UniProtKB/Swiss-Prot P11509: Variant p.Glu419Asp

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 419 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 Aspartate (D) at position 419 (E419D, p.Glu419Asp). 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: Similar physico-chemical property. Both residues are medium size and acidic. 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
Polymorphism: Genetic variations in CYP2A6 are the cause of altered drug metabolism CYP2A6-related, including metabolism of nicotine, tegafur, and coumarin among others [MIM:621426]. Additional information on the polymorphism described.
Variant description: In allele CYP2A6*28. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs8192730 [ dbSNP | Ensembl ]

Sequence information

Variant position: 419 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 494 The length of the canonical sequence.
Location on the sequence: LRDPSFFSNPQDFNPQHFLN E KGQFKKSDAFVPFSIGKRNC 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 – 494	Cytochrome P450 2A6
Binding site	439 – 439	axial binding residue
Beta strand	419 – 421

Literature citations

Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population.
Saito S.; Iida A.; Sekine A.; Kawauchi S.; Higuchi S.; Ogawa C.; Nakamura Y.;
J. Hum. Genet. 48:249-270(2003)
Cited for: VARIANTS ASP-419 AND THR-471;
Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population.
Solus J.F.; Arietta B.J.; Harris J.R.; Sexton D.P.; Steward J.Q.; McMunn C.; Ihrie P.; Mehall J.M.; Edwards T.L.; Dawson E.P.;
Pharmacogenomics 5:895-931(2004)
Cited for: VARIANTS ARG-5; ASN-29; LEU-118; GLN-128; PRO-224; MET-365; ASP-418; ASP-419; THR-471; ARG-476 AND LEU-485; POLYMORPHISM;
Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent.
Mwenifumbo J.C.; Al Koudsi N.; Ho M.K.; Zhou Q.; Hoffmann E.B.; Sellers E.M.; Tyndale R.F.;
Hum. Mutat. 29:679-688(2008)
Cited for: VARIANTS LEU-110; LEU-118; LEU-128; ALA-131; ASP-418; ASP-419 AND TYR-438; POLYMORPHISM;