UniProtKB/Swiss-Prot P49768: Variant p.Ile143Thr

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 143 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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: 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: 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: -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: 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: Links to websites of interest for the variant.

• Variant rs63750004 [ dbSNP | Ensembl ]

Sequence information

Variant position: 143 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 467 The length of the canonical sequence.
Location on the sequence: 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: 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.

Type	Positions	Description
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;