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UniProtKB/Swiss-Prot P29120: Variant p.Asn221Asp

Neuroendocrine convertase 1
Gene: PCSK1
Variant information

Variant position:  221
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 Asparagine (N) to Aspartate (D) at position 221 (N221D, p.Asn221Asp).
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 acidic (D)
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

Polymorphism:  Genetic variations in PCSK1 define the body mass index quantitative trait locus 12 (BMIQ12) [MIM:612362]. Variance in body mass index is a susceptibility factor for obesity.
Additional information on the polymorphism described.

Variant description:  Associated with susceptibility to obesity; induces a 10.4% reduction of activity (P = 0.03) when compared to the wild-type enzyme.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  221
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  753
The length of the canonical sequence.

Location on the sequence:   DPTNENKHGTRCAGEIAMQA  N NHKCGVGVAYNSKVGGIRML
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.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         DPTNENKHGTRCAGEIAMQANNHKCGVGVAYNSKVGGIRML

Mouse                         DLTNENKHGTRCAGEIAMQANNHKCGVGVAYNSKVGGIRML

Rat                           DPTNENKHGTRCAGEIAMQANNHKCGVGVAYNSKVGGIRML

Bovine                        DLINENKHGTRCAGEIAMQANNHKCGVGVAYNSKVGGIRML

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 111 – 753 Neuroendocrine convertase 1
Domain 129 – 450 Peptidase S8
Active site 208 – 208 Charge relay system


Literature citations

Characterization of single-nucleotide polymorphisms in coding regions of human genes.
Cargill M.; Altshuler D.; Ireland J.; Sklar P.; Ardlie K.; Patil N.; Shaw N.; Lane C.R.; Lim E.P.; Kalyanaraman N.; Nemesh J.; Ziaugra L.; Friedland L.; Rolfe A.; Warrington J.; Lipshutz R.; Daley G.Q.; Lander E.S.;
Nat. Genet. 22:231-238(1999)
Cited for: VARIANTS ASP-221; GLU-665 AND THR-690;

Common nonsynonymous variants in PCSK1 confer risk of obesity.
Benzinou M.; Creemers J.W.M.; Choquet H.; Lobbens S.; Dina C.; Durand E.; Guerardel A.; Boutin P.; Jouret B.; Heude B.; Balkau B.; Tichet J.; Marre M.; Potoczna N.; Horber F.; Le Stunff C.; Czernichow S.; Sandbaek A.; Lauritzen T.; Borch-Johnsen K.; Andersen G.; Kiess W.; Koerner A.; Kovacs P.; Jacobson P.; Carlsson L.M.S.; Walley A.J.; Joergensen T.; Hansen T.; Pedersen O.; Meyre D.; Froguel P.;
Nat. Genet. 40:943-945(2008)
Cited for: VARIANT ASP-221; CHARACTERIZATION OF VARIANT ASP-221; POLYMORPHISM;

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.