CYP2B6

protein-coding

cytochrome P450 family 2 subfamily B member 6, the group of Cytochrome P450 family 2

Gene summary

This gene, CYP2B6, 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 some xenobiotics, such as the anti-cancer drugs cyclophosphamide and ifosphamide. Transcript variants for this gene have been described; however, it has not been resolved whether these transcripts are in fact produced by this gene or by a closely related pseudogene, CYP2B7. Both the gene and the pseudogene are located in the middle of a CYP2A pseudogene found in a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. [provided by RefSeq, Jul 2008]

Previous symbols:

CYP2B

MANE transcript

NM_000767.5

Inheritance

ClinVar variants

U:85B:18

Top phenotype

Efavirenz, poor metabolism of

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr19:40,991,282-41,018,398

External References & Databases

Ensembl (ENSG00000197408)

Transcript & Mutation Effects

hg38 • Region Span ~27.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Efavirenz, poor metabolism ofAD

Manifestation: General

Intervention: Pharmacogenomic

Rationale: It has been suggested that CYP2B6 genotype should be considered in efavirenz treatment

Refs: 15622315; 20639527; 20860463; 23080225; 23152403

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYP2B6 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 77

CYP2B6-related disorderTotal: 14

Efavirenz responseTotal: 7

not providedTotal: 6

nevirapine response - ToxicityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000767.5. 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				10 clinvar		10
missense			82 clinvar	6 clinvar		88
nonsense			2 clinvar			2
start loss						0
frameshift					2 clinvar	2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	85	16	2	103

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000767.5	RefSeq	NP_000758.1	9	MANE Select
ENST00000324071.10	Ensembl	ENSP00000324648.2	9	MANE Select
ENST00000593831.1	Ensembl	ENSP00000470582.1	5	Standard
ENST00000593831.2	Ensembl	ENSP00000470582.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Artemisinin and Derivatives Pathway, Pharmacokinetics
Retinol metabolism - Homo sapiens (human)
Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)
Drug metabolism - cytochrome P450 - Homo sapiens (human)
Arachidonic acid metabolism - Homo sapiens (human)

Biological Process

organic acid metabolic process
xenobiotic metabolic process
steroid metabolic process
drug metabolic process
epoxygenase P450 pathway

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: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000324071
Coding exons: 9
Length: 27100
Individuals with no LoFs: 125354
Homozygous LoFs: 5
Heterozygous LoFs: 389
Defined: 125748
p: 0.00157

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.976	332	286	1.16	0.0000177	3221
Missense (PolyPhen)		100	93.172	1.0733		1180
Synonymous	-1.50	131	111	1.18	0.00000679	984
Loss of Function	0.737	17	20.6	0.825	0.00000135	217

Population LoF Frequency

Population	CAF	p-value	Status
African	0.024	0.013	notable
Latino/Admixed American	0.0015	0.0013	notable
Ashkenazi Jewish	0.0058	0.0058	notable
East Asian	0.00027	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00051	0.00047	rare
South Asian	0.00056	0.00052	rare
Other	0.0023	0.0018	notable

dbNSFP Gene Annotations

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. Acts as a 1,4-cineole 2-exo-monooxygenase. {ECO:0000269|PubMed:11695850, ECO:0000269|PubMed:20061448, ECO:0000269|PubMed:21875942, ECO:0000269|PubMed:22909231}.;

Intolerance Scores

LoFtool: 0.888
RVIS EVS: 2.36
RVIS percentile EVS: 98.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.303

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium