CYP2C8
protein-codingcytochrome P450 family 2 subfamily C member 8, 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 its expression is induced by phenobarbital. The enzyme is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, benzo(a)pyrene, 7-ethyoxycoumarin, and the anti-cancer drug taxol. This gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.7 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: Selection and dosing of medications may be affected by the presence of variants; An individual with homozygosity for a frameshift variant developed acute rhabdomyolysis after cervistatin treatment; Patients with homozygous/compound heterozygous variant may be at risk for complications from medications including statins
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CYP2C8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000770.3. 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 | 1 | 4 | 2 | 7 | ||
| missense | 51 | 5 | 2 | 58 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 0 | 52 | 9 | 4 | 66 |
Highest pathogenic variant AF is 0.00006939075
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000761.3 | 9 | MANE Select | |
| Ensembl | ENSP00000360317.3 | 9 | MANE Select | |
| RefSeq | NP_001185782.1 | 8 | Standard | |
| RefSeq | NP_001185783.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Amodiaquine Pathway, Pharmacokinetics
- Rosiglitazone Pharmacokinetic Pathway
- Retinol metabolism - Homo sapiens (human)
- Serotonergic synapse - Homo sapiens (human)
- Drug metabolism - cytochrome P450 - Homo sapiens (human)
Biological Process
- lipid hydroxylation
- organic acid metabolic process
- xenobiotic metabolic process
- steroid metabolic process
- drug metabolic process
Molecular Function
- monooxygenase activity
- iron ion binding
- arachidonic acid epoxygenase activity
- steroid hydroxylase 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
Cellular Component
- cytoplasm
- endoplasmic reticulum membrane
- organelle membrane
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371270
- Coding exons
- 9
- Length
- 32725
- Individuals with no LoFs
- 125463
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 285
- Defined
- 125748
- p
- 0.00113
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.887 | 299 | 259 | 1.16 | 0.0000128 | 3247 |
| Missense (PolyPhen) | 103 | 82.202 | 1.253 | 1079 | ||
| Synonymous | 0.193 | 91 | 93.4 | 0.975 | 0.00000447 | 938 |
| Loss of Function | -1.85 | 28 | 19.2 | 1.46 | 0.00000101 | 233 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0022 | 0.0022 | notable |
| Latino/Admixed American | 0.00090 | 0.00090 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.0065 | 0.0064 | notable |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00065 | 0.00065 | rare |
| South Asian | 0.00059 | 0.00059 | rare |
| Other | 0.00098 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol). {ECO:0000269|PubMed:26427316, ECO:0000269|PubMed:7574697}.;
Recessive Scores
- pRec
- 0.233
Intolerance Scores
- LoFtool
- 0.924
- RVIS EVS
- 0.44
- RVIS percentile EVS
- 77.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.300
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |