UniProtKB/SwissProt variant VAR

Variant information

Variant position:

144

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

Type of variant:

Polymorphism

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Arginine (R) to Histidine (H) at position 144 (R144H, p.Arg144His).

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 large size and basic (R) to medium size and polar (H)

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

Polymorphism:

Genetic variation in CYP2C19 is responsible for poor drug metabolism [MIM:609535]. Individuals can be characterized as either extensive metabolizers (EM) or poor metabolizers (PM). The PM phenotype is inherited in an autosomal recessive manner, with the EM phenotype comprising both homozygous dominant and heterozygote genotypes. There are marked interracial differences in the frequency of this polymorphism. Poor metabolizers represent 2-5% of Caucasians, 13-23% of Asian populations, and as many as 38-79% of individuals of some of the islands of Polynesia and Micronesia. Different alleles of CYP2C19 are known: CYP2C19*1A CYP2C19*1B, CYP2C19*1C, CYP2C19*2A (CYP2C19m1 or CYP2C19m1A), CYP2C19*2B (CYP2C19m1B), CYP2C19*2C (CYP2C19*21), CYP2C19*3A (CYP2C19m2), CYP2C19*3B (CYP2C19*20), CYP2C19*4 (CYP2C19m3), CYP2C19*5A (CYP2C19m4), CYP2C19*5B, CYP2C19*6, CYP2C19*7, CYP2C19*8, CYP2C19*9, CYP2C19*10, CYP2C19*11 CYP2C19*12, CYP2C19*13, CYP2C19*14 CYP2C19*15, CYP2C19*16, CYP2C19*18, CYP2C19*19. Defective CYP2C19*2 and CYP2C19*3 alleles are characterized by a splice mutation and a stop codon, respectively, and account for most of the PM alleles. The sequence shown is that of allele CYP2C19*1B.

Additional information on the polymorphism described.

Variant description:

In allele CYP2C19*9.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs17884712 [ dbSNP | Ensembl ]

Sequence information

Variant position:

144

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

Protein sequence length:

490

The length of the canonical sequence.

Location on the sequence:

RRFSLMTLRNFGMGKRSIED R VQEEARCLVEELRKTKASPC

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 – 490	Cytochrome P450 2C19
Helix	141 – 158

Literature citations

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS LEU-19; ASP-92; ALA-122; HIS-144; ILE-331 AND CYS-410;

Identification and functional characterization of new potentially defective alleles of human CYP2C19.
Blaisdell J.; Mohrenweiser H.; Jackson J.; Ferguson S.; Coulter S.; Chanas B.; Xi T.; Ghanayem B.; Goldstein J.A.;
Pharmacogenetics 12:703-711(2002)
Cited for: VARIANTS PRO-17; LEU-19; HIS-144; HIS-150; LEU-227 AND CYS-410;

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 THR-74; HIS-144; LEU-168 AND ILE-331;

UniProtKB/Swiss-Prot P33261: Variant p.Arg144His