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Genetic Archaeology
GENETIC ARCHAEOLOGY // PROFILE

CYP2D6

Cytochrome P450 2D6

CHR 22
22q13.2

Overview

CYP2D6 is a member of the cytochrome P450 enzyme family. It is primarily active in the liver and is responsible for the breakdown of approximately 20-25% of clinically used drugs. Due to strong genetic variations, individuals metabolize drugs extremely differently – from almost not at all (Poor Metabolizer) to extremely fast (Ultrarapid Metabolizer).

📍 Chromosomal Position

22q13.2 (Chromosome 22)

đŸ§Ŧ Gene Category

Metabolism

đŸ”Ŧ Inheritance

Autosomal codominant

📊 Prevalence (PM)

7-10% (Europeans)

Function & Significance

The CYP2D6 enzyme processes substances such as antidepressants (e.g., SSRIs), beta-blockers, antiarrhythmics, and painkillers (e.g., codeine, tramadol). For codeine, CYP2D6 is responsible for converting the drug into active morphine.

â„šī¸ Personalized Medicine

Knowledge of CYP2D6 status allows physicians to tailor drug dosages individually. “Poor Metabolizers” risk severe side effects at standard doses, while “Ultrarapid Metabolizers” often feel no effect because the body eliminates the active ingredient too quickly (or, in the case of codeine, converts it too quickly into toxic amounts of morphine).

đŸ§Ŧ Relevant SNP

One of the most common function-reducing variants (CYP2D6*4):

rs3892097
22:42128945
Allele 1

G

/

Allele 2

A

CYP2D6*4 (G>A):
This is a splice-site mutation (G>A) resulting in an inactive enzyme. Individuals with the AA genotype are “Poor Metabolizers.”

📚 Data Sources

  • OMIM: #124030 – Cytochrome P450, Subfamily IID, Polypeptide 6; CYP2D6
  • PharmGKB: Gene-Specific Information for CYP2D6
  • CPIC: Clinical Pharmacogenetics Implementation Consortium Guidelines

Biological Function

The enzyme is responsible for the metabolism of about 25% of all clinically relevant drugs. Genetic variants lead to extremely different metabolic rates (Poor, Intermediate, Extensive, and Ultrarapid Metabolizers).

Associated Conditions

Drug Intolerance Therapy Failure Toxicity at Standard Dosage
Molecular Analysis

Analyzed Markers

rs3892097 Pharmacogenetic
Pos: 22:42128945 | Alleles: G/A

CYP2D6*4 - Most common variant leading to complete loss of enzyme function (Poor Metabolizer).