TABLE 4.
Major human drug-metabolizing cytochrome P450 enzymesa
| CYP | Chromosome | Expression | Relative protein abundance in liver (%) | % of drugs metabolized by enzyme (antifungal drugs) | Major variant allele(s) | Mutation | Consequence |
|---|---|---|---|---|---|---|---|
| CYP1A1 | 15q22-q24 | Inducible | <1 | CYP1A1*2A&B | 3801T>C I462V | Increased inducibility Increased activity | |
| CYP1A2 | 15q22qter | Inducible | 8-15 | 11 (terbinafine) | CYP1A2*1F | −164C>A | Higher inducibility |
| CYP2A6 | 19q13.2 | Constitutive | 5-12 | 3 | CYP2A6*2 | L160H | Inactive enzyme |
| CYP2A6*4 | Gene deletion | No enzyme | |||||
| CYP2A6*9 | TATA-mut | Less enzyme | |||||
| CYP2B6 | 19q13.2 | Inducible? | 1-5 | 3 | CYP2B6*5 | R487C | Less enzyme |
| CYP2B6*7 | Q172H; K262R; R487C | Less enzyme | |||||
| CYP2C8 | 10q24.1 | Constitutive | 10 | CYP2C8*2 | 1269F | Decreased activity | |
| CYP2C8*3 | R139K, K399R | Decreased activity | |||||
| CYP2C8*4 | 1264M | Decreased activity | |||||
| CYP2C9 | 10q24 | Constitutive | 15-20 | 16 (voriconazole, terbinafine) | CYP2C9*2 | R144C | Reduced affinity for P450 reductase |
| CYP2C9*3 | I359L | Altered substrate specificity | |||||
| CYP2C19 | 10q24.1-q24.3 | Constitutive | <5 | 8 (voriconazole, terbinafine) | CYP2C19*2 | Altered splice site | Inactive enzyme |
| CYP2C19*3 | Stop codon | Inactive enzyme | |||||
| CYP2D6 | 22q13.1 | Constitutive | 2 | 19 | CYP2D6*2xn | Gene duplication | Increased activity |
| CYP2D6*4 | Defective splicing | Inactive enzyme | |||||
| CYP2D6*5 | Gene deletion | No enzyme | |||||
| CYP2D6*6 | 1707T>del P34S | No enzyme | |||||
| CYP2D6*10 | S486T T107I | Unstable enzyme | |||||
| CYP2D6*17 | R296C S486T | Reduced affinity for substrates | |||||
| CYP2E1 | 10q24.3-qter | Constitutive/inducible | 7-11 | 4 | CYP2E1*2 | R76H | Less enzyme expressed |
| CYP2E1*3 | V389I | No effects | |||||
| CYP2E1*4 | V179I | No effects | |||||
| CYP3A4 | 7q21.1 | Constitutive | 30-40 | 36 (itraconazole, ketoconazole, voriconazole, terbinafine) | CYP3A4*2 | S222P | Higher Km for substrate |
| CYP3A4*3 | M445T | Unknown | |||||
| CYP3A4*4 | I118V | Decreased | |||||
| CYP3A4*5 | P218R | Decreased | |||||
| CYP3A4*6 | 831 insA | Decreased | |||||
| CYP3A5 | 7q21.1 | Constitutive | <1 | CYP3A5*3 | Splicing defect | No enzyme | |
| CYP3A5*6 | Splicing defect | No enzyme |
a
Modified from reference 68 with permission of the publisher and from reference 215 with permission of Elsevier; includes data from http://www.cypalleles.ki.se.