CYP2C8

cytochrome P450 family 2 subfamily C member 8, the group of Cytochrome P450 family 2

Basic information

Region (hg38): 10:95036771-95069497

Links

ENSG00000138115 ∙ NCBI:1558 ∙ OMIM:601129 ∙ HGNC:2622 ∙ Uniprot:P10632 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the CYP2C8 gene.

• Inborn genetic diseases (11 variants)
• not provided (6 variants)
• not specified (1 variants)
• - (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.

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	1	4
missense			10	2	1	13
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	10	5	3

Variants in CYP2C8

This is a list of pathogenic ClinVar variants found in the CYP2C8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-95037285-C-T		not specified	Uncertain significance (Jan 17, 2024)
10-95037713-C-T		Pulmonary disease, chronic obstructive, susceptibility to	association (Jul 05, 2022)
10-95038960-C-A		not specified	Uncertain significance (Sep 20, 2023)
10-95038964-G-T		not specified	Uncertain significance (Jan 30, 2024)
10-95038992-T-C		Pulmonary disease, chronic obstructive, susceptibility to • CYP2C8-related disorder	Benign (Oct 29, 2019)
10-95039038-C-T			Likely benign (Jul 17, 2018)
10-95042946-C-T		CYP2C8-related disorder	Likely benign (Oct 04, 2019)
10-95042980-G-A			Benign (Nov 16, 2018)
10-95042997-T-C		not specified	Uncertain significance (Dec 20, 2023)
10-95043013-C-T			Likely benign (Jul 20, 2018)
10-95045837-G-T		not specified	Uncertain significance (Jul 19, 2023)
10-95045840-G-C		not specified	Uncertain significance (Aug 08, 2022)
10-95058349-T-A		CYP2C8 POLYMORPHISM	Benign (Jun 20, 2018)
10-95058362-G-C		CYP2C8 POLYMORPHISM • CYP2C8-related disorder	Benign (Feb 07, 2020)
10-95058391-G-C		not specified	Uncertain significance (Oct 13, 2023)
10-95058397-C-G		not specified	Uncertain significance (Jan 17, 2024)
10-95058400-G-C		not specified	Uncertain significance (Jun 28, 2023)
10-95058401-G-T		not specified	Uncertain significance (Oct 26, 2021)
10-95058412-C-T		not specified	Likely benign (Oct 26, 2022)
10-95064828-A-C		not specified	Uncertain significance (Apr 12, 2022)
10-95064833-T-G		not specified	Uncertain significance (Jul 09, 2021)
10-95064897-A-G		not specified	Uncertain significance (Mar 07, 2024)
10-95064901-C-T		CYP2C8-related disorder	Benign (Nov 10, 2020)
10-95064922-G-A		not specified	Uncertain significance (Oct 13, 2021)
10-95064934-G-A			Likely benign (Jun 01, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

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