GENETIC POLYMORPHISMS OF CYTOCHROME P450 (CYP) 2D6 ©2011 Pharmacology Weekly, Inc.
Allele	Population	Single Nucleotide Polymorphism	Location	CYP2D6 Activity	Notes
CYP2D6*1	General Population	Wild-type; 5,139bp	22q13.1	normal	Extensive metabolizer
CYP2D6*2xn	Ethiopians/Saudi Arabian 10-16% Caucasians 1-5%   Asians 0-2%	Gene duplication C2983T (R296C) G4268C (S486T)	Exon 6 Exon 9	↑	Ultra-rapid or extensive metabolizer
CYP2D6*3	Asians 0%	1-bp deletion 2637A or (aka., 2549A)	Exon 5	absent	Poor metabolizer due to frame shift mutation
CYP2D6*4	African Americans 2%	G1934A	Junction of Intron 3 & Exon 4	absent	Poor to no metabolic activity due to a splicing defect
CYP2D6*5	Caucasians 0.04% African Americans 4%	11.5-kb deletion on gene	On allele	absent	No 2D6 enzyme present in liver
CYP2D6*6	Caucasians 1.8%	Deletion of T-1795 causing a premature stop codon	Exon 3	absent	Poor metabolizer non- functioning variant
CYP2D6*9	NR	AGA deletion at 2613-2615 (K281)	-	↓/↔	Poor metabolizer
CYP2D6*10	Asians 39-51% African American 6% Caucasians 1-2%	C188T; also seen as C100T (P34S)	Exon 1	↓	Intermediate metabolizer
CYP2D6*14	Asian 2.2%	P34S G169R R296C S486T	Exon 3	absent	Poor metabolizer; non- functional enzyme
CYP2D6*17	African Americans 20-35%	C111T (T107I) C2938T (R296S) G4268C (S486T)	Intron 1	↓	Altered affinity for substrates of 2D6
CYP2D6*29	Black Africans 20%	G3183A	-	↓	Poor metabolizer
CYP2D6*41	Caucasians 8-10% African American 11% Japanese 2.6%	G2988A	Intron 6	↓	Intermediate metabolizer due to aberrant splicing

The letters  before and after the numbers represent the single nucleotides that make up the DNA sequence and codons to code for an amino acid (A = adenine, C = cytosine, G = guanine, T = thymine).  Amino acids represented: (C = cysteine, G = glycine, K = lysine, P = proline, R = arginine, S = serine, T = threonine, V = valine).  NR = not reported.

MEDICATIONS AFFECTED:

See Substrates for CYP2D6 in the Drug Tables.


REFERENCES:

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