UniProtKB/Swiss-Prot P49768: Variant p.His163Arg

Presenilin-1
Gene: PSEN1
Chromosomal location: 14q24.3
Variant information

Variant position:  163
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Histidine (H) to Arginine (R) at position 163 (H163R, p.His163Arg).
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 (H) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  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:  In AD3.
Any additional useful information about the variant.



Sequence information

Variant position:  163
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:   IVVMTILLVVLYKYRCYKVI  H AWLIISSLLLLFFFSFIYLG
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.

TypePositionsDescription
Chain 1 – 298 Presenilin-1 NTF subunit
Transmembrane 161 – 181 Helical
Alternative sequence 162 – 184 IHAWLIISSLLLLFFFSFIYLGE -> SMRHRSLLSTLFFLWLGILVTVT. In isoform 4.


Literature citations

Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.
Sherrington R.; Rogaev E.I.; Liang Y.; Rogaeva E.A.; Levesque G.; Ikeda M.; Chi H.; Lin C.; Li G.; Holman K.; Tsuda T.; Mar L.; Foncin J.-F.; Bruni A.C.; Montesi M.P.; Sorbi S.; Rainero I.; Pinessi L.; Nee L.; Chumakov I.; Pollen D.; Brookes A.; Sanseau P.; Polinsky R.J.; Wasco W.; da Silva H.A.R.; Haines J.L.; Pericak-Vance M.A.; Tanzi R.E.; Roses A.D.; Fraser P.E.; Rommens J.M.; St George-Hyslop P.H.;
Nature 375:754-760(1995)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2); VARIANTS AD3 LEU-146; ARG-163; GLU-246 AND VAL-286;

Mutations of the presenilin I gene in families with early-onset Alzheimer's disease.
Campion D.; Flaman J.-M.; Brice A.; Hannequin D.; Dubois B.; Martin C.; Moreau V.; Charbonnier F.; Didierjean O.; Tardieu S.; Penet C.; Puel M.; Pasquier F.; le Doze F.; Bellis G.; Calenda A.; Heilig R.; Martinez M.; Mallet J.; Bellis M.; Clerget-Darpoux F.; Agid Y.; Frebourg T.;
Hum. Mol. Genet. 4:2373-2377(1995)
Cited for: VARIANTS AD3 LEU-82; HIS-115; THR-139; ARG-163; THR-231; LEU-264; VAL-392 AND TYR-410;

Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families.
Kamino K.; Sato S.; Sakaki Y.; Yoshiiwa A.; Nishiwaki Y.; Takeda H.; Tanabe H.; Nishimura T.; Li K.; St George-Hyslop P.H.; Miki T.; Ogihara T.;
Neurosci. Lett. 208:195-198(1996)
Cited for: VARIANTS AD3 PHE-96; ARG-163 AND THR-213;

Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene.
Poorkaj P.; Sharma V.; Anderson L.; Nemens E.; Alonso M.E.; Orr H.; White J.; Heston L.; Bird T.D.; Schellenberg G.D.;
Hum. Mutat. 11:216-221(1998)
Cited for: VARIANTS AD3 ASP-120; ARG-163; VAL-209; VAL-260; LEU-264; TYR-410 AND PRO-426;

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;

Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients.
Lohmann E.; Guerreiro R.J.; Erginel-Unaltuna N.; Gurunlian N.; Bilgic B.; Gurvit H.; Hanagasi H.A.; Luu N.; Emre M.; Singleton A.;
Neurobiol. Aging 33:1850.E17-1850.E27(2012)
Cited for: VARIANTS AD3 ARG-134; ARG-163 AND VAL-262; VARIANT TYR-214;

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.