UniProtKB/Swiss-Prot P49810: Variant p.Asn141Ile

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 141 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 Asparagine (N) to Isoleucine (I) at position 141 (N141I, p.Asn141Ile). 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 polar (N) to medium size and hydrophobic (I) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -3 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 AD4; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; loss of function as calcium-leak channel; results in calcium overload in the endoplasmic reticulum; increased mitochondrion-endoplasmic reticulum membrane tethering resulting in increased calcium transfer to mitochondria. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs63750215 [ dbSNP | Ensembl ]

Sequence information

Variant position: 141 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 448 The length of the canonical sequence.
Location on the sequence: YTPFTEDTPSVGQRLLNSVL N TLIMISVIVVMTIFLVVLYK 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 – 297	Presenilin-2 NTF subunit
Transmembrane	139 – 159	Helical

Literature citations

Candidate gene for the chromosome 1 familial Alzheimer's disease locus.
Levy-Lahad E.; Wasco W.; Poorkaj P.; Romano D.M.; Oshima J.; Pettingell W.H. Jr.; Yu C.-E.; Jondro P.D.; Schmidt S.D.; Wang K.; Crowley A.C.; Fu Y.-H.; Guenette S.Y.; Galas D.; Nemens E.; Wijsman E.M.; Bird T.D.; Schellenberg G.D.; Tanzi R.E.;
Science 269:973-977(1995)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANT AD4 ILE-141; Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene.
Rogaev E.I.; Sherrington R.; Rogaeva E.A.; Levesque G.; Ikeda M.; Liang Y.; Chi H.; Lin C.; Holman K.; Tsuda T.; Mar L.; Sorbi S.; Nacmias B.; Piacentini S.; Amaducci L.; Chumakov I.; Cohen D.; Lannfelt L.; Fraser P.E.; Rommens J.M.; St George-Hyslop P.H.;
Nature 376:775-778(1995)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS AD4 ILE-141 AND VAL-239; Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations.
Tu H.; Nelson O.; Bezprozvanny A.; Wang Z.; Lee S.F.; Hao Y.H.; Serneels L.; De Strooper B.; Yu G.; Bezprozvanny I.;
Cell 126:981-993(2006)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT AD4 ILE-141; Presenilin 2 modulates endoplasmic reticulum (ER)-mitochondria interactions and Ca2+ cross-talk.
Zampese E.; Fasolato C.; Kipanyula M.J.; Bortolozzi M.; Pozzan T.; Pizzo P.;
Proc. Natl. Acad. Sci. U.S.A. 108:2777-2782(2011)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS AD4 ARG-122 AND ILE-141; MUTAGENESIS OF ASP-366; 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 VARIANT AD4 ILE-141;