CYP allele designation*a Key mutation(s)*b rs number Location, protein
effect
CYP1A1*2C 2454A>G (rs1048943) I462V
CYP1A2*1C −3860G>A (rs2069514) Promoter
CYP1A2*1F −163C>A (rs762551) Intron 1
142C>G (rs10012); 355G>T
CYP1B1*6 (rs1056827); 4326C>G R48G A119S L432V
(rs1056836)
CYP2A6*2 1799T>A (rs1801272) L160H
CYP2A6*4A to *4H Recombination CYP2A6 deleted
CYP2A6*7 6558T>C (rs5031016) I471T
CYP2A6*9 −48T>G (rs28399433) Promoter, TATA-box
CYP2A6*17 5065G>A (rs28399454) V365M
CYP2B6*4 18053A>G (rs2279343) K262R (isolated)
CYP2B6*5 25505C>T (rs3211371) R487C
CYP2B6*5 25505C>T (rs3211371) R487C
15631G>T (rs3745274);
CYP2B6*6 Q172H K262R
18053A>G (rs2279343)
CYP2B6*18 21011T>C (rs28399499) I328T
CYP2B6*22 −82T>C (rs34223104) Promoter, TATA-box
CYP2C8*2 11054A>T (rs11572103) I269F
2130G>A (rs11572080);
CYP2C8*3 30411A>G (rs10509681) R139K K399R
CYP2C8*4 11041C>G (rs1058930) I264M
CYP2C9*2 3608C>T (rs1799853) R144C
CYP2C9*3 42614A>C (rs1057910) I359L
CYP2C19*2 19154G>A (rs4244285) Splicing defect
CYP2C19*3 17948G>A (rs4986893) W212X
CYP2C19*17 −806C>T (rs12248560) Promoter
CYP2C19*17 −806C>T (rs12248560) Promoter
CYP2D6*3 2549delA (rs35742686) Frameshift
CYP2D6*4 1846G>A (rs3892097) Splicing defect
CYP2D6*5 Recombination Deletion
CYP2D6*6 1707delT (rs5030655) Frameshift
CYP2D6*10 100C>T (rs1065852) P34S
1023C>T (rs28371706);
CYP2D6*17 T107I R296C
2850C>T (rs16947)
CYP2D6*41 2988G>A (rs28371725) Splicing defect
CYP2D6*Nxn Recombination Copy number variations
SP1-binding to promoter
CYP2J2*7 −76G>T (rs890293)
decreased
CYP3A4*1B −392A>G (rs2740574) Promoter
CYP3A4*22 15389 C>T (rs35599367) Intron 6
CYP3A5*3 6986A>G (rs776746) Intron 3, splicing defect
Exon 6, K208, splicing
CYP3A5*6 14690A>G (rs10264272)
defect
POR*28 31696C>T (rs1057868) A503V
POR*28 31696C>T (rs1057868) A503V
Allele frequenciesc Functional effect
gMAF 0.120
0.0–0.04 Af, AA
0.20–0.26 As ↑ Activity (17β-estradiol and
0.03–0.07 Ca estrone)
0.18–0.43 Hs
0.17 Pc
gMAF 0.188
0.26–0.40 AA, Af
0.21–0.27 As, Pc ↓ Inducibility (smokers)
0.01–0.08 Ca
0.20–0.30 Hs
gMAF 0.35 (A > C) ↑ Inducibility (smokers,
0.5–0.8 all ethnicities omeprazole)
gMAF 0.32–39
0.5–0.85 AA, Af ↑ Km, ↓ Vmax (17β-estradiol,
0.09–0.13 As recombinant)
0.23–0.40 Ca
gMAF 0.013
0.00–0.01 AA, Af
No activity
0.00–0.025 As
0.04–0.10 Ca
0.01–0.02 AA
0.05–0.24 As Null allele
0.01–0.04 Ca
gMAF 0.04
0.00 AA, Af
↓ Activity
0.06–0.13 As
0.00 Ca
gMAF 0.13
0.04–0.12 AA, Af
↓ Activity
0.16–0.27 As
0.04–0.05 Ca
gMAF 0.025
0.04–0.50 AA, Af
↓ Activity
0.00 As
0.00–0.02 Ca
gMAF 0.26
0.00 AA, Af
↑ Expression & activity
0.05–0.12 As
0.04 Ca
gMAF 0.05
0.01–0.04 AA, Af
↓ Expression & activity
↓ Expression & activity
0.01–0.04 As
0.09–0.12 Ca
gMAF 0.27 ↓ Expression
0.33–0.5 AA, Af ↓ Activity (efavirenz, nevirapine)
0.10–0.21 As ↑ Activity (cyclophosphamide)
0.14–0.27 Ca
0.62 Pc
gMAF 0.02
0.04–0.08 AA
0.05–0.12 Af ↓↓ Expression & activity
0.01 Hs
0.00 As, Ca, Pc
gMAF 0.012 ↑ Expression & activity
0.00–0.025 AA, Af, As 0.024 Ca, Hs ↑ Inducibility
gMAF 0.039
0.10–0.22 AA, Af ↓ Activity
0.00 As, Ca
gMAF 0.065 ↓ Activity (paclitaxel)
0.00 AA, Af, As ↑ Activity (antidiabetics)
0.65–0.14 Ca, Hs
gMAF 0.026
0.00–0.01 AA, Af, As, Pc ↓ Activity (paclitaxel)
0.03–0.07 Ca, Hs
gMAF 0.069
0.00–0.02 AA, Af
0.00–0.02 As, Pc ↓ Activity
0.10–0.17
Ca 0.065 Hs
gMAF 0.043
0.00–0.01 Af, AA
↓↓ Activity
0.02–0.06 As
0.06 Ca
gMAF 0.199
0.10–0.17 AA, Af
0.22–0.32 As, Pc Null allele
0.06–0.15 Ca
0.15 Hs
gMAF 0.014
0.00–0.01 Af, Ca, Hs Null allele
0.03–0.07 As, Pc
gMAF 0.15
0.15–0.27 AA, Af
↑ Expression & activity
0.00–0.02 As
↑ Expression & activity
0.21–0.25 Ca
gMAF 0.009
Null allele
~0.01 all ethnicities
gMAF 0.106
0.01–0.10 AA, Af, As, Hs Null allele
0.15–0.25 Ca
0.03–0.06 all ethnicities Null allele
gMAF 0.01
Null allele
~0.01 all ethnicities
gMAF 0.26
0.08–0.12 AA, Af
↓ Expression & activity
0.40–0.70 As
0.02 Ca
gMAF 0.049 (for 1023C>T)
0.14–0.24 Af ↓ Expression & activity
0.00 As, Ca
gMAF 0.055
0.01–0.06 Af, As, Pc, Hs ↓ Expression & activity
0.09 Ca
Up to 0.30 Af, Ar
↑ Expression & activity
0.01–0.09 Ca
gMAF 0.073
0.10–0.17 AA, Af
↓ Expression & activity
0.02–0.13 As
0.055–0.08 Ca
gMAF 0.20
0.50–0.82 AA, Af
Probably no effect on transcription
0.00 As
0.03–0.05 Ca, Hs, SA
gMAF 0.021
0.043 AA
↓ Expression & activity
0.043 As
0.025–0.08 Ca
gMAF 0.312
0.37 AA
0.12–0.35 Af ↓↓ Expression & activity
0.66–0.75 As, Hs
0.88–0.97 Ca
gMAF 0.045
0.15–0.25 Af
↓↓ Expression & activity
0.12 AA
0.00 As, Ca, His
gMAF 0.287
0.08–0.50 AA, Af
Various substrate- and CYP-
0.38–0.42 As
dependent effects in vitro
Various substrate- and CYP-
dependent effects in vitro
0.29–0.33 Ca
0.32–0.35 Pc
Clinical correlations
↑ Lung cancer risk in Chinese; ↑ breast cancer risk in
Caucasians; ↑ prostate cancer risk
May influence susceptibility to certain cancers
↑ Susceptibility to cancer in Caucasians; ↑ oral clearance
olanzapine; possible modifier for risk of coronary heart
disease
↑ Prostate cancer risk for L432V in Asians
↓ Nicotine metabolism & influence on cigarette
consumption, nicotine dependence, smoking cessation
response; ↑ lung cancer risk in Caucasians; ↓ oral
clearance of tegafur
↑ Drug clearance (bupropion, efavirenz,
cyclophosphamide)
Possibly decreased drug clearance
Possibly decreased drug clearance
↓ Drug clearance & ↑ adverse events including treatment
discontinuation (efavirenz, nevirapine, S-methadone)
Possibly increased drug clearance
Controversial clinical effects
↓ Drug clearance & ↑ risk of bleeding (anticoagulants
warfarin, acenocoumarol, phenprocoumone); ↓ drug
clearance & ↑ adverse events (sulfonylurea hypoglycemic
drugs, NSAIDS); ↓ drug clearance & ↑ adverse events
(sulfonylurea hypoglycemic drugs, NSAIDS)
↓ Clearance & ↑ efficacy of PPIs in Helicobacter
pylori eradication therapy; ↓ anticoagulation effect of
clopidogrel & ↑ cardiovascular events; ↓ clearance & ↑
risk of ADRs for antidepressants (amitriptypine,
citalopram, clomipramine, moclobemide), antimalarials
(proguanil), antifungals (voriconazole)
↑ Clearance of PPIs & risk of subtherapeutic
concentrations; ↑ risk of bleeding with clopidogrel
↑ Clearance of PPIs & risk of subtherapeutic
concentrations; ↑ risk of bleeding with clopidogrel
↓ Clearance & ↑ risk of ADRs for many antiarrhythmics,
antidepressants, antipsychotics; ↓ metabolic activation &
analgesic effect of opioids (codeine, dihydrocodeine,
oxycodone, tramadol); ↓ metabolic activation & efficacy
of tamoxifen
↑ Toxicity of opioids
No conclusive clinical associations
↑ Prostate cancer disease progression
↓ Metabolism of simvastatin & ↑ lipid-lowering
response; ↓ daily-dose requirement for tacrolimus
↓ Metabolism & dose requirements for selected drugs
with a preference for metabolism by CYP3A5 over
CYP3A4 (e.g., tacrolimus, saquinavir)
↓ Enzyme activity of major CYP enzymes in patients with
rare POR deficiency; ↑ CYP3A4 enzyme activity with
midazolam
↓ Enzyme activity of major CYP enzymes in patients with
rare POR deficiency; ↑ CYP3A4 enzyme activity with
midazolam
