CYP2C19*3 AND Proguanil, poor metabolism of

Clinical significance:drug response (Last evaluated: Jun 1, 2009)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000018398.28

Allele description [Variation Report for CYP2C19*3]

NM_000769.1(CYP2C19):c.636G>A (p.Trp212Ter)

Gene:
CYP2C19:cytochrome P450 family 2 subfamily C member 19 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q23.33
Genomic location:
Preferred name:
NM_000769.1(CYP2C19):c.636G>A (p.Trp212Ter)
Other names:
CYP2C19, TRP212TER (rs4986893); CYP2C19m2; CYP2C19*3
HGVS:
  • NC_000010.11:g.94780653G>A
  • NG_008384.3:g.22973G>A
  • NM_000769.4:c.636G>AMANE SELECT
  • NP_000760.1:p.Trp212Ter
  • NC_000010.10:g.96540410G>A
  • NM_000769.2:c.636G>A
Protein change:
W212*; TRP212TER
Links:
Genetic Testing Registry (GTR): GTR000569665; PharmGKB: 981201917; PharmGKB: 981201917PA449053; PharmGKB Clinical Annotation: 981201917; OMIM: 124020.0003; dbSNP: rs4986893
NCBI 1000 Genomes Browser:
rs4986893
Molecular consequence:
  • NM_000769.4:c.636G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Proguanil, poor metabolism of
Identifiers:
MedGen: C1836026

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000038680OMIMno assertion criteria provideddrug response
(Jun 1, 2009)
germlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese.

De Morais SM, Wilkinson GR, Blaisdell J, Meyer UA, Nakamura K, Goldstein JA.

Mol Pharmacol. 1994 Oct;46(4):594-8.

PubMed [citation]
PMID:
7969038

High frequencies of CYP2C19 mutations and poor metabolism of proguanil in Vanuatu.

Kaneko A, Kaneko O, Taleo G, Björkman A, Kobayakawa T.

Lancet. 1997 Mar 29;349(9056):921-2. No abstract available.

PubMed [citation]
PMID:
9093256
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000038680.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

This allelic variant is also known as CYP2C19*3 and CYP2C19m2.

De Morais et al. (1994) identified a G-to-A mutation at nucleotide 636 in exon 4 of the CYP2C19 gene in Japanese poor metabolizers (609535). The mutation resulted in a premature termination codon (trp212 to ter; W212X).

Using PCR, Kaneko et al. (1997) determined the distribution of the CYP2C19*2 (124020.0001) and CYP2C19*3 mutations in 493 individuals from 2 of the 80 islands of Vanuatu, where malaria is endemic. The CYP2C19*2 allele represented 698 of 986 alleles (70.6%), and the CYP2C19*3 allele represented 131 of 986 alleles (13.3%). Only 145 individuals had at least 1 wildtype allele. Further studies showed that homozygosity or compound heterozygosity for the mutations were associated with poor metabolism of proguanil, which is recommended for malaria chemoprophylaxis. The data suggested that 348 of the 493 individuals (70.6%) studied had the poor metabolizer phenotype, a finding with major implications for the efficacy of proguanil in this population.

In a population-based study of 359 unrelated mainland Chinese, consisting of 103 Han, 107 Kazakh, and 149 Uygur individuals, Wang et al. (2009) found that the frequencies of the CYP2C19*3 allele were similar among the 3 groups (7.2%, 8.0%, and 9.4%, respectively) and higher than that reported in Caucasians (0%).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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