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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49768: Variant p.His214Tyr

Presenilin-1
Gene: PSEN1
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Variant information Variant position: help 214 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help US 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 Histidine (H) to Tyrosine (Y) at position 214 (H214Y, p.His214Tyr). 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 Change from medium size and polar (H) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 2 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 Found in a patient with dementia; uncertain significance. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 214 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 DYITVALLIWNFGVVGMISI H WKGPLRLQQAYLIMISALMA 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
Transmembrane 195 – 216 Helical
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.
Helix 195 – 214



Literature citations
Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients.
Lohmann E.; Guerreiro R.J.; Erginel-Unaltuna N.; Gurunlian N.; Bilgic B.; Gurvit H.; Hanagasi H.A.; Luu N.; Emre M.; Singleton A.;
Neurobiol. Aging 33:1850.E17-1850.E27(2012)
Cited for: VARIANTS AD3 ARG-134; ARG-163 AND VAL-262; VARIANT TYR-214;
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.