VIP Variant in CYP2D6
The deletion of amino acid K281 can be caused either by CYP2D6 2613-2615 del AGA or _CYP2D_6 2615-2617 del AAG [Articles:1844820, 2574001]. In vitro work on this mutation in HepG2 cells indicated that this variant exhibited reduced function, although without changing the Km of bufuralol, debrisoquine, or sparteine, which suggests that the expression level of the protein may be altered by this mutation. CYP2D6 2613-2615 del AGA is the definitive variation for the CYP2D6*9 haplotype [Article:10634130]. Further in vivo work with this polymorphism has cast doubt on whether or not it leads to reduced function [Article:8101460].
Note: The CYP2D6 gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand, therefore the alleles within our variant annotations will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.
Appendix
CYP2D6: 2613-2615 del AGA or 2615-2617 del AAG
| Genomic Variant & GenBank ID: | 4232-4234 del AGA on M33388 or 4234-4236 del AAG on M33388 |
|---|---|
| mRNA Variant & GenBank ID: | 839-841 del AGA on X08006 or 841-843 del AAG on X08006 |
| Protein Variant & GenBank ID: | deletes K281 on AAH75024 |
| GoldenPath Position: | chr22:40854122-40854124 or chr22:40854120-40854122 on hg 18 |
Connected Drugs
Connected Diseases
| Evidence | Disease |
|---|---|
| Cystic Fibrosis | |
| Depression | |
| Hypertension | |
| Neoplasms | |
| Pain | |
| Parkinson Disease | |
| Schizophrenia |
Publications related to rs5030656 at chr22:42524176: 3
| Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data. Pharmacogenetics. 1999. Gaedigk A, et al. [Article:10634130@PubMed] | |
| Debrisoquine oxidation polymorphism: phenotypic consequences of a 3-base-pair deletion in exon 5 of the CYP2D6 gene. Pharmacogenetics. 1993. Broly F, et al. [Article:8101460@PubMed] | |
| Identification of a new variant CYP2D6 allele lacking the codon encoding Lys-281: possible association with the poor metabolizer phenotype. Pharmacogenetics. 1991. Tyndale R, et al. [Article:1844820@PubMed] |
Cross-References
- UCSC Golden Path:
- chr22:42524176
- dbSNP:
- rs5030656
- ALFRED:
- SI015496Z