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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49768: Variant p.Ala79Val

Presenilin-1
Gene: PSEN1
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Variant information Variant position: help 79 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 Alanine (A) to Valine (V) at position 79 (A79V, p.Ala79Val). 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 small size and hydrophobic (A) to medium size and hydrophobic (V) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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; also found in late-onset Alzheimer disease; impaired protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; no effect on interaction with GFAP. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 79 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 SRQVVEQDEEEDEELTLKYG A KHVIMLFVPVTLCMVVVVAT 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 1 – 82 Cytoplasmic
Mutagenesis 82 – 82 V -> KE. Loss of interaction with GFAP.
Mutagenesis 99 – 99 T -> A. Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Helix 74 – 102



Literature citations
A new splice variant of glial fibrillary acidic protein GFAPepsilon, interacts with the presenilin proteins.
Nielsen A.L.; Holm I.E.; Johansen M.; Bonven B.; Jorgensen P.; Jorgensen A.L.;
J. Biol. Chem. 277:29983-29991(2002)
Cited for: INTERACTION WITH GFAP; MUTAGENESIS OF 66-ASP--ASP-72; 76-LYS-TYR-77; 82-VAL-ILE-83; VAL-82 AND 84-MET-LEU-85; CHARACTERIZATION OF VARIANTS AD3 VAL-79 AND LEU-82; Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease.
Cruts M.; van Duijn C.M.; Backhovens H.; van den Broeck M.; Wehnert A.; Serneels S.; Sherrington R.; Hutton M.; Hardy J.; St George-Hyslop P.H.; Hofman A.; van Broeckhoven C.;
Hum. Mol. Genet. 7:43-51(1998)
Cited for: VARIANTS AD3 VAL-79; CYS-115 AND VAL-231; VARIANT GLY-318; High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes.
Finckh U.; Mueller-Thomsen T.; Mann U.; Eggers C.; Marksteiner J.; Meins W.; Binetti G.; Alberici A.; Hock C.; Nitsch R.M.; Gal A.;
Am. J. Hum. Genet. 66:110-117(2000)
Cited for: VARIANTS AD3 VAL-79; LEU-105 AND VAL-139; 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; 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; Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer's disease presenilin 1 mutation.
Kauwe J.S.; Jacquart S.; Chakraverty S.; Wang J.; Mayo K.; Fagan A.M.; Holtzman D.M.; Morris J.C.; Goate A.M.;
Ann. Neurol. 61:446-453(2007)
Cited for: VARIANT AD3 VAL-79; CHARACTERIZATION OF VARIANT AD3 VAL-79; 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.