Tclin CYP2D6 Cytochrome P450 2D6

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• P10635
• Q16752
• Q2XND6
• Q2XND7
• Q2XNE0
• Q6B012
• Q6NXU8

Gene Name

• CYP2D6

Ensembl ID

• ENST00000359033
• ENSP00000351927
• ENSG00000100197
• ENST00000360608
• ENSP00000353820
• ENST00000612990
• ENSP00000483677
• ENSG00000275211
• ENST00000645361
• ENSP00000496150
• ENST00000645508
• ENSP00000496296

Symbol

• CYP2DL1
• CPD6
• CYP2D
• CYP2DL1
• CYPIID6
• P450C2D
• P450DB1
• CYP2D7AP
• CYP2D7BP
• CYP2D7P2
• CYP2D8P2
• P450-DB1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	1
chemical	1
disease	1
drug	1
co-expressed gene	0.98

Related Tools

Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 5035.54   (req: < 5)

Gene RIFs: 545   (req: <= 3)

Antibodies: 570   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 5035.54   (req: >= 5)

Gene RIFs: 545   (req: > 3)

Antibodies: 570   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 26

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 1220

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 58

Approved Drugs (58)

Explore Approved Drugs

1 – 10 of 58

fampridine

CYP2D6Tclin Enzyme

AC50 : 7.2

chlorpromazine

CYP2D6Tclin Enzyme

AC50 : 6.8

clemastine

CYP2D6Tclin Enzyme

AC50 : 6.1

fluphenazine

CYP2D6Tclin Enzyme

AC50 : 6.2

lisuride

CYP2D6Tclin Enzyme

IC50 : 7.8

metergoline

CYP2D6Tclin Enzyme

IC50 : 6.7

prochlorperazine

CYP2D6Tclin Enzyme

IC50 : 6.52

cisapride

CYP2D6Tclin Enzyme

IC50 : 7.16

nortriptyline

CYP2D6Tclin Enzyme

IC50 : 6

spiperone

CYP2D6Tclin Enzyme

AC50 : 6

Active Ligands (1220)

Explore Active Ligands

1 – 10 of 1220

Pipamazine

CYP2D6Tclin Enzyme

IC50 : 7

TG02

CYP2D6Tclin Enzyme

IC50 : 6.02

SP600125

CYP2D6Tclin Enzyme

AC50 : 6.4

NPS 2143

CYP2D6Tclin Enzyme

IC50 : 10.35

CHEMBL486278

CYP2D6Tclin Enzyme

IC50 : 8.9

ibudilast

CYP2D6Tclin Enzyme

AC50 : 7.4

Lysergol

CYP2D6Tclin Enzyme

IC50 : 6

Sulconazole

CYP2D6Tclin Enzyme

IC50 : 6.1

Valethamate Bromide

CYP2D6Tclin Enzyme

IC50 : 6.61

CHEMBL1767164

CYP2D6Tclin Enzyme

IC50 : 7.4

GWAS Traits (12)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
intelligence	EFO_0004337	6	6	2	6.3	84.3
schizophrenia	EFO_0000692	8	4	3	1.1	82.5
self reported educational attainment	EFO_0004784	2	2	2		76.2
cognitive function measurement	EFO_0008354	1	1	1		66.3
mathematical ability	EFO_0004875	2	2	2		63

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
intelligence	EFO_0004337	2	6.3	84.3
schizophrenia	EFO_0000692	3	1.1	82.5
self reported educational attainment	EFO_0004784	2		76.2
cognitive function measurement	EFO_0008354	1		66.3
mathematical ability	EFO_0004875	2		63

Reset Zoom  Beta Count   Odds Ratio

Orthologs (7)

1 – 5 of 7

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cytochrome P450, family 2, subfamily D, polypeptide 6		470228
Macaque	cytochrome P450 2D17-like		100424965
Mouse	cytochrome P450, family 2, subfamily d, polypeptide 22	MGI:1929474	56448
Rat	cytochrome P450, family 2, subfamily d, polypeptide 4	RGD:620640	171522
Horse	cytochrome P450 2D50		100070945

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cytochrome P450, family 2, subfamily D, polypeptide 6
Macaque	cytochrome P450 2D17-like
Mouse	cytochrome P450, family 2, subfamily d, polypeptide 22
Rat	cytochrome P450, family 2, subfamily d, polypeptide 4
Horse	cytochrome P450 2D50

Protein Structure (12 Structures, 1 AlphaFold Model)

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Representation

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Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P10635-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 12

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (26)

Reactome (13)

KEGG (4)

PathwayCommons (1)

WikiPathways (8)

Biological oxidations (R-HSA-211859)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Biological oxidations	221 targets	R-HSA-211859
Reactome	Biosynthesis of DHA-derived SPMs	17 targets	R-HSA-9018677
Reactome	Biosynthesis of maresin-like SPMs	6 targets	R-HSA-9027307
Reactome	Biosynthesis of maresins	8 targets	R-HSA-9018682
Reactome	Biosynthesis of specialized proresolving mediators (SPMs)	19 targets	R-HSA-9018678

Name	Explore in Pharos	Explore in Source
Biological oxidations	221 targets	R-HSA-211859
Biosynthesis of DHA-derived SPMs	17 targets	R-HSA-9018677
Biosynthesis of maresin-like SPMs	6 targets	R-HSA-9027307
Biosynthesis of maresins	8 targets	R-HSA-9018682
Biosynthesis of specialized proresolving mediators (SPMs)	19 targets	R-HSA-9018678

Gene Ontology Terms (32)

Functions (8)

Components (6)

Processes (18)

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10

1 – 8 of 8

GO Term	Evidence	Assigned by
drug binding	Inferred from Direct Assay (IDA)	BHF-UCL
heme binding	Inferred from Direct Assay (IDA)	UniProtKB
monooxygenase activity	Inferred from Direct Assay (IDA)	BHF-UCL
oxidoreductase activity	Inferred from Direct Assay (IDA)	BHF-UCL
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	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
steroid hydroxylase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
aromatase activity	Inferred from Electronic Annotation (IEA)	UniProtKB-EC
iron ion binding	Inferred from Electronic Annotation (IEA)	InterPro

Protein-Protein Interactions (107)

Explore Interacting Targets

1 – 10 of 107

• See Interactions on String-DB

FMO3

Tbio

Family:  Enzyme

Novelty:  0.00567911

Score:  0.961

Data Source:  STRINGDB

FMO1

Tbio

Family:  Enzyme

Novelty:  0.02090294

Score:  0.959

Data Source:  STRINGDB

MAOA

Tclin

Family:  Enzyme

Novelty:  0.00031037

Score:  0.951

Data Source:  STRINGDB

FMO5

Tbio

Family:  Enzyme

Novelty:  0.05610368

Score:  0.948

Data Source:  STRINGDB

CYP3A4

Tclin

Family:  Enzyme

Novelty:  0.00015515

Score:  0.948

Data Source:  STRINGDB

MAOB

Tclin

Family:  Enzyme

Novelty:  0.00030366

Score:  0.946

Data Source:  STRINGDB

CBR3

Tbio

Family:  Enzyme

Novelty:  0.01874422

Score:  0.937

Data Source:  STRINGDB

FMO2

Tbio

Family:  Enzyme

Novelty:  0.02880294

Score:  0.93

Data Source:  STRINGDB

FMO4

Tbio

Family:  Enzyme

Novelty:  0.0411802

Score:  0.929

Data Source:  STRINGDB

HSD11B1

Tclin

Family:  Enzyme

Novelty:  0.00105097

Score:  0.928

Data Source:  STRINGDB

Publication Statistics

PubMed Score  5035.54

PubMed score by year

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PubTator Score  3352.79

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

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3D-structure
Alternative splicing
Complete proteome
Endoplasmic reticulum
Heme
Iron
Lipid metabolism
Membrane
Metal-binding
Microsome

GWAS Trait Find Similar Targets

No Header	No Header
autism spectrum disorder
body mass index
chronotype measurement
cognitive function measurement
intelligence
mathematical ability
mean corpuscular volume
schizophrenia
self reported educational attainment
serum non-albumin protein measurement