P05067: Variant p.Ala713Val

Amyloid beta A4 protein
Gene: APP
Chromosomal location: 21q21.2
Variant information

Variant position:  713
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Alanine (A) to Valine (V) at position 713 (A713V, p.Ala713Val).
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 (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 one chronic schizophrenia patient; unknown pathological significance.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  713
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  770
The length of the canonical sequence.

Location on the sequence:   EDVGSNKGAIIGLMVGGVVI  A TVIVITLVMLKKKQYTSIHH
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                         EDVGSNKGAIIGLMVGGVVIATVI-VITLVMLKKKQYTSIH-H

Chimpanzee                    EDVGSNKGAIIGLMVGGVVIATVI-VITLVMLKKKQYTSIH

Mouse                         EDVGSNKGAIIGLMVGGVVIATVI-VITLVMLKKKQYTSIH

Rat                           EDVGSNKGAIIGLMVGGVVIATVI-VITLVMLKKKQYTSIH

Pig                           EDVGSNKGAIIGLMVGGVVIATVI-VITLVMLKKKQYTSIH

Caenorhabditis elegans        EVERSASSVFQPYVLASAMFITAICIIAFAITNARRRRAM-

Drosophila                    HAAKEGRNVYFTLSFAGIALMAAV-FVGVAVAKWRTSRSPH

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 18 – 770 Amyloid beta A4 protein
Chain 672 – 770 C99
Chain 672 – 713 Beta-amyloid protein 42
Chain 688 – 770 C83
Peptide 688 – 713 P3(42)
Chain 691 – 770 C80
Chain 712 – 770 Gamma-secretase C-terminal fragment 59
Transmembrane 700 – 723 Helical
Site 704 – 704 Implicated in free radical propagation
Site 706 – 706 Susceptible to oxidation
Site 713 – 714 Cleavage; by gamma-secretase; site 2
Modified residue 729 – 729 Phosphothreonine
Modified residue 730 – 730 Phosphoserine; by APP-kinase I
Alternative sequence 306 – 770 Missing. In isoform APP305.
Mutagenesis 704 – 704 G -> V. Reduced protein oxidation. No hippocampal neuron toxicity.
Mutagenesis 706 – 706 M -> L. Reduced lipid peroxidation inhibition.
Mutagenesis 706 – 706 M -> V. No free radical production. No hippocampal neuron toxicity.
Mutagenesis 717 – 717 V -> CS. Unchanged beta-APP42/total APP-beta ratio.
Mutagenesis 717 – 717 V -> FGI. Increased beta-APP42/beta-APP40 ratio.
Mutagenesis 717 – 717 V -> K. Decreased beta-APP42/total APP-beta ratio.
Mutagenesis 717 – 717 V -> M. Increased beta-APP42/beta-APP40 ratio. No change in apoptosis after caspase cleavage.
Mutagenesis 728 – 728 Y -> A. No effect on APBA1 nor APBB1 binding. Greatly reduces the binding to APPBP2. APP internalization unchanged. No change in beta-APP42 secretion.


Literature citations

Mutation in codon 713 of the beta amyloid precursor protein gene presenting with schizophrenia.
Jones C.T.; Morris S.; Yates C.M.; Moffoot A.; Sharpe C.; Brock D.J.H.; St Clair D.;
Nat. Genet. 1:306-309(1992)
Cited for: VARIANT VAL-713;

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.