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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49768: Variant p.Leu219Pro

Presenilin-1
Gene: PSEN1
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Variant information Variant position: help 219 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Leucine (L) to Proline (P) at position 219 (L219P, p.Leu219Pro). 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: help 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: help -3 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: help In AD3. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 219 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 467 The length of the canonical sequence.
Location on the sequence: help ALLIWNFGVVGMISIHWKGP L RLQQAYLIMISALMALVFIK 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: help 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 1 – 298 Presenilin-1 NTF subunit
Topological domain 217 – 220 Cytoplasmic
Alternative sequence 185 – 467 Missing. In isoform 4.
Mutagenesis 202 – 202 I -> F. Nearly abolishes protease activity with APP.
Mutagenesis 212 – 212 S -> Y. Nearly abolishes protease activity with APP.
Mutagenesis 214 – 214 H -> D. Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Mutagenesis 219 – 219 L -> F. Decreased protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Mutagenesis 223 – 223 Q -> R. Abolishes protease activity with APP.
Mutagenesis 226 – 226 L -> F. Increases protease activity with APP.
Mutagenesis 230 – 230 S -> I. Abolishes protease activity with APP.
Mutagenesis 238 – 238 I -> M. Abolishes protease activity with APP.
Mutagenesis 239 – 239 K -> N. Abolishes protease activity with APP.
Helix 219 – 239



Literature citations
Early-onset Alzheimer's disease caused by a novel mutation at codon 219 of the presenilin-1 gene.
Smith M.J.; Gardner R.J.; Knight M.A.; Forrest S.M.; Beyreuther K.; Storey E.; McLean C.A.; Cotton R.G.; Cappal R.; Masters C.L.;
NeuroReport 10:503-507(1999)
Cited for: VARIANT AD3 PRO-219;
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.