CYP2D6
Basic information
Region (hg38): 22:42126499-42130865
Previous symbols: [ "CYP2DL1", "CYP2D7P2", "CYP2D7BP", "CYP2D8P2", "CYP2D7AP" ]
Links
Phenotypes
GenCC
Source:
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Drug metabolism, CYP2CD6-related | AD | Pharmacogenomic | Variants may affect the metabolism of mulitple drugs including debrosoquine, sparteine, nortriptyline, codeine, tamoxifen | General | 4082245; 1978251; 1673290; 8093319; 7903454; 9012401; 11940091; 15625333; 19809024 ; 22406651; 22733239; 22775532 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP2D6 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 3 | |||||
missense | 26 | 12 | 39 | |||
nonsense | 1 | |||||
start loss | 0 | |||||
frameshift | 3 | |||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 2 | |||||
splice region | 0 | |||||
non coding | 4 | |||||
Total | 0 | 0 | 26 | 26 | 1 |
Variants in CYP2D6
This is a list of pathogenic ClinVar variants found in the CYP2D6 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
22-42126532-A-G | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126536-T-C | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126597-C-T | not specified | Uncertain significance (Mar 23, 2022) | ||
22-42126611-C-G | not specified | Benign; other (Jan 17, 2024) | ||
22-42126611-C-C | not specified • Tramadol response | Benign/Likely benign (Dec 30, 2023) | ||
22-42126627-A-G | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126667-C-T | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126682-C-G | not specified | Uncertain significance (Dec 19, 2023) | ||
22-42126736-G-A | Likely benign (Dec 01, 2022) | |||
22-42126744-C-T | not specified | Uncertain significance (Jun 22, 2023) | ||
22-42126747-G-A | drug response (-) | |||
22-42126749-C-T | drug response (-) | |||
22-42126753-C-T | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126803-T-C | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126813-C-T | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126819-A-G | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126865-A-T | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126881-T-C | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126925-C-T | not specified | Uncertain significance (Jan 02, 2024) | ||
22-42126931-G-A | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126944-C-T | Tramadol response | drug response (Apr 28, 2018) | ||
22-42126963-C-T | Likely benign (Aug 01, 2024) | |||
22-42127001-G-G | Tramadol response | drug response (Apr 28, 2018) | ||
22-42127027-G-A | Tramadol response | drug response (Apr 28, 2018) | ||
22-42127169-C-T | Tramadol response | drug response (Apr 28, 2018) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
CYP2D6 | protein_coding | protein_coding | ENST00000360608 | 9 | 4408 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.08e-25 | 0.00000257 | 120562 | 166 | 4989 | 125717 | 0.0207 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -2.00 | 403 | 305 | 1.32 | 0.0000219 | 3074 |
Missense in Polyphen | 130 | 101.19 | 1.2847 | 1069 | ||
Synonymous | -3.99 | 200 | 140 | 1.43 | 0.0000108 | 1037 |
Loss of Function | -2.57 | 31 | 18.9 | 1.64 | 0.00000110 | 188 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.0201 | 0.0191 |
Ashkenazi Jewish | 0.0131 | 0.0127 |
East Asian | 0.00298 | 0.00283 |
Finnish | 0.0572 | 0.0559 |
European (Non-Finnish) | 0.0288 | 0.0275 |
Middle Eastern | 0.00298 | 0.00283 |
South Asian | 0.00496 | 0.00478 |
Other | 0.0172 | 0.0164 |
dbNSFP
Source:
- Function
- FUNCTION: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants. {ECO:0000269|PubMed:16352597}.;
- Pathway
- Citalopram Pathway, Pharmacokinetics;Celecoxib Pathway, Pharmacokinetics;Benzodiazepine Pathway, Pharmacokinetics;Serotonergic synapse - Homo sapiens (human);Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Drug metabolism - cytochrome P450 - Homo sapiens (human);Imipramine/Desipramine Pathway, Pharmacokinetics;Imatinib Pathway, Pharmacokinetics/Pharmacodynamics;Statin Pathway - Generalized, Pharmacokinetics;Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics;Fluvastatin Pathway, Pharmacokinetics;Phenytoin Pathway, Pharmacokinetics;Tamoxifen Pathway, Pharmacokinetics;Codeine and Morphine Pathway, Pharmacokinetics;Gefitinib Pathway, Pharmacokinetics;Fluoxetine Pathway, Pharmacokinetics;Tramadol Pharmacokinetics;Nevirapine Pathway, Pharmacokinetics;Clomipramine Pathway, Pharmacokinetics;Doxepin Pathway, Pharmacokinetics;Pathway_PA165986194 -need delete;Acetaminophen Pathway, Pharmacokinetics;Venlafaxine Pathway, Pharmacokinetics;Fluoxetine Action Pathway;Citalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Celecoxib Action Pathway;Methadone Metabolism Pathway;Imipramine Metabolism Pathway;Desipramine Metabolism Pathway;Citalopram Metabolism Pathway;Codeine Metabolism Pathway;Tamoxifen Action Pathway;Methadone Action Pathway;Codeine Action Pathway;Tramadol Metabolism Pathway;Venlafaxine Metabolism Pathway;Clomipramine Metabolism Pathway;Acetaminophen Metabolism Pathway;Doxepin Metabolism Pathway;Fluoxetine Metabolism Pathway;Celecoxib Metabolism Pathway;Nevirapine Metabolism Pathway;Tamoxifen Metabolism Pathway;Codeine and Morphine Metabolism;Fatty Acid Omega Oxidation;Aripiprazole Metabolic Pathway;Vitamin D Receptor Pathway;Melatonin metabolism and effects;Oxidation by Cytochrome P450;Tamoxifen metabolism;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Xenobiotics;Tyrosine metabolism;Fatty acids;Androgen and estrogen biosynthesis and metabolism;Miscellaneous substrates;Cytochrome P450 - arranged by substrate type;Leukotriene metabolism;Biological oxidations;Metabolism;Biosynthesis of maresin-like SPMs;Biosynthesis of maresins;Biosynthesis of DHA-derived SPMs;Biosynthesis of specialized proresolving mediators (SPMs);Fatty acid metabolism;Linoleate metabolism;C21-steroid hormone biosynthesis and metabolism;Xenobiotics metabolism;Tryptophan degradation;CYP2E1 reactions;Arachidonic acid metabolism
(Consensus)
Intolerance Scores
- loftool
- rvis_EVS
- 1.77
- rvis_percentile_EVS
- 96.77
Haploinsufficiency Scores
- pHI
- hipred
- N
- hipred_score
- 0.146
- ghis
- 0.437
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.149
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | High |
Cancer | Medium | Medium | Medium |
Gene ontology
- Biological process
- organic acid metabolic process;xenobiotic metabolic process;steroid metabolic process;coumarin metabolic process;alkaloid metabolic process;alkaloid catabolic process;monoterpenoid metabolic process;drug metabolic process;arachidonic acid metabolic process;isoquinoline alkaloid metabolic process;drug catabolic process;exogenous drug catabolic process;long-chain fatty acid biosynthetic process;heterocycle metabolic process;negative regulation of binding;oxidation-reduction process;oxidative demethylation;negative regulation of cellular organofluorine metabolic process
- Cellular component
- cytoplasm;mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;organelle membrane;intracellular membrane-bounded organelle
- Molecular function
- monooxygenase activity;iron ion binding;drug binding;steroid hydroxylase activity;oxidoreductase activity;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen;heme binding;aromatase activity