CYP2C8
cytochrome P450 family 2 subfamily C member 8, the group of Cytochrome P450 family 2
Basic information
Region (hg38): 10:95036772-95069497
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Drug metabolism, CYP2C8-related | AD/AR | Pharmacogenomic | 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 | General | 15365880; 28378927 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (46 variants)
- not_provided (8 variants)
- CYP2C8-related_disorder (5 variants)
- DRUG_METABOLISM,_ALTERED,_CYP2C8-RELATED (1 variants)
- CYP2C8_POLYMORPHISM (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP2C8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000770.3. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | |||||
| missense | 44 | 51 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 0 | 44 | 9 | 4 |
Highest pathogenic variant AF is 0.00006939075
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CYP2C8 | protein_coding | protein_coding | ENST00000371270 | 9 | 32725 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.98e-22 | 0.0000301 | 125463 | 0 | 285 | 125748 | 0.00113 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.887 | 299 | 259 | 1.16 | 0.0000128 | 3247 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00306 | 0.00305 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.00647 | 0.00644 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000651 | 0.000651 |
| Middle Eastern | 0.00647 | 0.00644 |
| South Asian | 0.000588 | 0.000588 |
| Other | 0.000979 | 0.000978 |
dbNSFP
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}.;
- Pathway
- Amodiaquine Pathway, Pharmacokinetics;Rosiglitazone Pharmacokinetic Pathway;Retinol metabolism - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Drug metabolism - cytochrome P450 - Homo sapiens (human);Arachidonic acid metabolism - Homo sapiens (human);Linoleic acid metabolism - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Carbamazepine Pathway, Pharmacokinetics;Statin Pathway - Generalized, Pharmacokinetics;Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics;Fluvastatin Pathway, Pharmacokinetics;Warfarin Pathway, Pharmacokinetics;Phenytoin Pathway, Pharmacokinetics;Anti-diabetic Drug Repaglinide Pathway, Pharmacokinetics;Taxane Pathway, Pharmacokinetics;Erlotinib Pathway, Pharmacokinetics;Caffeine Pathway, Pharmacokinetics;Sorafenib Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics;Ibuprofen Pathway, Pharmacokinetics;Cyclophosphamide Pathway, Pharmacokinetics;Ifosfamide Pathway, Pharmacokinetics;Etodolac Action Pathway;Ketoprofen Action Pathway;Ibuprofen Action Pathway;Rofecoxib Action Pathway;Acetylsalicylic Acid Action Pathway;Diflunisal Action Pathway;Rosiglitazone Metabolism Pathway;Mycophenolic Acid Metabolism Pathway;Leukotriene C4 Synthesis Deficiency;Ibuprofen Metabolism Pathway;Acetaminophen Action Pathway;Celecoxib Action Pathway;Sulindac Action Pathway;Diclofenac Action Pathway;Ketorolac Action Pathway;Methadone Metabolism Pathway;Naproxen Action Pathway;Etoricoxib Action Pathway;Carprofen Action Pathway;Flurbiprofen Action Pathway;Fenoprofen Action Pathway;Antrafenine Action Pathway;Antipyrine Action Pathway;Lumiracoxib Action Pathway;Magnesium salicylate Action Pathway;Methadone Action Pathway;Trisalicylate-choline Action Pathway;Nepafenac Action Pathway;Phenylbutazone Action Pathway;Lornoxicam Action Pathway;Salsalate Action Pathway;Tenoxicam Action Pathway;Tiaprofenic Acid Action Pathway;Tolmetin Action Pathway;Salicylic Acid Action Pathway;Salicylate-sodium Action Pathway;Carbamazepine Metabolism Pathway;Cyclophosphamide Action Pathway;Ifosfamide Action Pathway;Sorafenib Metabolism Pathway;Oxaprozin Action Pathway;Valdecoxib Action Pathway;Nabumetone Action Pathway;Caffeine Metabolism;Cyclophosphamide Metabolism Pathway;Ifosfamide Metabolism Pathway;Indomethacin Action Pathway;Meloxicam Action Pathway;Suprofen Action Pathway;Bromfenac Action Pathway;Mefenamic Acid Action Pathway;Arachidonic Acid Metabolism;Piroxicam Action Pathway;Codeine and Morphine Metabolism;VEGFA-VEGFR2 Signaling Pathway;Oxidation by Cytochrome P450;Arachidonate Epoxygenase - Epoxide Hydrolase;Tamoxifen metabolism;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE);Arachidonic acid metabolism;Xenobiotics;Tyrosine metabolism;Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET);Androgen and estrogen biosynthesis and metabolism;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)
Recessive Scores
- pRec
- 0.233
Intolerance Scores
- loftool
- 0.924
- rvis_EVS
- 0.44
- rvis_percentile_EVS
- 77.91
Haploinsufficiency Scores
- pHI
- 0.0449
- hipred
- N
- hipred_score
- 0.112
- ghis
- 0.384
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.300
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cyp2c39
- Phenotype
Gene ontology
- Biological process
- lipid hydroxylation;organic acid metabolic process;xenobiotic metabolic process;steroid metabolic process;drug metabolic process;epoxygenase P450 pathway;exogenous drug catabolic process;long-chain fatty acid biosynthetic process;oxidation-reduction process;oxidative demethylation;omega-hydroxylase P450 pathway
- Cellular component
- cytoplasm;endoplasmic reticulum membrane;organelle membrane;intracellular membrane-bounded organelle
- 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;heme binding;caffeine oxidase activity;aromatase activity;estrogen 16-alpha-hydroxylase activity