CYP2D6

Protein identityUniProt · HPA

UniProt accession

P10635

Gene

CYP2D6

Ensembl

ENSG00000100197

Chromosome

22

Canonical length

497 aa

Protein class

Human disease related genes, Metabolic proteins, Predicted membrane proteins

Subcellular location

Golgi apparatus

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

497 residues, UniProt reviewed canonical sequence.

>P10635|CYP2D6
     1  MGLEALVPLA VIVAIFLLLV DLMHRRQRWA ARYPPGPLPL PGLGNLLHVD FQNTPYCFDQ
    61  LRRRFGDVFS LQLAWTPVVV LNGLAAVREA LVTHGEDTAD RPPVPITQIL GFGPRSQGVF
   121  LARYGPAWRE QRRFSVSTLR NLGLGKKSLE QWVTEEAACL CAAFANHSGR PFRPNGLLDK
   181  AVSNVIASLT CGRRFEYDDP RFLRLLDLAQ EGLKEESGFL REVLNAVPVL LHIPALAGKV
   241  LRFQKAFLTQ LDELLTEHRM TWDPAQPPRD LTEAFLAEME KAKGNPESSF NDENLRIVVA
   301  DLFSAGMVTT STTLAWGLLL MILHPDVQRR VQQEIDDVIG QVRRPEMGDQ AHMPYTTAVI
   361  HEVQRFGDIV PLGVTHMTSR DIEVQGFRIP KGTTLITNLS SVLKDEAVWE KPFRFHPEHF
   421  LDAQGHFVKP EAFLPFSAGR RACLGEPLAR MELFLFFTSL LQHFSFSVPT GQPRPSHHGV
   481  FAFLVSPSPY ELCAVPR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CYP2D6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

386 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CYP2D6.

Disease | ImmuneIEDB

Conditions an epitope on CYP2D6 was assayed in.

• autoimmune hepatitis B and T cell
• hepatitis C B and T cell
• primary biliary cholangitis T cell
• hepatitis B T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against CYP2D6 are reported. Each links to that disease's full target list.

• Hepatitis, Autoimmune 15
• Hepatitis C, Chronic 6

ReferencesPubMed · IEDB

Publications for CYP2D6 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.94

gnomAD pLI

0

gnomAD missense Z

-2

DepMap mean gene effect

0

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• alkaloid catabolic process
• alkaloid metabolic process
• arachidonate metabolic process
• cholesterol metabolic process
• coumarin metabolic process
• estrogen metabolic process
• long-chain fatty acid biosynthetic process
• monoterpenoid metabolic process
• oxidative demethylation
• retinol metabolic process
• steroid metabolic process
• xenobiotic catabolic process
• xenobiotic metabolic process
• isoquinoline alkaloid metabolic process
• negative regulation of organofluorine metabolic process

Molecular functions

• anandamide 11,12 epoxidase activity
• anandamide 14,15 epoxidase activity
• anandamide 8,9 epoxidase activity
• heme binding
• iron ion binding
• monooxygenase activity
• oxidoreductase 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 components

• cytoplasm
• endoplasmic reticulum
• endoplasmic reticulum membrane
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Cytochrome P450
• Cytochrome P450, E-class, group I
• Cytochrome P450, E-class, group I, CYP2D-like
• Cytochrome P450, conserved site
• Cytochrome P450 superfamily
• Cytochrome P450 family 2
• Cytochrome P450

KeywordsUniProt

• Cholesterol metabolism
• Endoplasmic reticulum
• Fatty acid metabolism
• Heme
• Iron
• Lipid metabolism
• Membrane
• Metal-binding
• Microsome
• Monooxygenase
• Oxidoreductase
• Steroid metabolism
• Sterol metabolism