An inactive cytochrome P450 CYP2D6 allele containing a deletion and a base substitution.

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Daly AK, Leathart JB, London SJ, Idle JR

An inactive cytochrome P450 CYP2D6 allele containing a deletion and a base substitution.

Hum Genet. 1995 Mar;95(3):337-41.

PubMed ID

7868129 [ View in PubMed

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Abstract

The cytochrome P450 CYP2D6 is a polymorphic enzyme, for which 5%-10% of Caucasians (poor metabolizers) lack activity. The majority of mutations giving rise to the deficiency have now been identified but some individuals show anomalous phenotype-genotype relationships when screened for the common mutant alleles. We have sequenced all nine exons and intron-exon boundaries in a subject who was phenotypically a poor metabolizer but genotypically heterozygous when screened for the common alleles. A single base-pair deletion (T1795) was detected in exon 3 and a base substitution (G2064A) resulting in an amino acid substitution (G212E) in exon 4. The deletion results in premature termination of translation and a truncated protein. In a group of 50 white Americans, the allele frequency for the new mutant allele was 0.01. The new allele explains some cases of anomalous genotype/phenotype relationships for CYP2D6.

DrugBank Data that Cites this Article

Polypeptides

Name	UniProt ID
Cytochrome P450 2D6	P10635	Details

Pharmaco-genomics

Drug	Interacting Gene/Enzyme	Allele name	Genotypes	Defining change(s)	Type(s)	Description	Details
Metoprolol	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*6	Not Available	1707delT (rs5030655)	ADR Inferred	Increased risk of slow heart rate (bradycardia)	Details
Amitriptyline	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*6	Not Available	1707delT (rs5030655)	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Imipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*6	Not Available	1707delT (rs5030655)	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Nortriptyline	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*6	Not Available	1707delT (rs5030655)	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Tamoxifen	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*6	Not Available	1707delT (rs5030655)	Effect Inferred	Poor response to drug treatment, shorter time to relapse	Details
Desipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*6	Not Available	1707delT (rs5030655)	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details
Clomipramine	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*6	Not Available	1707delT (rs5030655)	Effect Inferred	Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects	Details