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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49768: Variant p.Ile143Thr

Presenilin-1
Gene: PSEN1
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Variant information Variant position: help 143 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 Isoleucine (I) to Threonine (T) at position 143 (I143T, p.Ile143Thr). 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 hydrophobic (I) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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

Variant description: help In AD3; impaired protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 143 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 ETVGQRALHSILNAAIMISV I VVMTILLVVLYKYRCYKVIH 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 133 – 153 Helical
Mutagenesis 123 – 123 E -> K. Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Mutagenesis 131 – 131 H -> R. Severe decrease of protease activity with APP.
Mutagenesis 136 – 136 A -> G. Decreased protease activity with APP.
Mutagenesis 143 – 143 I -> V. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Mutagenesis 150 – 150 L -> P. Nearly abolishes protease activity with APP.
Helix 125 – 155



Literature citations
Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3.
Cruts M.; Backhovens H.; Wang S.-Y.; van Gassen G.; Theuns J.; de Jonghe C.; Wehnert A.; de Voecht J.; de Winter G.; Cras P.; Bruyland M.; Datson N.; Weissenbach J.; den Dunnen J.T.; Martin J.-J.; Hendriks L.; Van Broeckhoven C.;
Hum. Mol. Genet. 4:2363-2372(1995)
Cited for: VARIANTS AD3 THR-143 AND ALA-384; Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia.
Arango D.; Cruts M.; Torres O.; Backhovens H.; Serrano M.L.; Villareal E.; Montanes P.; Matallana D.; Cano C.; Van Broeckhoven C.; Jacquier M.;
Am. J. Med. Genet. 103:138-143(2001)
Cited for: VARIANTS AD3 MET-94; THR-143 AND ALA-280; VARIANT GLY-318; Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations.
Rogaeva E.A.; Fafel K.C.; Song Y.Q.; Medeiros H.; Sato C.; Liang Y.; Richard E.; Rogaev E.I.; Frommelt P.; Sadovnick A.D.; Meschino W.; Rockwood K.; Boss M.A.; Mayeux R.; St George-Hyslop P.;
Neurology 57:621-625(2001)
Cited for: VARIANTS AD3 GLN-35; VAL-79; CYS-115; ASN-116; THR-143; ILE-146; LEU-146; VAL-146; TYR-156 DELINS PHE-THR-TYR; ARG-163; LEU-177; SER-177; PRO-178; ALA-206; SER-206; GLU-209; LEU-213; ARG-222; THR-231; LEU-233; PRO-235; PHE-261; ARG-274; ARG-352 INS; ILE-354; GLN-358; TYR-365; VAL-394; PHE-418; GLU-431; PHE-435 AND VAL-439; VARIANT GLY-318; A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques.
Dermaut B.; Kumar-Singh S.; Engelborghs S.; Theuns J.; Rademakers R.; Saerens J.; Pickut B.A.; Peeters K.; van den Broeck M.; Vennekens K.; Claes S.; Cruts M.; Cras P.; Martin J.J.; Van Broeckhoven C.; De Deyn P.P.;
Ann. Neurol. 55:617-626(2004)
Cited for: VARIANT PIDB VAL-183; CHARACTERIZATION OF VARIANTS AD3 THR-143 AND VAL-282; CHARACTERIZATION OF VARIANT PIDB VAL-183; Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40.
Kumar-Singh S.; Theuns J.; Van Broeck B.; Pirici D.; Vennekens K.; Corsmit E.; Cruts M.; Dermaut B.; Wang R.; Van Broeckhoven C.;
Hum. Mutat. 27:686-695(2006)
Cited for: CHARACTERIZATION OF VARIANTS AD3 VAL-79; THR-143; VAL-231; PHE-262; PHE-263; VAL-282 AND ALA-384; Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Abeta42 and Abeta40 peptides by gamma-secretase.
Sun L.; Zhou R.; Yang G.; Shi Y.;
Proc. Natl. Acad. Sci. U.S.A. 114:E476-E485(2017)
Cited for: CHARACTERIZATION OF VARIANTS AD3 GLN-35; VAL-79; LEU-82; PRO-85; LEU-89; SER-92; MET-94; PHE-96; LEU-97; HIS-115; ASN-116; ASP-120; LYS-120; ARG-134; ASP-135; VAL-139; THR-143; LEU-146; ILE-147; VAL-153; ASN-154; ARG-163; TYR-163; PRO-166; PRO-169; PHE-170; PRO-171; TRP-173; MET-174; LEU-177; PRO-178; VAL-183; ASP-184; ALA-206; SER-206; ARG-209; VAL-209; LEU-213; ARG-217; ARG-222; PHE-229; THR-231; LEU-233; THR-233; ARG-235; PRO-235; VAL-235; ILE-237; GLU-246; SER-250; VAL-260; PHE-261; PHE-262; ARG-263; LEU-264; SER-266; SER-267; GLY-269; VAL-271; ARG-274; VAL-275; ALA-280; GLY-280; ARG-282; VAL-285; VAL-286; ILE-354; GLN-358; GLU-378; VAL-378; VAL-381; ALA-384; ILE-390; VAL-392; VAL-394; THR-396; SER-405; THR-409; TYR-410; PHE-418; PRO-426; GLU-431; PHE-435; SER-436 AND VAL-439; CHARACTERIZATION OF VARIANT CMD1U GLY-333; MUTAGENESIS OF THR-99; PHE-105; ARG-108; LEU-113; PRO-117; GLU-123; HIS-131; ALA-136; ILE-143; LEU-150; TRP-165; ILE-168; PHE-176; GLU-184; ILE-202; SER-212; HIS-214; LEU-219; GLN-223; LEU-226; SER-230; ILE-238; LYS-239; THR-245; LEU-248; TYR-256; VAL-272; GLU-273; ARG-278; PRO-284; THR-291; ARG-352; SER-365; ARG-377; PHE-386; VAL-391; VAL-412; LEU-420; LEU-424; ALA-434 AND ILE-437;
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.