CYP2D6
protein-codingcytochrome P450 family 2 subfamily D member 6, the group of Cytochrome P450 family 2
Gene summary
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize as many as 25% of commonly prescribed drugs. Its substrates include antidepressants, antipsychotics, analgesics and antitussives, beta adrenergic blocking agents, antiarrythmics and antiemetics. The gene is highly polymorphic in the human population; certain alleles result in the poor metabolizer phenotype, characterized by a decreased ability to metabolize the enzyme's substrates. Some individuals with the poor metabolizer phenotype have no functional protein since they carry 2 null alleles whereas in other individuals the gene is absent. This gene can vary in copy number and individuals with the ultrarapid metabolizer phenotype can have 3 or more active copies of the gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]
- CYP2DL1
- CYP2D7P2
- CYP2D7BP
- CYP2D8P2
- CYP2D7AP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: Pharmacogenomic
Rationale: Variants may affect the metabolism of mulitple drugs including debrosoquine, sparteine, nortriptyline, codeine, tamoxifen
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CYP2D6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000106.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 13 | 9 | 22 | |||
| missense | 98 | 14 | 112 | |||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 1 | 4 | 5 | |||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 3 | |||
| Total | 0 | 0 | 115 | 29 | 0 | 144 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000097.3 | 9 | MANE Select | |
| Ensembl | ENSP00000496150.1 | 9 | MANE Select | |
| RefSeq | NP_001020332.2 | 8 | Standard | |
| Ensembl | ENSP00000351927.4 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Citalopram Pathway, Pharmacokinetics
- Celecoxib Pathway, Pharmacokinetics
- Benzodiazepine Pathway, Pharmacokinetics
- Serotonergic synapse - Homo sapiens (human)
- Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)
Biological Process
- organic acid metabolic process
- xenobiotic metabolic process
- steroid metabolic process
- coumarin metabolic process
- alkaloid metabolic process
Molecular Function
- monooxygenase activity
- iron ion binding
- drug binding
- steroid hydroxylase activity
- oxidoreductase activity
Cellular Component
- cytoplasm
- mitochondrion
- endoplasmic reticulum
- endoplasmic reticulum membrane
- organelle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000360608
- Coding exons
- 9
- Length
- 4408
- Individuals with no LoFs
- 120562
- Homozygous LoFs
- 166
- Heterozygous LoFs
- 4989
- Defined
- 125717
- p
- 0.0207
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -2.00 | 403 | 305 | 1.32 | 0.0000219 | 3074 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.011 | 0.0096 | notable |
| Latino/Admixed American | 0.0095 | 0.0091 | notable |
| Ashkenazi Jewish | 0.013 | 0.013 | notable |
| East Asian | 0.0030 | 0.0028 | notable |
| Finnish | 0.057 | 0.056 | notable |
| European (Non-Finnish) | 0.029 | 0.027 | notable |
| South Asian | 0.0050 | 0.0048 | notable |
| Other | 0.017 | 0.016 | notable |
dbNSFP Gene Annotations
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}.;
Intolerance Scores
- RVIS EVS
- 1.77
- RVIS percentile EVS
- 96.77
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.149
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |