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Important Haplotype Information for CYP3A4

Submitted by: Alan Shuldiner (PAPI), Michelle Whirl Carillo, Joan M. Hebert (PharmGKB)
Reviewed by: Under Review
Submitted date: July, 2007

There are 40 Important Haplotypes (Named Alleles) for CYP3A4.

  1. CYP3A4 *1(*1A)
  2. CYP3A4*1B(CYP3A4-V)
  3. CYP3A4*1C
  4. CYP3A4*1D
  5. CYP3A4*1E
  6. CYP3A4*1F
  7. CYP3A4*1G
  8. CYP3A4*1H
  9. CYP3A4*1J
  10. CYP3A4*1K
  11. CYP3A4*1L
  12. CYP3A4*1M
  13. CYP3A4*1N
  14. CYP3A4*1P
  15. CYP3A4*1Q
  16. CYP3A4*1R
  17. CYP3A4*1S
  18. CYP3A4*1T
  19. CYP3A4*2
  20. CYP3A4*3
  21. CYP3A4*4
  22. CYP3A5*5
  23. CYP3A6*6
  24. CYP3A4*7
  25. CYP3A4*8
  26. CYP3A4*9
  27. CYP3A4*10
  28. CYP3A4*11
  29. CYP3A4*12
  30. CYP3A4*13
  31. CYP3A4*14
  32. CYP3A4*15A
  33. CYP3A4*15B
  34. CYP3A4*16A
  35. CYP3A4*16B
  36. CYP3A4*17
  37. CYP3A4*18A
  38. CYP3A4*18B
  39. CYP3A4*19
  40. CYP3A4*20


1. CYP3A4*1A

Gene HGNC
Name: 		CYP3A4
Haplotype
Name: 		CYP3A4*1 (*1A)
Haplotype
 Summary: 		Wild type
Key PubMed
 IDs: 		3267210
Key Variants: NA


2. CYP3A4*1B (CYP3A4-V)

Gene HGNC
Name: 		CYP3A4
Haplotype Name: CYP3A4*1B (CYP3A4-V)
Haplotype Summary: The defining polymorphism for CYP3A4*1B is -392A>G (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . The numbering is in relation to the translation start site; the 'a' of the atg is considered to be +1. This variant is located in the nifedipine-specific response element of the 5-prime promoter region of the CYP3A4 gene.
This allele was first identified by Rebbeck et al. in 1998 [PMID: 9719084]. In the same year Walker et al. reported that this allele was present in 9% of whites, 53% of African-Americans (Black or African American), and was not detected in Taiwanese (Asian) [PMID: 10660343]. The absence of this allele in "Chinese" (Asian) subjects was reported again by Sata et al. and Hsieh et al. [PMID: 10668853, 11181494] and by Ball et al. [PMID: 10511065], who found it to be absent also in Japanese Americans (Asians).

In vitro, this allele has been shown to lead to increased transcription [PMID: 14673875]. A later study [PMID: 12142725] found no such consistent effect in vitro and the authors hypothesized that the effect noted in the first study was an artifact of the expression system used.

This variant was reported to be associated with more malignant characteristics of prostate cancer, particularly in patients 65 years or older with no family history [PMID 10548319, 9719084]. However, it was found later that this association may be attributed to population stratification and that the association with prostate cancer may not be significant [PMID 12107441].

In subjects who were treated with chemotherapeutic agents metabolized by CYP3A and who later developed treatment-related leukemia, a significant deficit of the CYP3A4-V form was found [PMID 9789061]. However, in another study, no association was found between this variant and the development of t-ML in children after treatment for ALL [PMID: 12439220 ] , and a recent study has also failed to find a relationship between the *1B allele and therapy-related leukemia [PMID: 17367411].
The *1B allele was found to be associated with an earlier onset of puberty [PMID: 12692107 ], but no association of this polymorphism with increased risk of breast or ovarian cancer was found in a case-control study of Australian women [PMID: 12142725].
Cancer patients carrying this allele may have a higher rate of docetaxel clearance and so a lower exposure [PMID: 16765145], though the simultaneous presence of CYP3A5*1 in these patients resulted in uncertainty regarding the cause of the higher rate of clearance . There is strong linkage between CYP3A4 *1B and CYP3A5 *1, and it has been suggested that some of the effects originally attributed to CYP3A4 *1B are actually due to CYP3A5 *1 [PMID: 11959896]. However, independent of CYP3A5*1 status, the presence of the CYP3A4*1B allele was shown to increase risk for Small Cell Lung Cancer in women [PMID: 14515059 ] .
In a retrospective study of white female breast cancer patients who had been treated with tamoxifen, Chu et al. recently found that CYP3A4 *1B carriers have an increased risk of developing endometrial cancer when compared with non-*1B carriers [PMID: 17434921]. The authors state that the sample size was small and that this study needs to be confirmed.
Key PubMed IDs: 9719084,10668853,11181494,10945319, 10660343, 14673875, 10548319, 12107441, 9789061,12439220, 16765145, 12142725, 12692107, 14515059 , 11959896 ,17367411, 17434921 , 10511065 , 10334940
Key Variants: -392A>G
(g.61,645 A>G on AF280107 )


3. CYP3A4*1C

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1C
Haplotype Summary: The defining polymorphism for CYP3A4*1C is -444T>G (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This low frequency variant is located in the 5-prime promoter region of the CYP3A4 gene and was first identified by Kuehl et al. in "Caucasians" (Whites) [PMID: 11279519]. No association with altered CYP3A4 enzymatic activity has been observed.
Key PubMed IDs: 11279519
Key Variants: -444T>G
(g.61,593 T>G on AF280107 )


4. CYP3A4*1D

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1D
Haplotype Summary: The defining polymorphism for CYP3A4*1D is -62C>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This low frequency variant is located in the 5-prime promoter region of the CYP3A4 gene and was first identified by Kuehl et al. in Caucasians (Whites) [PMID: 11279519]. No association with altered CYP3A4 enzymatic activity has been observed.
Key PubMed IDs: 11279519
Key Variants:
-62C>A (g.61,975 C>A on AF280107 )


5. CYP3A4*1E

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1E
Haplotype Summary: The defining polymorphism for CYP3A4*1E is -369T>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in the 5-prime promoter region of the CYP3A4 gene and was first identified by Hamzeiy et al. in one Caucasian (White) subject out of 101 DNA samples [PMID: 11890939]. This variant may have some effect on enzyme expression because of its proximity to the CAAT box and other regulatory motifs.
Key PubMed IDs: 11890939
Key Variants: -369T>A
(g.61,668 T>A on AF280107 )


6. CYP3A4*1F

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1F
Haplotype Summary: The defining polymorphism for CYP3A4*1F is -747C>G (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in the 5-prime promoter region of the CYP3A4 gene and was first identified by Hamzeiy et al. with a frequency of 0.2 in "Caucasian" (White) and 0.18 in "Iranian" (White) populations [PMID: 11890939]. This variant is not located in or near a known transcriptional element and might thus have little or no effect on gene expression.
Key PubMed IDs: 11890939
Key Variants: -747C>G
(g.61,290 C>G on AF280107 )


7. CYP3A4*1G

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1G
Haplotype Summary: The defining polymorphism for CYP3A4*1G is 20230G>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in intron 10 of the CYP3A4 gene and was first identified by Dai et al. [PMID: 11714865]. It was also found by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects with a frequency of 0.189 [PMID: 14695543 ].
Key PubMed IDs: 11714865,14695543
Key Variants: 20230G>A
(g.82,266 G>A on AF280107 )


8. CYP3A4*1H

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1H
Haplotype Summary: The defining polymorphisms for CYP3A4*1H are 20230G>A and 26206C>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . The 20230G>A variant is located in intron 10 of the CYP3A4 gene and the 26206C>A variant is located at 3-prime UTR. This allele was first identified by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects with a frequency of 0.010 [PMID: 14695543].
Key PubMed IDs: 14695543
Key Variants: 20230G>A (g.82,266 G>A on AF280107 );
26206C>A (g.88,242 C>A on AF280107 )


9. CYP3A4*1J

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1J
Haplotype Summary: The defining mutation for CYP3A4*1J is 6077A>G (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in intron 3 of the CYP3A4 gene. This allele was first identified by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects with a frequency of 0.004 [PMID: 14695543].
Key PubMed IDs: 14695543
Key Variants: 6077A>G (g.68,113 A>G on AF280107 )


10. CYP3A4*1K

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1K
Haplotype Summary: The defining mutation for CYP3A4*1K is -655A>G (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in the 5-prime promoter region of the CYP3A4 gene. This allele was first identified by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects with a frequency of 0.001 [PMID: 14695543].
Key PubMed IDs: 14695543
Key Variants: -655A>G (g.61,382 A>G on AF280107 )


11. CYP3A4*1L

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1L
Haplotype Summary: The defining mutation for CYP3A4*1L is -630A>G(nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in the 5-prime promoter region of the CYP3A4 gene. This allele was first identified by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects with a frequency of 0.001 [PMID: 14695543].
Key PubMed IDs: 14695543
Key Variants: -630A>G (g.61,407 A>G on AF280107 )


12. CYP3A4*1M

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1M
Haplotype Summary: The defining mutation for CYP3A4*1M is -156C>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in the 5-prime promoter region of the CYP3A4 gene. This allele was first identified by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects with a frequency of 0.001 [PMID: 14695543].
Key PubMed IDs: 14695543
Key Variants: -156C>A (g.61,881 C>A on AF280107 )


13. CYP3A4*1N

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1N
Haplotype Summary: The defining mutation for CYP3A4*1N is 14200T>G (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in intron 5 of the CYP3A4 gene. This allele was first identified by Dai et al. [PMID: 11714865]. It was found by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects at a frequency of 0.001 [PMID: 14695543].
Key PubMed IDs: 11714865 ,14695543
Key Variants: 14200T>G (g.76,236 T>G on AF280107 )


14. CYP3A4*1P

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1P
Haplotype Summary: The defining mutation for CYP3A4*1P is 15727G>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in intron 7 of the CYP3A4 gene. This allele was first identified by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects with a frequency of 0.001 [PMID: 14695543].
Key PubMed IDs: 14695543
Key Variants : 15727G>A (g.77,763 G>A on AF280107 )


15. CYP3A4*1Q

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1Q
Haplotype Summary: The defining mutation for CYP3A4*1Q is 15809T>C (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in intron 7 of the CYP3A4 gene. This allele was first identified by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects with a frequency of 0.001 [PMID: 14695543].
Key PubMed IDs: 14695543
Key Variants: 15809T>C (g.77,845 T>C on AF280107 )


16. CYP3A4*1R

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1R
Haplotype Summary: The defining mutation for CYP3A4*1R is 16775A>G (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee) . This variant is located in intron 7 of the CYP3A4 gene. This allele was first identified by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects with a frequency of 0.001 [PMID: 14695543].
Key PubMed IDs: 14695543
Key Variants: 16775A>G (g.78,811 A>G on AF280107 )


17. CYP3A4*1S

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1S
Haplotype Summary: The defining mutation for CYP3A4*1S is 17815_17816delAT deletion (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in intron 9 of the CYP3A4 gene. This allele was first identified by Dai et al. [PMID: 11714865]. It was found by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects with a frequency of 0.001 [PMID: 14695543].
Key PubMed IDs: 14695543, 11714865
Key Variants: 17815_17816delAT (g.79,851_79,852delAT on AF280107 )


18. CYP3A4*1T

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*1T
Haplotype Summary: The defining mutation for CYP3A4*1T is 26013T>C (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in 3-prime UTR of the CYP3A4 gene. This allele was first identified by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects with a frequency of 0.001 [PMID: 14695543].
Key PubMed IDs: 14695543
Key Variants: 26013T>C (g.88,049 T>C on AF280107 )


19. CYP3A4*2

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*2
Haplotype Summary: The defining polymorphism for CYP3A4*2 is 15713T>C (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in exon 7 of the CYP3A4 gene and results in a Ser222Pro alteration. This allele was identified by Sata et al. in a White population from Finland with a frequency of 0.027 and was absent in the black and Chinese (Asian) subjects analyzed [PMID: 10668853]. Later Cavaco et al. reported a frequency of 0.045 in Portuguese Caucasians (White) [PMID: 14580164]. Baculovirus-directed cDNA expression revealed that the CYP3A4*2 had a lower intrinsic clearance for the CYP3A4 substrate nifedipine compared with the wild-type enzyme [PMID: 10668853].
Key PubMed IDs: 10668853,14580164
Key Variants: 15713T>C (S222P) (g.77,749 T>C on AF280107 )


20. CYP3A4*3

Gene HGNC
Name: 		CYP3A4
Haplotype
Name: 		CYP3A4*3
Haplotype
Summary: 		This allele was described by Sata et al. [PMID: 10668853 ] as one of the first missense polymorphisms in CYP3A4. Later it was found to have a frequency of 1.1% in Caucasians. [PMID:11375299].
Key PubMed
IDs: 		14580164 , 10668853 ,11375299
Key Variants: 23171T>C (M445T) (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee )
(g.24,592,800 on NT_007933 )


21. CYP3A4*4

Gene HGNC
 Name: 		CYP3A4
Haplotype
Name: 		CYP3A4*4
Haplotype
Summary: 		This allele was first noted by Hsieh et al. in 3/102 Chinese(Asian) subjects. Their study suggested that this allele may result in decreased activity in Chinese [PMID: 11181494].
Key PubMed
IDs: 		11181494
Key Variants: 13871A>G (I118V) (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee )
(g.75,907 A>G on AF280107 )


22. CYP3A4*5

Gene HGNC
Name: 		CYP3A4
Haplotype
Name: 		CYP3A4*5
Haplotype
Summary: 		This allele was first noted by Hsieh et al. in 2/102 Chinese (Asian) subjects. Their study suggested that this allele may result in decreased activity in Chinese [PMID: 11181494].
Key PubMed
IDs: 		11181494
Key Variants: 15702C>G (P218R) (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee )
(g.77,738 C>G on AF280107 )


23. CYP3A4*6

Gene HGNC
Name: 		CYP3A4
Haplotype
Name: 		CYP3A4*6
Haplotype
Summary: 		This allele was first noted by Hsieh et al. in 1/102 Chinese (Asian) subjects. This study suggested that this allele may result in decreased activity in Chinese [PMID: 11181494].
Key PubMed
IDs: 		11181494
Key Variants: 17661_17662insA
(nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee )
(g.79,697insA on AF280107 )


24. CYP3A4*7

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*7
Haplotype Summary: The defining polymorphism for CYP3A4*7 is 6004G>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in exon 3 of the CYP3A4 gene and results in a Gly56Asp alteration. This allele was identified by Eiselt et al. in Caucasians (Whites) from Germany or Switzerland with a frequency of 0.0141 [PMID: 11470997] and in their study did not display significant change from wild-type in terms of in vitro expression or testosterone metabolism.
Key PubMed IDs: 11470997
Key Variants: 6004G>A (G56D) (g.68,040 G>A on AF280107 )


25. CYP3A4*8

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*8
Haplotype Summary: CYP3A4*8: The defining mutation for CYP3A4*8 is 13908G>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ) . This variant is located in exon 5 of the CYP3A4 gene and results in an Arg130Gln alteration. This allele was identified by Eiselt et al. in Caucasians(White) from Germany or Switzerland with a frequency of 0.0033 [PMID: 11470997] , and in their hands, this variation resulted in a lack of detectable P450 holoprotein in vitro.
Key PubMed IDs: 11470997
Key Variants: 13908G>A (R130Q) (g.75,944 G>A on AF280107 )


26. CYP3A4*9

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*9
Haplotype Summary: The defining mutation for CYP3A4*9 is 14292G>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). This variant is located in exon 6 of the CYP3A4 gene and results in a Val170Ile alteration. This allele was identified by Eiselt et al. in Caucasians (White) from Germany or Switzerland with a frequency of 0.0024 [PMID: 11470997] and in their study did not display significant change from wild-type in terms of in vitro expression or testosterone metabolism.
Key PubMed IDs: 11470997
Key Variants: 14292G>A (V170I) (g.76,328 G>A on AF280107 )


27. CYP3A4*10

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*10
Haplotype Summary: The defining mutation for CYP3A4*10 is 14304G>C (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). This variant is located in exon 6 of the CYP3A4 gene and results in an Asp174His alteration. This allele was identified by Eiselt et al. in Caucasians (White) from Germany or Switzerland with a frequency of 0.0024 [PMID: 11470997] and in their study did not display significant change from wild-type in terms of in vitro expression or testosterone metabolism.

 Lamba et al. later reported an allele frequency of 0.02 in "African-Americans" (Black or African American), 0.02 in Caucasians (White) and 0.05 among Mexicans (White, Hispanic or Latino) [PMID: 11875366].
Key PubMed IDs: 11470997, 11875366
Key Variants: 14304G>C (D174H) (g. 76,340 G>C on AF280107 )


28. CYP3A4*11

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*11
Haplotype Summary: The defining mutation for CYP3A4*11 is 21867C>T (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). This variant is located in exon 11 of the CYP3A4 gene and results in a Thr363Met alteration. This allele was identified by Eiselt et al. in Caucasians (White) from Germany or Switzerland with a frequency of 0.0034 [PMID: 11470997]. In vitro, Thr363Met was expressed at significantly lower levels than wild-type CYP3A4 [PMID: 11470997].
Key PubMed IDs: 11470997
Key Variants: 21867C>T (T363M) (g.83,903 C>T on AF280107 )


29. CYP3A4*12

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*12
Haplotype Summary: The defining mutation for CYP3A4*12 is 21896C>T (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). This variant is located in exon 11 of the CYP3A4 gene and results in a Leu373Phe alteration. This allele was identified by Eiselt et al. in Caucasians (White) from Germany or Switzerland with a frequency of 0.0034; it was also shown to have altered midazolam hydroxylation kinetics in vitro [PMID: 11470997].
Key PubMed IDs: 11470997
Key Variants: 21896C>T (L373F) (g.83,932 C>T on AF280107 )


30. CYP3A4*13

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*13
Haplotype Summary: The defining mutation for CYP3A4*13 is 22026C>T (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). This variant is located in exon 11 of the CYP3A4 gene and results in a Pro416Leu alteration. This allele was identified by Eiselt et al. in Caucasians (White) from Germany or Switzerland with a frequency of 0.0034; In vitro, this allele did not result in detectable P450 holoprotein [PMID: 11470997].
Key PubMed IDs: 11470997
Key Variants: 22026C>T (P416L) (g.84,062 C>T on AF280107 )


31. CYP3A4*14

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*14
Haplotype Summary: The defining mutation for CYP3A4*14 is 44T>C (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). This variant is located in exon 1 of the CYP3A4 gene and results in a Leu15Pro alteration. This rare allele was identified by Lamba et al. [PMID: 11875366] in just one individual, and was not observed in any of the other 183 subjects sequenced at the same time.
Key PubMed IDs: 11875366
Key Variants: 44T>C (L15P) (g.62,080 T>C on AF280107 )


32. CYP3A4*15A

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*15A
Haplotype Summary: The defining polymorphism for CYP3A4*15A is 14269G>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). This variant is located in exon 6 of the CYP3A4 gene and results in an Arg162Gln alteration. Lamba et al. reported that three members of an African-American (Black or African American) family of five containing a nifedipine poor metabolizer, including the poor metabolizer, were heterozygous for this allele. It was present in other African-Americans (Black or African American) with a frequency of 0.02 [PMID: 11875366]. Dai et al. reported an allele frequency of 0.04 in Black populations [PMID: 11714865].
Key PubMed IDs: 11714865,11875366
Key Variants: 14269G>A (R162Q) (g.76,305 G>A on AF280107 )


33. CYP3A4*15B

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*15B
Haplotype Summary: The defining polymorphisms for CYP3A4*15B are 14269G>A, -844_-845insATGGAGTGA and -392A>G (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). This allele was identified by Hamzeiy et al. [PMID: 11890939].
Key PubMed IDs: 11890939
Key Variants: 14269G>A (R162Q) (g.76,305 G>A on AF280107 ),
-844_-845insATGGAGTGA (g.61,192insATGGAGTGA on AF280107 ) and
-392A>G (g.61,645 A>G on AF280107 )


34. CYP3A4*16A

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*16A
Haplotype Summary: The defining polymorphism for CYP3A4*16A is 15603C>G (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). This variant is located in exon 7 of the CYP3A4 gene and results in a Thr185Ser alteration. This allele was identified by Lamba et al. This allele was present only in Japanese (Asian) and Mexicans (White, Hispanic or Latino) with a frequency of 0.05, and all these subjects were heterozygous for this SNP [PMID: 11875366].
Key PubMed IDs: 11875366
Key Variants: 15603C>G (T185S) (g.77,639C>G on AF280107 )


35. CYP3A4*16B

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*16B
Haplotype Summary: The defining polymorphisms for CYP3A4*16B are 15603C>G and 20230G>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). The 15603C>G variant is located in exon 7 and results in a Thr185Ser alteration. The 20230G>A variant is located in intron 10. This polymorphism was first identified by Dai et al. [PMID: 11714865]. The *16B allele was found by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects to occur with a frequency of 0.014 [PMID: 14695543]. An alteration of CYP3A4 paclitaxel metabolite levels in vivo has been found in *16B/*1 Japanese (Asian) cancer patients undergoing chemotherapy, and this was inferred to be attributable to the 15603C>G polymorphism [PMID: 16890579].
Key PubMed IDs: 14695543, 11714865, 16890579
Key Variants: 15603C>G (T185S) (g.77,639 C>G on AF280107) and 20230G>A (g.82,266 G>A on AF280107 )


36. CYP3A4*17

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*17
Haplotype Summary: The defining polymorphism for CYP3A4*17 is 15615T>C (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). This variant is located in exon 7 of the CYP3A4 gene and results in a Phe189Ser alteration. This allele was identified by Dai et al. in Caucasians (Whites) with a frequency of 0.02. CYP3A4*17 exhibited lower turnover numbers than wild-type for testosterone and chlorpyrifos in vitro [PMID: 11714865]. In another in vitro study, recombinant CYP3A4*17 was shown to be defective in metabolizing the hypertensive drug nifedipine [PMID: 15634941] , demonstrating a >99% decrease in Vmax and CLmax as compared to wild-type.
Key PubMed IDs: 11714865,15634941
Key Variants: 15615T>C (F189S) (g.77,651 T>C on AF280107 )


37. CYP3A4*18A

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*18A
Haplotype Summary: The defining polymorphism for CYP3A4*18A is 20070T>C (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). This variant is located in exon 10 of the CYP3A4 gene and results in a Leu293Pro alteration. This allele was identified by Dai et al. in Asians with a frequency of 0.02 (occurred in Chinese with a frequency of 0.1) [PMID: 11714865]. They also observed that, in vitro, CYP3A4 L293P had higher turnover numbers for testosterone and chlorpyrifos. It was later reported that this allele in recombinant form does not significantly affect the metabolism of nifedipine in vitro [PMID: 15634941].
Key PubMed IDs: 11714865,15634941
Key Variants: 20070T>C (g.82,106 T>C on AF280107 )


38. CYP3A4*18B

Gene HGNC Name: CYP3A4
Haplotype Name CYP3A4*18B
Haplotype Summary: The defining polymorphisms for CYP3A4*18B are 20070T>C and 20230G>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). The 20070T>C variant, found by Dai et al. [PMID: 11714865 ] is located in exon 10 of the CYP3A4 gene and results in a Leu293Pro alteration. The 20230G>A variant also was first identified by Dai et al. [PMID: 11714865] and is located in intron 10. The *18B haplotype was identified by Fukushima-Uesaka et al. in a Japanese (Asian) population of 416 subjects, in which it occured with a frequency of 0.028 [PMID: 14695543].
Key PubMed IDs: 14695543, 11714865
Key Variants: 20070T>C (g.82,106 T>C on AF280107 ) (L293P) and 20230G>A (g.82,266 G>A on AF280107 )


39. CYP3A4*19

Gene HGNC Name: CYP3A4
Haplotype
Name 		CYP3A4*19
Haplotype Summary: The defining polymorphisms for CYP3A4*19 are 23237C>T and 20230G>A (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee ). Both were identified by Dai et al. [PMID: 11714865]. The 23237C>T variant is located in exon 12 of the CYP3A4 gene, results in a Pro467Ser alteration and was found in Asian subjects with a frequency of 0.02 (it occurred in Indo-Pakistani with a frequency of 0.125). The 20230G>A variant is located in intron 10.
In vitro, the turnover numbers of the CYP3A4*19 for testosterone and chlorpyrifos are not significantly different from those of wild-type CYP3A4 [PMID: 11714865]. It also has been reported that this allele does not significantly affect the metabolism of nifedipine [PMID: 15634941].
Key PubMed
IDs: 		11714865,15634941
Key Variants: 23237C>T (P467S) (g.85,273 C>T on AF280107 )and 20230G>A (g.82,266 on AF280107 )


40. CYP3A4*20

Gene HGNC Name: CYP3A4
Haplotype Name: CYP3A4*20
Haplotype Summary: This haplotype contains a rare variant allele in which a premature stop codon leads to a truncated protein with no function. The heterozygous carrier identified had an intermediate phenotype for midazolam clearance in vivo [ PMID: 16580902].
Key PubMed IDs: 16580902
Key Variants: 25889_25890insA (nomenclature is according to the Human Cytochrome P450 Allele Nomenclature Committee )
(g.87925insA on AF280107)
The PGRN is financially supported by grants from NIGMS, NHLBI, NHGRI, NIEHS, NCI, and NLM within the NIH, HHS. PharmGKB is managed at Stanford University. This work is supported by the NIH/NIGMS Pharmacogenetics Research Network and Database (U01GM61374). ©2001-2008 PharmGKB.