UniProtKB/Swiss-Prot P49768: Variant p.Glu318Gly

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 318 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B 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 Glutamate (E) to Glycine (G) at position 318 (E318G, p.Glu318Gly). 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 acidic (E) to glycine (G) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -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
Other resources: Links to websites of interest for the variant.

• Variant rs17125721 [ dbSNP | Ensembl ]

Sequence information

Variant position: 318 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: MAEGDPEAQRRVSKNSKYNA E STERESQDTVAENDDGGFSE 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	299 – 467	Presenilin-1 CTF subunit
Topological domain	273 – 380	Cytoplasmic
Region	305 – 333	Disordered
Compositional bias	305 – 329	Basic and acidic residues
Modified residue	310 – 310	Phosphoserine; by PKA
Alternative sequence	185 – 467	Missing. In isoform 4.
Mutagenesis	310 – 310	S -> A. Abolishes PKA-mediated phosphorylation; no effect on caspase-mediated cleavage.

Literature citations

The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer's disease.
Mattila K.M.; Forsell C.; Pirttila T.; Rinne J.O.; Lehtimaki T.; Roytta M.; Lilius L.; Eerola A.; St George-Hyslop P.H.; Frey H.; Lannfelt L.;
Ann. Neurol. 44:965-967(1998)
Cited for: VARIANT GLY-318; Missense mutation E318G of the presenilin-1 gene appears to be a nonpathogenic polymorphism.
Aldudo J.; Bullido M.J.; Frank A.; Valdivieso F.;
Ann. Neurol. 44:985-986(1998)
Cited for: VARIANT GLY-318; 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; The Glu318Gly substitution in presenilin 1 is not causally related to Alzheimer disease.
Dermaut B.; Cruts M.; Slooter A.J.C.; van Gestel S.; de Jonghe C.; Vanderstichele H.; Vanmechelen E.; Breteler M.M.; Hofman A.; van Duijn C.M.; van Broeckhoven C.;
Am. J. Hum. Genet. 64:290-292(1999)
Cited for: VARIANT GLY-318; Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum.
Campion D.; Dumanchin C.; Hannequin D.; Dubois B.; Belliard S.; Puel M.; Thomas-Anterion C.; Michon A.; Martin C.; Charbonnier F.; Raux G.; Camuzat A.; Penet C.; Mesnage V.; Martinez M.; Clerget-Darpoux F.; Brice A.; Frebourg T.;
Am. J. Hum. Genet. 65:664-670(1999)
Cited for: VARIANTS AD3 LEU-82; HIS-115; ASP-120; THR-139; LEU-146; ILE-147; ARG-163; CYS-165; TRP-173; THR-231; THR-233; PRO-235; LEU-264; ILE-390; VAL-392 AND TYR-410; VARIANT GLY-318; DGGE method for the mutational analysis of the coding and proximal promoter regions of the Alzheimer's disease presenilin-1 gene: two novel mutations.
Aldudo J.; Bullido M.J.; Valdivieso F.;
Hum. Mutat. 14:433-439(1999)
Cited for: VARIANTS AD3 LEU-233; ARG-282 AND THR-409; 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; 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; Early onset familial Alzheimer's disease: Mutation frequency in 31 families.
Janssen J.C.; Beck J.A.; Campbell T.A.; Dickinson A.; Fox N.C.; Harvey R.J.; Houlden H.; Rossor M.N.; Collinge J.;
Neurology 60:235-239(2003)
Cited for: VARIANTS AD3 CYS-115; ILE-146; VAL-153; CYS-154; ILE-168 DEL; PRO-171; ASP-184; PHE-229; VAL-235; LEU-237; VAL-260; PHE-263; HIS-269; MET-377 AND VAL-378; VARIANT GLY-318; Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome.
Cornier A.S.; Staehling-Hampton K.; Delventhal K.M.; Saga Y.; Caubet J.-F.; Sasaki N.; Ellard S.; Young E.; Ramirez N.; Carlo S.E.; Torres J.; Emans J.B.; Turnpenny P.D.; Pourquie O.;
Am. J. Hum. Genet. 82:1334-1341(2008)
Cited for: VARIANT GLY-318;