Variant Annotations
PharmGKB variant annotations provide information about variant-drug pairs based on individual PubMed publications. Each annotation represents information from a single paper and the goal is to report the information that the author states, not an interpretation of the paper. The PMID for supporting PubMed publications is found in the "Evidence" field.
Information presented, including study size, allele frequencies and statistics is taken directly from the publication. However, if the author does not correct p-values in cases of multiple hypotheses, curators may apply a Bonferroni correction. Curators attempt to report study size based on the actual number of participants used for the calculation of the association statistics, so the number may vary slightly from what is reported in the abstract of the paper. OMB Race Category information is derived from the paper and mapped to standardized categories. Category definitions may be found by clicking on the "OMB Race Category" link.
There are 2 annotations for this variant. Register or sign in to see them.
VIP Variant in CYP2D6
CYP2D6 100C>T (also seen as 188C>T in the literature) is part of both the non-functional CYP2D6*4 haplotype and the reduced function CYP2D6*10 haplotype. Since CYP2D6 100C>T is present in both a non-functional and a reduced function haplotype, it is not likely to be the causative SNP for the lack of function observed with CYP2D6*4. According to Gaedigk et al [Article:10634130], the presence of CYP2D6 100C>T (188C>T by their nomenclature), and the absence of CYP2D6 1846G>A (1934G>A) is diagnostic of CYP2D6*10.
In vitro studies in both COS-1 [Article:2211621]and V79 [Article:12386125] cells have shown that cells transfected with CYP2D6 100C>T alone exhibit reduced function, suggesting that this mutation contributes to the reduced function of the CYP2D6*10 allele. Association studies have examined the role of this variant in contributing to generalized tonic clonic seizures (GTCS) seen in epilepsy (no association found) [Article:16835697] and tardive dyskinesia in Chinese Schizophrenic patients (weakly positive) [Article:16490169].
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: 100C>T
| Genomic Variant & GenBank ID: | C1719T on M33388 |
|---|---|
| mRNA Variant & GenBank ID: | C100T on X08006 |
| Protein Variant & GenBank ID: | P34S on AAH75024 |
| GoldenPath Position: | chr22:40856638 on hg 18 |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): | GM17201 |
| DNA Source Containing Heterozygous Reference Allele(Coriell Lines): | GM17203 |
| DNA Source Containing Homozygous Minor Allele(Coriell Lines): | GM17225 |
| Key Haplotypes: | CYP2D6*4, CYP2D6*10 |
Connected Drugs
Connected Drug Classes
| Evidence | Drug Class |
|---|---|
| Variant Annotation | antipsychotics |
Connected Diseases
Publications related to rs1065852 at chr22:42526694: 5
Cross-References
- UCSC Golden Path:
- chr22:42526694
- dbSNP:
- rs1065852
- ALFRED:
- SI000466Q
Platform Availability
- Illumina