Important Splice Variant Information for CYP3A5
Submitted by: Jatinder Lamba, Erin Schuetz (PAAR)
Reviewed by: Reviewed
Submitted date: February 16, 2006
| Gene HGNC Name: | CYP3A5 |
|---|---|
| Linked to Variant? | CYP3A5*3, CYP3A5*6 |
| Splice Variant Summary: | Figure (adapted from PMID: 11279519 ) shows alternative splicing of CYP3A5*3. SV1 mRNA contains exon 3B (AF355804) , SV2 mRNA contains exons 3B and 4B (AF355801) and SV3 mRNA contains exons 3B, 4B and 5B (AF355802) and is missing exon 6. Presence of these variants targets the aberrantly spliced transcript for nonsense mediated decay [PMID: 15955870 ].  |
| Definitive Publication or Website for this splice variation: | PMID: 11279519 http://www.cypalleles.ki.se/cyp3a5.htm |
| Phenotype Data sets: | Since CYP3A5*3 and CYP3A5*6 variants are associated with generation of splice variants the following phenotype data sets for the CYP3A5 variants are also relevant for splice variants. Phenotype data sets PA130713012 [PMID: 11279519] and PA130713029 [PMID: 12065767] demonstrate association of CYP3A5 variants with CYP3A activity measured as MDZ hydroxylation and CYP3A5 expression measured as mRNA or protein in liver and intestine. Phenotype data sets PA130756033 [PMID: 12694072], PA132837944 [PMID: 14747421] and PA133888800 demonstrate that CYP3A5 expressor genotypes (CYP3A5*1/*1 and *1/*3) require larger tacrolimus dosing than CYP3A5 nonexpressors (CYP3A5*3/*3) in pediatric heart transplant and adult lung transplant patients, respectively. Phenotype data set PA646601 [PMID: 12439220 ] demonstrates that CYP3A5 *3 is not associated with risk of t-ML in children treated for ALL. Phenotype data set PA130713028 [PMID: 12202670 ] explains interindividual differences of docetaxel PK and PD in the Asian population are associated with CYP3A5 genotype. CYP3A5*3 allele frequency in various populations is significantly correlated with their distance from equator [PMID: 15492926]. Other data sets of interest that demonstrate that CYP3A5 genotype is associated with drug metabolism and clearance: tacrolimus (PA133888947), etoposide (PA132837945), docetaxel and midazolam (PA129966512), midazolam (PA129411304), irinotecan (PA130150454, PA130713026 [PMID: 12960109], PA129966511, PA130150455). |