Table 5.
Important variant and allele frequencies of important pharmacogenes in the human CYP3A family
| Allele | Defining variants | Variant type | Allele frequencies in indicated populations (in %) | Functional consequence | ||||
|---|---|---|---|---|---|---|---|---|
| EUR | AFR | EAS | SAS | AMR | ||||
| CYP3A4 | ||||||||
| *1 | None | 91.5 | 96.6 | 97 | 99.1 | 96.9 | Normal | |
| *2 | rs55785340 | Missense (S222P) | 1.1 | 0 | 0 | 0 | 0 | |
| *3 | rs4986910 | Missense (M445T) | 2.1 | 0.1 | 0 | 0 | 0.2 | |
| *4 | rs55951658 | Missense (I118V) | 0 | 0 | 0.6 | <0.1 | <0.1 | |
| *5 | rs55901263 | Missense (P218R) | 0 | 0 | <0.1 | 0 | 0 | |
| *6 | rs4646438 | Frameshift | 0 | 0 | 0.2 | <0.1 | <0.1 | |
| *7 | rs56324128 | Missense (G56D) | 0.1 | 0 | 0 | 0 | 0 | |
| *8 | rs72552799 | Missense (R130Q) | 0.1 | 0 | 0 | <0.1 | <0.1 | Decreaseda |
| *9 | rs72552798 | Missense (V170I) | 0 | 0 | 0 | 0 | <0.1 | |
| *10 | rs4986908 | Missense (D174H) | <0.1 | 0.2 | <0.1 | 0.1 | <0.1 | |
| *11 | rs67784355 | Missense (T363M) | 0 | <0.1 | <0.1 | <0.1 | 0 | Decreaseda |
| *12 | rs12721629 | Missense (L373F) | 0 | 0.3 | 0 | <0.1 | <0.1 | |
| *13 | rs4986909 | Missense (P416L) | 0 | 0 | 0 | 0 | <0.1 | Decreaseda |
| *15 | rs4986907 | Missense (R162Q) | 0 | 2.5 | 0 | <0.1 | 0.2 | |
| *16 | rs12721627 | Missense (T185S) | 0 | 0 | 0.1 | 0 | 0 | Decreaseda |
| *18 | rs28371759 | Missense (L293P) | 0 | 0.2 | 1.9 | 0 | <0.1 | Decreased |
| *19 | rs4986913 | Missense (P467S) | 0 | 0 | 0 | <0.1 | 0 | |
| *20 | rs67666821 | Frameshift | 0 | <0.1 | 0 | 0 | <0.1 | Inactive |
| *22 | rs35599367 | Intronic | 5.0 | <0.1 | 0 | 0.6 | 2.6 | Decreasedb |
| *26 | rs138105638 | Stop‐gain (R268X) | 0 | <0.1 | 0 | <0.1 | <0.1 | Inactive |
| CYP3A5 | ||||||||
| *1 | None | 5.3 | 56.3 | 27.7 | 33.2 | 17.5 | Normal | |
| *2 | rs28365083 | Missense (T398N) | 0.1 | <0.1 | 0 | 0 | <0.1 | |
| *3 | rs776746 | Splicing defect | 94.3 | 18.0 | 71.3 | 66.8 | 79.7 | Inactive |
| *4 | rs56411402 | Missense (Q200R) | 0 | 0 | 0.3 | 0 | 0 | |
| *5 | rs55965422 | Splicing defect | 0 | 0 | 0.7 | <0.1 | 0 | |
| *6 | rs10264272 | Splicing defect | 0.3 | 15.4 | 0 | 0 | 2.3 | Inactive |
| *7 | rs41303343 | Frameshift | 0 | 10.3 | <0.1 | <0.1 | 0.4 | |
| *8 | rs55817950 | Missense (R28C) | 0 | 0 | <0.1 | 0 | 0 | Decreaseda |
AFR, Africans; AMR, admixed Americans; CYP, cytochrome P450; EAS, East Asians; EUR, Europeans; SAS, South Asians.
For references describing the functional characterization of the indicated alleles, see http://www.cypalleles.ki.se.
a
Indicates alleles whose functionality assessment is based solely on in vitro data.
b
Indicates alleles whose functionality assessment is based solely on in vivo data.