UniProtKB/Swiss-Prot P05067: Variant p.Leu705Val

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

Variant position:  705
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 Leucine (L) to Valine (V) at position 705 (L705V, p.Leu705Val).
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

Involvement in disease:  Cerebral amyloid angiopathy, APP-related (CAA-APP) [MIM:605714]: A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications. 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 CAA-APP; Italian type.
Any additional useful information about the variant.



Sequence information

Variant position:  705
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:   HQKLVFFAEDVGSNKGAIIG  L MVGGVVIATVIVITLVMLKK
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.

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 672 – 711 Beta-amyloid protein 40
Chain 688 – 770 C83
Peptide 688 – 713 P3(42)
Peptide 688 – 711 P3(40)
Chain 691 – 770 C80
Transmembrane 700 – 723 Helical
Metal binding 685 – 685 Copper or zinc 2
Site 704 – 704 Implicated in free radical propagation
Site 706 – 706 Susceptible to oxidation
Glycosylation 697 – 697 O-linked (GalNAc...)
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.
Beta strand 702 – 705


Literature citations

A novel AbetaPP mutation exclusively associated with cerebral amyloid angiopathy.
Obici L.; Demarchi A.; de Rosa G.; Bellotti V.; Marciano S.; Donadei S.; Arbustini E.; Palladini G.; Diegoli M.; Genovese E.; Ferrari G.; Coverlizza S.; Merlini G.;
Ann. Neurol. 58:639-644(2005)
Cited for: VARIANT CAA-APP VAL-705;

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.