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Cytochrome P450 2D6 (EC 1.14.14.1) (CYPIID6) (Cholesterol 25-hydroxylase) (Cytochrome P450-DB1) (Debrisoquine 4-hydroxylase)

 CP2D6_HUMAN             Reviewed;         497 AA.
P10635; Q16752; Q2XND6; Q2XND7; Q2XNE0; Q6B012; Q6NXU8;
01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
20-DEC-2005, sequence version 2.
25-OCT-2017, entry version 194.
RecName: Full=Cytochrome P450 2D6;
EC=1.14.14.1 {ECO:0000269|PubMed:21576599};
AltName: Full=CYPIID6;
AltName: Full=Cholesterol 25-hydroxylase {ECO:0000305|PubMed:21576599};
AltName: Full=Cytochrome P450-DB1;
AltName: Full=Debrisoquine 4-hydroxylase;
Name=CYP2D6; Synonyms=CYP2DL1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=3410476; DOI=10.1016/0888-7543(88)90100-0;
Gonzalez F.J., Vilbois F., Hardwick J.P., McBride O.W., Nebert D.W.,
Gelboin H.V., Meyer U.A.;
"Human debrisoquine 4-hydroxylase (P450IID1): cDNA and deduced amino
acid sequence and assignment of the CYP2D locus to chromosome 22.";
Genomics 2:174-179(1988).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Liver;
PubMed=3123997; DOI=10.1038/331442a0;
Gonzalez F.J., Skoda R.C., Kimura S., Umeno M., Zanger U.M.,
Nebert D.W., Gelboin H.V., Hardwick J.P., Meyer U.A.;
"Characterization of the common genetic defect in humans deficient in
debrisoquine metabolism.";
Nature 331:442-446(1988).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2574001;
Kimura S., Umeno M., Skoda R.C., Meyer U.A., Gonzalez F.J.;
"The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and
identification of the polymorphic CYP2D6 gene, a related gene, and a
pseudogene.";
Am. J. Hum. Genet. 45:889-904(1989).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE CYP2D6*1), IDENTIFICATION OF
ALLELES CYP2D6*41B; CYP2D6*45A; CYP2D6*45B AND CYP2D6*46, VARIANTS
HIS-26; LYS-155; CYS-296 AND THR-486, AND CHARACTERIZATION OF ISOZYMES
CYP2D6.45 AND CYP2D6.46.
PubMed=15768052; DOI=10.1038/sj.tpj.6500305;
Gaedigk A., Bhathena A., Ndjountche L., Pearce R.E.,
Abdel-Rahman S.M., Alander S.W., Bradford L.D., Rogan P.K.,
Leeder J.S.;
"Identification and characterization of novel sequence variations in
the cytochrome P4502D6 (CYP2D6) gene in African Americans.";
Pharmacogenomics J. 5:173-182(2005).
[5]
ERRATUM.
Gaedigk A., Bhathena A., Ndjountche L., Pearce R.E.,
Abdel-Rahman S.M., Alander S.W., Bradford L.D., Rogan P.K.,
Leeder J.S.;
Pharmacogenomics J. 5:276-276(2005).
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-26.
Koch W.H., Nikoloff D.M., Lu W., Pan R.M., deLeon J., Wedlund P.J.;
"CYP2D6 evolution and allele diversity among human races.";
Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS CYS-296
AND THR-486.
PubMed=10591208; DOI=10.1038/990031;
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
Khan A.S., Lane L., Tilahun Y., Wright H.;
"The DNA sequence of human chromosome 22.";
Nature 402:489-495(1999).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND
VARIANTS CYS-296 AND THR-486.
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[9]
CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
PubMed=21576599; DOI=10.1194/jlr.M014084;
Honda A., Miyazaki T., Ikegami T., Iwamoto J., Maeda T., Hirayama T.,
Saito Y., Teramoto T., Matsuzaki Y.;
"Cholesterol 25-hydroxylation activity of CYP3A.";
J. Lipid Res. 52:1509-1516(2011).
[10]
X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-497 IN COMPLEX WITH HEME,
AND FUNCTION.
PubMed=16352597; DOI=10.1074/jbc.M511232200;
Rowland P., Blaney F.E., Smyth M.G., Jones J.J., Leydon V.R.,
Oxbrow A.K., Lewis C.J., Tennant M.G., Modi S., Eggleston D.S.,
Chenery R.J., Bridges A.M.;
"Crystal structure of human cytochrome P450 2D6.";
J. Biol. Chem. 281:7614-7622(2006).
[11]
VARIANT CYP2D6*9 LYS-281 DEL.
PubMed=1844820;
Tyndale R., Aoyama T., Broly F., Matsunaga T., Inaba T., Kalow W.,
Gelboin H.V., Meyer U.A., Gonzalez F.J.;
"Identification of a new variant CYP2D6 allele lacking the codon
encoding Lys-281: possible association with the poor metabolizer
phenotype.";
Pharmacogenetics 1:26-32(1991).
[12]
VARIANTS CYP2D6*10 SER-34 AND THR-486.
PubMed=8287064;
Yokota H., Tamura S., Furuya H., Kimura S., Watanabe M., Kanazawa I.,
Kondo I., Gonzalez F.J.;
"Evidence for a new variant CYP2D6 allele CYP2D6J in a Japanese
population associated with lower in vivo rates of sparteine
metabolism.";
Pharmacogenetics 3:256-263(1993).
[13]
VARIANT CYP2D6*7 PRO-324.
PubMed=7845481; DOI=10.1007/BF00178963;
Evert B., Griese E.U., Eichelbaum M.;
"A missense mutation in exon 6 of the CYP2D6 gene leading to a
histidine 324 to proline exchange is associated with the poor
metabolizer phenotype of sparteine.";
Naunyn Schmiedebergs Arch. Pharmacol. 350:434-439(1994).
[14]
VARIANT CYP2D6*6B/6C GLU-212.
PubMed=7868129; DOI=10.1007/BF00225204;
Daly A.K., Leathart J.B., London S.J., Idle J.R.;
"An inactive cytochrome P450 CYP2D6 allele containing a deletion and a
base substitution.";
Hum. Genet. 95:337-341(1995).
[15]
VARIANT CYP2D6*17 ILE-107.
PubMed=8971426; DOI=10.1046/j.1365-2125.1996.00489.x;
Masimirembwa C., Persson I., Bertilsson L., Hasler J.,
Ingelman-Sundberg M.;
"A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a
black African population: association with diminished debrisoquine
hydroxylase activity.";
Br. J. Clin. Pharmacol. 42:713-719(1996).
[16]
VARIANT CYP2D6*12 ARG-42.
PubMed=8655150; DOI=10.1007/BF02281880;
Marez D., Legrand M., Sabbagh N., Lo-Guidice J.-M., Boone P.,
Broly F.;
"An additional allelic variant of the CYP2D6 gene causing impaired
metabolism of sparteine.";
Hum. Genet. 97:668-670(1996).
[17]
VARIANTS.
PubMed=9241659;
Marez D., Legrand M., Sabbagh N., Guidice J.M., Spire C.,
Lafitte J.J., Meyer U.A., Broly F.;
"Polymorphism of the cytochrome P450 CYP2D6 gene in a European
population: characterization of 48 mutations and 53 alleles, their
frequencies and evolution.";
Pharmacogenetics 7:193-202(1997).
[18]
VARIANT CYP2D6*14 ARG-169.
PubMed=10064570;
Wang S.L., Lai M.D., Huang J.D.;
"G169R mutation diminishes the metabolic activity of CYP2D6 in
Chinese.";
Drug Metab. Dispos. 27:385-388(1999).
[19]
VARIANTS MET-11; HIS-26; SER-34; MET-91; ARG-94; ILE-107; ILE-120;
LYS-155; SER-237; CYS-296; LYS-418; ALA-469; TYR-478 AND THR-486.
PubMed=15469410; DOI=10.1517/14622416.5.7.895;
Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q.,
McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.;
"Genetic variation in eleven phase I drug metabolism genes in an
ethnically diverse population.";
Pharmacogenomics 5:895-931(2004).
[20]
VARIANTS CYP2D6*87 VAL-5; GLN-25; CYP2D6*10 SER-34; CYP2D6*88 ALA-104;
CYP2D6*89 SER-142; CYP2D6*90 ARG-147; CYP2D6*91 SER-161; LEU-164;
LYS-215; SER-219; CYP2D6*93 PRO-249; CYP2D6*2 CYS-296; MET-327;
ASN-336; CYP2D6*94 GLY-337; MET-342; GLN-344; CYS-440; CYP2D6*97
LEU-457; CYP2D6*98 ASP-463; CYP2D6*10/2 THR-486 AND CYS-497.
PubMed=25469868; DOI=10.1111/bcpt.12363;
Dai D.P., Geng P.W., Wang S.H., Cai J., Hu L.M., Nie J.J., Hu J.H.,
Hu G.X., Cai J.P.;
"In vitro functional assessment of 22 newly identified CYP2D6 allelic
variants in the Chinese population.";
Basic Clin. Pharmacol. Toxicol. 117:39-43(2015).
-!- FUNCTION: 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.
{ECO:0000269|PubMed:16352597}.
-!- CATALYTIC ACTIVITY: RH + [reduced NADPH--hemoprotein reductase] +
O(2) = ROH + [oxidized NADPH--hemoprotein reductase] + H(2)O.
{ECO:0000269|PubMed:21576599}.
-!- COFACTOR:
Name=heme; Xref=ChEBI:CHEBI:30413;
-!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
membrane protein. Microsome membrane
{ECO:0000269|PubMed:21576599}; Peripheral membrane protein.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=P10635-1; Sequence=Displayed;
Name=2;
IsoId=P10635-2; Sequence=VSP_044486;
Note=No experimental confirmation available.;
-!- INDUCTION: By pregnancy.
-!- POLYMORPHISM: Genetic variations in CYP2D6 are the cause of poor
drug metabolism CYP2D6-related [MIM:608902]. The CYP2D6 gene is
highly polymorphic. CYP2D6 activity ranges widely within a
population comprising ultrarapid (UM), extensive (EM),
intermediate (IM) and poor (PM) metabolizer phenotypes. UM and PM
are those most at risk for treatment failure or dose-dependent
drug toxicity, respectively. Of the Caucasian populations of
Europe and North America, 5%-10% are of the PM phenotype and are
unable to metabolize the antihypersensitive drug debrisoquine and
numerous other drugs. Different alleles are known, including
CYP2D6*1 (PubMed:15768052), CYP2D6*2 (PubMed:25469868),
CYP2D6*6B/6C (PubMed:7868129), CYP2D6*7 also known CYP2D6E
(PubMed:7845481), CYP2D6*9 also known CYP2D6C (PubMed:1844820),
CYP2D6*10 also known CYP2D6J (PubMed:8287064, PubMed:25469868),
CYP2D6*12 (PubMed:8655150), CYP2D6*14 (PubMed:10064570), CYP2D6*17
also known CYP2D6Z (PubMed:8971426), CYP2D6*41B (PubMed:15768052),
CYP2D6*45A (PubMed:15768052), CYP2D6*45B (PubMed:15768052),
CYP2D6*46 (PubMed:15768052), CYP2D6*87 (PubMed:25469868),
CYP2D6*88 (PubMed:25469868), CYP2D6*89 (PubMed:25469868),
CYP2D6*90 (PubMed:25469868), CYP2D6*91 (PubMed:25469868),
CYP2D6*93 (PubMed:25469868), C CYP2D6*94 (PubMed:25469868),
CYP2D6*97 (PubMed:25469868) and CYP2D6*98 (PubMed:25469868).
Isozymes CYP2D6.45 (Lys-155, Cys-296 and Thr-486) and CYP2D6.46
(His-26, Lys-155, Cys-296 and Thr-486) are functional
(PubMed:15768052). {ECO:0000269|PubMed:10064570,
ECO:0000269|PubMed:15768052, ECO:0000269|PubMed:16352597,
ECO:0000269|PubMed:1844820, ECO:0000269|PubMed:25469868,
ECO:0000269|PubMed:7845481, ECO:0000269|PubMed:7868129,
ECO:0000269|PubMed:8655150, ECO:0000269|PubMed:8971426}.
-!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee;
Note=CYP2D6 alleles;
URL="http://www.cypalleles.ki.se/cyp2d6.htm";
-!- WEB RESOURCE: Name=Wikipedia; Note=CYP2D6 entry;
URL="https://en.wikipedia.org/wiki/CYP2D6";
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EMBL; M20403; AAA52153.1; -; mRNA.
EMBL; X08006; CAA30807.1; -; mRNA.
EMBL; M33388; AAA53500.1; -; Genomic_DNA.
EMBL; AY545216; AAS55001.1; -; Genomic_DNA.
EMBL; DQ282144; ABB77895.1; -; Genomic_DNA.
EMBL; DQ282145; ABB77896.1; -; Genomic_DNA.
EMBL; DQ282146; ABB77897.1; -; Genomic_DNA.
EMBL; DQ282151; ABB77899.1; -; Genomic_DNA.
EMBL; DQ282154; ABB77902.1; -; Genomic_DNA.
EMBL; DQ282155; ABB77903.1; -; Genomic_DNA.
EMBL; BX247885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC066877; AAH66877.1; -; mRNA.
EMBL; BC075023; AAH75023.1; -; mRNA.
EMBL; BC075024; AAH75024.1; -; mRNA.
CCDS; CCDS33657.1; -. [P10635-2]
CCDS; CCDS46721.1; -. [P10635-1]
PIR; S01199; O4HUD1.
RefSeq; NP_000097.3; NM_000106.5. [P10635-1]
RefSeq; NP_001020332.2; NM_001025161.2. [P10635-2]
UniGene; Hs.648256; -.
PDB; 2F9Q; X-ray; 3.00 A; A/B/C/D=34-497.
PDB; 3QM4; X-ray; 2.85 A; A/B=34-497.
PDB; 3TBG; X-ray; 2.10 A; A/B/C/D=34-497.
PDB; 3TDA; X-ray; 2.67 A; A/B/C/D=34-497.
PDB; 4WNT; X-ray; 2.60 A; A/B=34-497.
PDB; 4WNU; X-ray; 2.26 A; A/B/C/D=34-497.
PDB; 4WNV; X-ray; 2.35 A; A/B/C/D=48-497.
PDB; 4WNW; X-ray; 3.30 A; A/B=34-497.
PDB; 4XRY; X-ray; 2.50 A; A/B/C/D=34-497.
PDB; 4XRZ; X-ray; 2.40 A; A/B/C/D=34-497.
PDB; 5TFT; X-ray; 2.71 A; A/B/C/D=34-497.
PDB; 5TFU; X-ray; 2.75 A; A/B/C/D=34-497.
PDBsum; 2F9Q; -.
PDBsum; 3QM4; -.
PDBsum; 3TBG; -.
PDBsum; 3TDA; -.
PDBsum; 4WNT; -.
PDBsum; 4WNU; -.
PDBsum; 4WNV; -.
PDBsum; 4WNW; -.
PDBsum; 4XRY; -.
PDBsum; 4XRZ; -.
PDBsum; 5TFT; -.
PDBsum; 5TFU; -.
ProteinModelPortal; P10635; -.
SMR; P10635; -.
BioGrid; 107940; 4.
STRING; 9606.ENSP00000353820; -.
BindingDB; P10635; -.
ChEMBL; CHEMBL289; -.
DrugBank; DB01562; 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
DrugBank; DB01472; 4-Methoxyamphetamine.
DrugBank; DB05812; Abiraterone.
DrugBank; DB01193; Acebutolol.
DrugBank; DB00316; Acetaminophen.
DrugBank; DB03128; Acetylcholine.
DrugBank; DB01426; Ajmaline.
DrugBank; DB00918; Almotriptan.
DrugBank; DB06203; Alogliptin.
DrugBank; DB00866; Alprenolol.
DrugBank; DB01424; Aminophenazone.
DrugBank; DB01118; Amiodarone.
DrugBank; DB00321; Amitriptyline.
DrugBank; DB00381; Amlodipine.
DrugBank; DB00613; Amodiaquine.
DrugBank; DB00543; Amoxapine.
DrugBank; DB00182; Amphetamine.
DrugBank; DB00701; Amprenavir.
DrugBank; DB00276; Amsacrine.
DrugBank; DB01435; Antipyrine.
DrugBank; DB01429; Aprindine.
DrugBank; DB01274; Arformoterol.
DrugBank; DB01238; Aripiprazole.
DrugBank; DB06697; Artemether.
DrugBank; DB06216; Asenapine.
DrugBank; DB00637; Astemizole.
DrugBank; DB00289; Atomoxetine.
DrugBank; DB01076; Atorvastatin.
DrugBank; DB00972; Azelastine.
DrugBank; DB00245; Benzatropine.
DrugBank; DB06770; Benzyl alcohol.
DrugBank; DB01244; Bepridil.
DrugBank; DB00195; Betaxolol.
DrugBank; DB01128; Bicalutamide.
DrugBank; DB04889; Bicifadine.
DrugBank; DB00810; Biperiden.
DrugBank; DB00612; Bisoprolol.
DrugBank; DB00188; Bortezomib.
DrugBank; DB09128; Brexpiprazole.
DrugBank; DB00835; Brompheniramine.
DrugBank; DB06726; Bufuralol.
DrugBank; DB00297; Bupivacaine.
DrugBank; DB00921; Buprenorphine.
DrugBank; DB01156; Bupropion.
DrugBank; DB00490; Buspirone.
DrugBank; DB00201; Caffeine.
DrugBank; DB01197; Captopril.
DrugBank; DB00748; Carbinoxamine.
DrugBank; DB06016; Cariprazine.
DrugBank; DB00521; Carteolol.
DrugBank; DB01136; Carvedilol.
DrugBank; DB00482; Celecoxib.
DrugBank; DB00567; Cephalexin.
DrugBank; DB00439; Cerivastatin.
DrugBank; DB00185; Cevimeline.
DrugBank; DB00475; Chlordiazepoxide.
DrugBank; DB00608; Chloroquine.
DrugBank; DB01114; Chlorphenamine.
DrugBank; DB00477; Chlorpromazine.
DrugBank; DB00356; Chlorzoxazone.
DrugBank; DB00169; Cholecalciferol.
DrugBank; DB01410; Ciclesonide.
DrugBank; DB01166; Cilostazol.
DrugBank; DB00501; Cimetidine.
DrugBank; DB01012; Cinacalcet.
DrugBank; DB00568; Cinnarizine.
DrugBank; DB00604; Cisapride.
DrugBank; DB00215; Citalopram.
DrugBank; DB00283; Clemastine.
DrugBank; DB04920; Clevidipine.
DrugBank; DB00349; Clobazam.
DrugBank; DB01242; Clomipramine.
DrugBank; DB00575; Clonidine.
DrugBank; DB00257; Clotrimazole.
DrugBank; DB00363; Clozapine.
DrugBank; DB09065; Cobicistat.
DrugBank; DB00907; Cocaine.
DrugBank; DB00318; Codeine.
DrugBank; DB00924; Cyclobenzaprine.
DrugBank; DB00531; Cyclophosphamide.
DrugBank; DB00091; Cyclosporine.
DrugBank; DB04839; Cyproterone acetate.
DrugBank; DB06292; Dapagliflozin.
DrugBank; DB00496; Darifenacin.
DrugBank; DB09183; Dasabuvir.
DrugBank; DB04840; Debrisoquin.
DrugBank; DB00705; Delavirdine.
DrugBank; DB06512; Deramciclane.
DrugBank; DB01151; Desipramine.
DrugBank; DB00967; Desloratadine.
DrugBank; DB01234; Dexamethasone.
DrugBank; DB09555; Dexchlorpheniramine maleate.
DrugBank; DB01191; Dexfenfluramine.
DrugBank; DB00633; Dexmedetomidine.
DrugBank; DB06701; Dexmethylphenidate.
DrugBank; DB01576; Dextroamphetamine.
DrugBank; DB00514; Dextromethorphan.
DrugBank; DB00647; Dextropropoxyphene.
DrugBank; DB01551; Dihydrocodeine.
DrugBank; DB00343; Diltiazem.
DrugBank; DB01093; Dimethyl sulfoxide.
DrugBank; DB01075; Diphenhydramine.
DrugBank; DB00822; Disulfiram.
DrugBank; DB00757; Dolasetron.
DrugBank; DB01184; Domperidone.
DrugBank; DB00843; Donepezil.
DrugBank; DB00988; Dopamine.
DrugBank; DB00590; Doxazosin.
DrugBank; DB01142; Doxepin.
DrugBank; DB00997; Doxorubicin.
DrugBank; DB04855; Dronedarone.
DrugBank; DB00476; Duloxetine.
DrugBank; DB00625; Efavirenz.
DrugBank; DB00216; Eletriptan.
DrugBank; DB09039; Eliglustat.
DrugBank; DB01228; Encainide.
DrugBank; DB06735; Enclomiphene.
DrugBank; DB00494; Entacapone.
DrugBank; DB08899; Enzalutamide.
DrugBank; DB00751; Epinastine.
DrugBank; DB00530; Erlotinib.
DrugBank; DB01175; Escitalopram.
DrugBank; DB06678; Esmirtazapine.
DrugBank; DB01466; Ethylmorphine.
DrugBank; DB01628; Etoricoxib.
DrugBank; DB01023; Felodipine.
DrugBank; DB00574; Fenfluramine.
DrugBank; DB06702; Fesoterodine.
DrugBank; DB00950; Fexofenadine.
DrugBank; DB08868; Fingolimod.
DrugBank; DB01195; Flecainide.
DrugBank; DB04841; Flunarizine.
DrugBank; DB00472; Fluoxetine.
DrugBank; DB00623; Fluphenazine.
DrugBank; DB01095; Fluvastatin.
DrugBank; DB00176; Fluvoxamine.
DrugBank; DB00983; Formoterol.
DrugBank; DB00674; Galantamine.
DrugBank; DB00317; Gefitinib.
DrugBank; DB01437; Glutethimide.
DrugBank; DB08909; Glycerol Phenylbutyrate.
DrugBank; DB00889; Granisetron.
DrugBank; DB01218; Halofantrine.
DrugBank; DB00502; Haloperidol.
DrugBank; DB01159; Halothane.
DrugBank; DB05381; Histamine.
DrugBank; DB00956; Hydrocodone.
DrugBank; DB00327; Hydromorphone.
DrugBank; DB01611; Hydroxychloroquine.
DrugBank; DB01005; Hydroxyurea.
DrugBank; DB00557; Hydroxyzine.
DrugBank; DB09053; Ibrutinib.
DrugBank; DB01177; Idarubicin.
DrugBank; DB04946; Iloperidone.
DrugBank; DB00619; Imatinib.
DrugBank; DB00458; Imipramine.
DrugBank; DB00224; Indinavir.
DrugBank; DB00332; Ipratropium bromide.
DrugBank; DB01029; Irbesartan.
DrugBank; DB00951; Isoniazid.
DrugBank; DB01167; Itraconazole.
DrugBank; DB09570; Ixazomib.
DrugBank; DB01026; Ketoconazole.
DrugBank; DB00598; Labetalol.
DrugBank; DB00448; Lansoprazole.
DrugBank; DB00528; Lercanidipine.
DrugBank; DB01235; Levodopa.
DrugBank; DB08918; Levomilnacipran.
DrugBank; DB13139; Levosalbutamol.
DrugBank; DB00281; Lidocaine.
DrugBank; DB00589; Lisuride.
DrugBank; DB01206; Lomustine.
DrugBank; DB00836; Loperamide.
DrugBank; DB01601; Lopinavir.
DrugBank; DB00455; Loratadine.
DrugBank; DB04871; Lorcaserin.
DrugBank; DB00227; Lovastatin.
DrugBank; DB06708; Lumefantrine.
DrugBank; DB00934; Maprotiline.
DrugBank; DB00358; Mefloquine.
DrugBank; DB00532; Mephenytoin.
DrugBank; DB06691; Mepyramine.
DrugBank; DB01071; Mequitazine.
DrugBank; DB00933; Mesoridazine.
DrugBank; DB00333; Methadone.
DrugBank; DB01577; Methamphetamine.
DrugBank; DB00703; Methazolamide.
DrugBank; DB00763; Methimazole.
DrugBank; DB01403; Methotrimeprazine.
DrugBank; DB00553; Methoxsalen.
DrugBank; DB01028; Methoxyflurane.
DrugBank; DB09543; Methyl salicylate.
DrugBank; DB06800; Methylnaltrexone.
DrugBank; DB00422; Methylphenidate.
DrugBank; DB01107; Methyprylon.
DrugBank; DB01233; Metoclopramide.
DrugBank; DB00264; Metoprolol.
DrugBank; DB00379; Mexiletine.
DrugBank; DB06148; Mianserin.
DrugBank; DB01388; Mibefradil.
DrugBank; DB01110; Miconazole.
DrugBank; DB00211; Midodrine.
DrugBank; DB00834; Mifepristone.
DrugBank; DB00805; Minaprine.
DrugBank; DB08893; Mirabegron.
DrugBank; DB00370; Mirtazapine.
DrugBank; DB01171; Moclobemide.
DrugBank; DB00295; Morphine.
DrugBank; DB09049; Naloxegol.
DrugBank; DB00731; Nateglinide.
DrugBank; DB04861; Nebivolol.
DrugBank; DB01149; Nefazodone.
DrugBank; DB00220; Nelfinavir.
DrugBank; DB09048; Netupitant.
DrugBank; DB00238; Nevirapine.
DrugBank; DB00627; Niacin.
DrugBank; DB00622; Nicardipine.
DrugBank; DB00699; Nicergoline.
DrugBank; DB02701; Nicotinamide.
DrugBank; DB00184; Nicotine.
DrugBank; DB01115; Nifedipine.
DrugBank; DB04868; Nilotinib.
DrugBank; DB00336; Nitrofural.
DrugBank; DB00540; Nortriptyline.
DrugBank; DB00334; Olanzapine.
DrugBank; DB00338; Omeprazole.
DrugBank; DB00904; Ondansetron.
DrugBank; DB04938; Ospemifene.
DrugBank; DB01096; Oxamniquine.
DrugBank; DB01580; Oxprenolol.
DrugBank; DB01062; Oxybutynin.
DrugBank; DB00497; Oxycodone.
DrugBank; DB06412; Oxymetholone.
DrugBank; DB01192; Oxymorphone.
DrugBank; DB01267; Paliperidone.
DrugBank; DB00377; Palonosetron.
DrugBank; DB06603; Panobinostat.
DrugBank; DB00715; Paroxetine.
DrugBank; DB06589; Pazopanib.
DrugBank; DB00022; Peginterferon alfa-2b.
DrugBank; DB00738; Pentamidine.
DrugBank; DB01186; Pergolide.
DrugBank; DB01074; Perhexiline.
DrugBank; DB00850; Perphenazine.
DrugBank; DB00454; Pethidine.
DrugBank; DB03783; Phenacetin.
DrugBank; DB00914; Phenformin.
DrugBank; DB00191; Phentermine.
DrugBank; DB01100; Pimozide.
DrugBank; DB00960; Pindolol.
DrugBank; DB01132; Pioglitazone.
DrugBank; DB00592; Piperazine.
DrugBank; DB01621; Pipotiazine.
DrugBank; DB08901; Ponatinib.
DrugBank; DB00175; Pravastatin.
DrugBank; DB01058; Praziquantel.
DrugBank; DB01087; Primaquine.
DrugBank; DB01035; Procainamide.
DrugBank; DB00433; Prochlorperazine.
DrugBank; DB00396; Progesterone.
DrugBank; DB01131; Proguanil.
DrugBank; DB00420; Promazine.
DrugBank; DB01069; Promethazine.
DrugBank; DB01182; Propafenone.
DrugBank; DB00818; Propofol.
DrugBank; DB09396; Propoxyphene napsylate.
DrugBank; DB00571; Propranolol.
DrugBank; DB00344; Protriptyline.
DrugBank; DB00852; Pseudoephedrine.
DrugBank; DB00205; Pyrimethamine.
DrugBank; DB01224; Quetiapine.
DrugBank; DB00908; Quinidine.
DrugBank; DB00468; Quinine.
DrugBank; DB01129; Rabeprazole.
DrugBank; DB00863; Ranitidine.
DrugBank; DB00243; Ranolazine.
DrugBank; DB00234; Reboxetine.
DrugBank; DB00409; Remoxipride.
DrugBank; DB01201; Rifapentine.
DrugBank; DB00734; Risperidone.
DrugBank; DB00503; Ritonavir.
DrugBank; DB00989; Rivastigmine.
DrugBank; DB09291; Rolapitant.
DrugBank; DB00268; Ropinirole.
DrugBank; DB00296; Ropivacaine.
DrugBank; DB00412; Rosiglitazone.
DrugBank; DB05271; Rotigotine.
DrugBank; DB12332; Rucaparib.
DrugBank; DB01698; Rutin.
DrugBank; DB01232; Saquinavir.
DrugBank; DB01037; Selegiline.
DrugBank; DB06144; Sertindole.
DrugBank; DB01104; Sertraline.
DrugBank; DB00203; Sildenafil.
DrugBank; DB00641; Simvastatin.
DrugBank; DB06819; Sodium phenylbutyrate.
DrugBank; DB00398; Sorafenib.
DrugBank; DB06727; Sparteine.
DrugBank; DB09118; Stiripentol.
DrugBank; DB06820; Sulconazole.
DrugBank; DB00259; Sulfanilamide.
DrugBank; DB06729; Sulfaphenazole.
DrugBank; DB00675; Tamoxifen.
DrugBank; DB00706; Tamsulosin.
DrugBank; DB06204; Tapentadol.
DrugBank; DB01079; Tegaserod.
DrugBank; DB00976; Telithromycin.
DrugBank; DB06287; Temsirolimus.
DrugBank; DB00857; Terbinafine.
DrugBank; DB00342; Terfenadine.
DrugBank; DB04905; Tesmilifene.
DrugBank; DB04844; Tetrabenazine.
DrugBank; DB00277; Theophylline.
DrugBank; DB00679; Thioridazine.
DrugBank; DB01623; Thiothixene.
DrugBank; DB08816; Ticagrelor.
DrugBank; DB00208; Ticlopidine.
DrugBank; DB00373; Timolol.
DrugBank; DB01007; Tioconazole.
DrugBank; DB01409; Tiotropium.
DrugBank; DB00932; Tipranavir.
DrugBank; DB01036; Tolterodine.
DrugBank; DB05109; Trabectedin.
DrugBank; DB00193; Tramadol.
DrugBank; DB00752; Tranylcypromine.
DrugBank; DB00656; Trazodone.
DrugBank; DB00726; Trimipramine.
DrugBank; DB00792; Tripelennamine.
DrugBank; DB00427; Triprolidine.
DrugBank; DB00209; Trospium.
DrugBank; DB09076; Umeclidinium.
DrugBank; DB08881; Vemurafenib.
DrugBank; DB00285; Venlafaxine.
DrugBank; DB00661; Verapamil.
DrugBank; DB06684; Vilazodone.
DrugBank; DB00570; Vinblastine.
DrugBank; DB00361; Vinorelbine.
DrugBank; DB09068; Vortioxetine.
DrugBank; DB01392; Yohimbine.
DrugBank; DB00549; Zafirlukast.
DrugBank; DB00943; Zalcitabine.
DrugBank; DB00246; Ziprasidone.
DrugBank; DB00425; Zolpidem.
DrugBank; DB01624; Zuclopenthixol.
GuidetoPHARMACOLOGY; 1329; -.
SwissLipids; SLP:000001204; -.
iPTMnet; P10635; -.
PhosphoSitePlus; P10635; -.
BioMuta; CYP2D6; -.
DMDM; 84028191; -.
PaxDb; P10635; -.
PeptideAtlas; P10635; -.
PRIDE; P10635; -.
Ensembl; ENST00000359033; ENSP00000351927; ENSG00000100197. [P10635-2]
Ensembl; ENST00000360608; ENSP00000353820; ENSG00000100197. [P10635-1]
Ensembl; ENST00000612990; ENSP00000483677; ENSG00000275211.
GeneID; 1565; -.
KEGG; hsa:1565; -.
UCSC; uc003bce.4; human. [P10635-1]
CTD; 1565; -.
DisGeNET; 1565; -.
EuPathDB; HostDB:ENSG00000100197.20; -.
GeneCards; CYP2D6; -.
HGNC; HGNC:2625; CYP2D6.
HPA; HPA045223; -.
MalaCards; CYP2D6; -.
MIM; 124030; gene.
MIM; 608902; phenotype.
neXtProt; NX_P10635; -.
OpenTargets; ENSG00000100197; -.
Orphanet; 413667; Antidepressant or antipsychotics toxicity or dose selection.
Orphanet; 240867; Codeine toxicity.
Orphanet; 240947; Resistance to tamoxifene.
PharmGKB; PA128; -.
eggNOG; KOG0156; Eukaryota.
eggNOG; COG2124; LUCA.
GeneTree; ENSGT00900000140799; -.
HOVERGEN; HBG015789; -.
InParanoid; P10635; -.
KO; K17712; -.
OMA; DIELQGF; -.
OrthoDB; EOG091G0BT8; -.
PhylomeDB; P10635; -.
TreeFam; TF352043; -.
BRENDA; 1.14.14.1; 2681.
BRENDA; 1.14.99.38; 2681.
Reactome; R-HSA-211935; Fatty acids.
Reactome; R-HSA-211958; Miscellaneous substrates.
Reactome; R-HSA-211981; Xenobiotics.
Reactome; R-HSA-211999; CYP2E1 reactions.
SABIO-RK; P10635; -.
EvolutionaryTrace; P10635; -.
GeneWiki; CYP2D6; -.
GenomeRNAi; 1565; -.
PRO; PR:P10635; -.
Proteomes; UP000005640; Chromosome 22.
Bgee; ENSG00000100197; -.
CleanEx; HS_CYP2D6; -.
ExpressionAtlas; P10635; baseline and differential.
Genevisible; P10635; HS.
GO; GO:0005783; C:endoplasmic reticulum; TAS:BHF-UCL.
GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
GO; GO:0031090; C:organelle membrane; IEA:UniProtKB-SubCell.
GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
GO; GO:0008144; F:drug binding; IDA:BHF-UCL.
GO; GO:0020037; F:heme binding; IDA:UniProtKB.
GO; GO:0005506; F:iron ion binding; IEA:InterPro.
GO; GO:0004497; F:monooxygenase activity; IDA:BHF-UCL.
GO; GO:0016491; F:oxidoreductase activity; IDA:BHF-UCL.
GO; GO:0016712; F: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; TAS:Reactome.
GO; GO:0019825; F:oxygen binding; TAS:Reactome.
GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
GO; GO:0009822; P:alkaloid catabolic process; IDA:BHF-UCL.
GO; GO:0009820; P:alkaloid metabolic process; IDA:BHF-UCL.
GO; GO:0019369; P:arachidonic acid metabolic process; IBA:GO_Central.
GO; GO:0009804; P:coumarin metabolic process; IDA:BHF-UCL.
GO; GO:0042737; P:drug catabolic process; IDA:BHF-UCL.
GO; GO:0017144; P:drug metabolic process; IDA:BHF-UCL.
GO; GO:0046483; P:heterocycle metabolic process; IDA:BHF-UCL.
GO; GO:0033076; P:isoquinoline alkaloid metabolic process; IDA:BHF-UCL.
GO; GO:0016098; P:monoterpenoid metabolic process; IDA:BHF-UCL.
GO; GO:0051100; P:negative regulation of binding; IDA:BHF-UCL.
GO; GO:0090350; P:negative regulation of cellular organofluorine metabolic process; IDA:BHF-UCL.
GO; GO:0055114; P:oxidation-reduction process; IDA:BHF-UCL.
GO; GO:0070989; P:oxidative demethylation; IDA:BHF-UCL.
GO; GO:0008202; P:steroid metabolic process; IMP:BHF-UCL.
GO; GO:0006805; P:xenobiotic metabolic process; TAS:BHF-UCL.
Gene3D; 1.10.630.10; -; 1.
InterPro; IPR001128; Cyt_P450.
InterPro; IPR017972; Cyt_P450_CS.
InterPro; IPR002401; Cyt_P450_E_grp-I.
InterPro; IPR008069; Cyt_P450_E_grp-I_CYP2D-like.
InterPro; IPR036396; Cyt_P450_sf.
Pfam; PF00067; p450; 1.
PRINTS; PR00463; EP450I.
PRINTS; PR01686; EP450ICYP2D.
PRINTS; PR00385; P450.
SUPFAM; SSF48264; SSF48264; 1.
PROSITE; PS00086; CYTOCHROME_P450; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Complete proteome;
Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane;
Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Polymorphism;
Reference proteome; Steroid metabolism; Sterol metabolism.
CHAIN 1 497 Cytochrome P450 2D6.
/FTId=PRO_0000051731.
METAL 443 443 Iron (heme axial ligand).
BINDING 301 301 Substrate. {ECO:0000305}.
VAR_SEQ 118 168 Missing (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_044486.
VARIANT 5 5 A -> V (in allele CYP2D6*87;
dbSNP:rs773790593).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072764.
VARIANT 11 11 V -> M (in allele CYP2D6*35;
dbSNP:rs769258).
{ECO:0000269|PubMed:15469410}.
/FTId=VAR_008366.
VARIANT 25 25 R -> Q (in dbSNP:rs138417770).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072765.
VARIANT 26 26 R -> H (in allele CYP2D6*21 and allele
CYP2D6*46; dbSNP:rs28371696).
{ECO:0000269|PubMed:15469410,
ECO:0000269|PubMed:15768052,
ECO:0000269|Ref.6}.
/FTId=VAR_008367.
VARIANT 28 28 R -> C (in allele CYP2D6*22;
dbSNP:rs138100349).
/FTId=VAR_008368.
VARIANT 34 34 P -> S (in allele CYP2D6*10 and allele
CYP2D6*14; poor debrisquone metabolism;
dbSNP:rs1065852).
{ECO:0000269|PubMed:15469410,
ECO:0000269|PubMed:25469868,
ECO:0000269|PubMed:8287064}.
/FTId=VAR_008336.
VARIANT 42 42 G -> R (in allele CYP2D6*12; impaired
metabolism of sparteine;
dbSNP:rs5030862).
{ECO:0000269|PubMed:8655150}.
/FTId=VAR_001256.
VARIANT 85 85 A -> V (in allele CYP2D6*23;
dbSNP:rs267608310).
/FTId=VAR_008369.
VARIANT 91 91 L -> M (in dbSNP:rs28371703).
{ECO:0000269|PubMed:15469410}.
/FTId=VAR_024720.
VARIANT 94 94 H -> R (in dbSNP:rs28371704).
{ECO:0000269|PubMed:15469410}.
/FTId=VAR_024721.
VARIANT 104 104 V -> A (in allele CYP2D6*88;
dbSNP:rs76187628).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072766.
VARIANT 107 107 T -> I (in allele CYP2D6*17; poor
debrisquone metabolism;
dbSNP:rs28371706).
{ECO:0000269|PubMed:15469410,
ECO:0000269|PubMed:8971426}.
/FTId=VAR_008337.
VARIANT 120 120 F -> I (in dbSNP:rs1135822).
{ECO:0000269|PubMed:15469410}.
/FTId=VAR_024722.
VARIANT 142 142 L -> S (in allele CYP2D6*89; >90%
decrease of monooxygenase activity
towards dextromethorphan and bufuralol;
dbSNP:rs375135093).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072767.
VARIANT 147 147 K -> R (in allele CYP2D6*90;
dbSNP:rs569229126).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072768.
VARIANT 155 155 E -> K (in allele CYP2D6*45A, allele
CYP2D6*45B and allele CYP2D6*46;
dbSNP:rs28371710).
{ECO:0000269|PubMed:15469410,
ECO:0000269|PubMed:15768052}.
/FTId=VAR_024723.
VARIANT 161 161 C -> S (in allele CYP2D6*91).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072769.
VARIANT 164 164 F -> L. {ECO:0000269|PubMed:25469868}.
/FTId=VAR_072770.
VARIANT 169 169 G -> R (in allele CYP2D6*14; poor
debrisquone metabolism; dbSNP:rs5030865).
{ECO:0000269|PubMed:10064570}.
/FTId=VAR_008338.
VARIANT 212 212 G -> E (in allele CYP2D6*6B and allele
CYP2D6*6C; dbSNP:rs5030866).
{ECO:0000269|PubMed:7868129}.
/FTId=VAR_008339.
VARIANT 215 215 E -> K (>90% decrease of monooxygenase
activity towards dextromethorphan and
bufuralol; dbSNP:rs567606867).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072771.
VARIANT 219 219 F -> S (in dbSNP:rs371793722).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072772.
VARIANT 231 231 L -> P (in dbSNP:rs17002853).
/FTId=VAR_045679.
VARIANT 237 237 A -> S (in allele CYP2D6*33;
dbSNP:rs28371717).
{ECO:0000269|PubMed:15469410}.
/FTId=VAR_008370.
VARIANT 249 249 T -> P (in allele CYP2D6*93; >90%
decrease of monooxygenase activity
towards dextromethorphan and bufuralol).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072773.
VARIANT 281 281 Missing (in allele CYP2D6*9).
{ECO:0000269|PubMed:1844820}.
/FTId=VAR_008347.
VARIANT 296 296 R -> C (in allele CYP2D6*2, allele
CYP2D6*12, allele CYP2D6*14, allele
CYP2D6*17, allele CYP2D6*45A, allele
CYP2D6*45B and allele CYP2D6*46; slightly
decrease of monooxygenase activity
towards bufuralol; dbSNP:rs16947).
{ECO:0000269|PubMed:10591208,
ECO:0000269|PubMed:15469410,
ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:15768052,
ECO:0000269|PubMed:25469868}.
/FTId=VAR_008340.
VARIANT 297 297 I -> L (in allele CYP2D6*24).
/FTId=VAR_008371.
VARIANT 300 300 A -> G (in dbSNP:rs1058170).
/FTId=VAR_045680.
VARIANT 311 311 S -> L (in dbSNP:rs1800754).
/FTId=VAR_014633.
VARIANT 324 324 H -> P (in allele CYP2D6*7; loss of
activity; dbSNP:rs5030867).
{ECO:0000269|PubMed:7845481}.
/FTId=VAR_008348.
VARIANT 327 327 V -> M. {ECO:0000269|PubMed:25469868}.
/FTId=VAR_072774.
VARIANT 329 329 R -> L (in dbSNP:rs3915951).
/FTId=VAR_059150.
VARIANT 336 336 D -> N (in dbSNP:rs745746329).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072775.
VARIANT 337 337 D -> G (in allele CYP2D6*94;
dbSNP:rs748712690).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072776.
VARIANT 342 342 V -> M (in dbSNP:rs750996195).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072777.
VARIANT 343 343 R -> G (in allele CYP2D6*25;
dbSNP:rs267608295).
/FTId=VAR_008372.
VARIANT 344 344 R -> Q (in dbSNP:rs76088846).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072778.
VARIANT 365 365 R -> H (in dbSNP:rs1058172).
/FTId=VAR_045681.
VARIANT 369 369 I -> T (in allele CYP2D6*26).
/FTId=VAR_008373.
VARIANT 373 373 G -> S (in dbSNP:rs2856959).
/FTId=VAR_059151.
VARIANT 410 410 E -> K (in allele CYP2D6*27;
dbSNP:rs769157652).
/FTId=VAR_008374.
VARIANT 418 418 E -> K (in dbSNP:rs149157808).
{ECO:0000269|PubMed:15469410}.
/FTId=VAR_024724.
VARIANT 440 440 R -> C (>90% decrease of monooxygenase
activity towards dextromethorphan and
bufuralol; dbSNP:rs777560972).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072779.
VARIANT 457 457 F -> L (in allele CYP2D6*97).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072780.
VARIANT 463 463 H -> D (in allele CYP2D6*98).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072781.
VARIANT 469 469 P -> A (in dbSNP:rs1135833).
{ECO:0000269|PubMed:15469410}.
/FTId=VAR_024725.
VARIANT 478 478 H -> Y (in dbSNP:rs28371735).
{ECO:0000269|PubMed:15469410}.
/FTId=VAR_024726.
VARIANT 486 486 S -> T (in allele CYP2D6*2, allele
CYP2D6*10, allele CYP2D6*12, allele
CYP2D6*14, allele CYP2D6*17, allele
CYP2D6*45A, allele CYP2D6*45B and allele
CYP2D6*46; impaired metabolism of
sparteine; dbSNP:rs1135840).
{ECO:0000269|PubMed:10591208,
ECO:0000269|PubMed:15469410,
ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:15768052,
ECO:0000269|PubMed:25469868,
ECO:0000269|PubMed:8287064}.
/FTId=VAR_008341.
VARIANT 497 497 R -> C (in dbSNP:rs370580423).
{ECO:0000269|PubMed:25469868}.
/FTId=VAR_072782.
CONFLICT 374 374 V -> M (in Ref. 1; AAA52153 and 2;
CAA30807). {ECO:0000305}.
TURN 41 43 {ECO:0000244|PDB:3TBG}.
HELIX 46 48 {ECO:0000244|PDB:3TBG}.
STRAND 51 53 {ECO:0000244|PDB:5TFT}.
HELIX 54 65 {ECO:0000244|PDB:3TBG}.
STRAND 67 73 {ECO:0000244|PDB:3TBG}.
STRAND 76 81 {ECO:0000244|PDB:3TBG}.
HELIX 83 91 {ECO:0000244|PDB:3TBG}.
TURN 92 94 {ECO:0000244|PDB:3TBG}.
HELIX 95 97 {ECO:0000244|PDB:3TBG}.
HELIX 105 110 {ECO:0000244|PDB:3TBG}.
STRAND 119 121 {ECO:0000244|PDB:4WNU}.
HELIX 126 141 {ECO:0000244|PDB:3TBG}.
STRAND 145 147 {ECO:0000244|PDB:4WNU}.
HELIX 148 165 {ECO:0000244|PDB:3TBG}.
TURN 166 169 {ECO:0000244|PDB:3TBG}.
HELIX 175 191 {ECO:0000244|PDB:3TBG}.
HELIX 200 214 {ECO:0000244|PDB:3TBG}.
HELIX 219 226 {ECO:0000244|PDB:3TBG}.
HELIX 228 232 {ECO:0000244|PDB:3TBG}.
HELIX 234 240 {ECO:0000244|PDB:3TBG}.
HELIX 242 261 {ECO:0000244|PDB:3TBG}.
HELIX 271 281 {ECO:0000244|PDB:3TBG}.
TURN 282 284 {ECO:0000244|PDB:3TBG}.
HELIX 292 323 {ECO:0000244|PDB:3TBG}.
HELIX 325 338 {ECO:0000244|PDB:3TBG}.
STRAND 341 343 {ECO:0000244|PDB:3TBG}.
HELIX 347 350 {ECO:0000244|PDB:3TBG}.
HELIX 354 367 {ECO:0000244|PDB:3TBG}.
STRAND 370 372 {ECO:0000244|PDB:3QM4}.
STRAND 382 384 {ECO:0000244|PDB:3TBG}.
STRAND 387 389 {ECO:0000244|PDB:3TBG}.
STRAND 394 397 {ECO:0000244|PDB:3TBG}.
HELIX 399 403 {ECO:0000244|PDB:3TBG}.
TURN 406 408 {ECO:0000244|PDB:3TBG}.
STRAND 409 411 {ECO:0000244|PDB:3TBG}.
HELIX 417 420 {ECO:0000244|PDB:3TBG}.
HELIX 439 441 {ECO:0000244|PDB:4WNV}.
HELIX 446 463 {ECO:0000244|PDB:3TBG}.
STRAND 464 467 {ECO:0000244|PDB:3TBG}.
STRAND 470 472 {ECO:0000244|PDB:4WNW}.
STRAND 479 487 {ECO:0000244|PDB:3TBG}.
STRAND 492 496 {ECO:0000244|PDB:3TBG}.
SEQUENCE 497 AA; 55769 MW; 542B1D505DF3CDAC CRC64;
MGLEALVPLA VIVAIFLLLV DLMHRRQRWA ARYPPGPLPL PGLGNLLHVD FQNTPYCFDQ
LRRRFGDVFS LQLAWTPVVV LNGLAAVREA LVTHGEDTAD RPPVPITQIL GFGPRSQGVF
LARYGPAWRE QRRFSVSTLR NLGLGKKSLE QWVTEEAACL CAAFANHSGR PFRPNGLLDK
AVSNVIASLT CGRRFEYDDP RFLRLLDLAQ EGLKEESGFL REVLNAVPVL LHIPALAGKV
LRFQKAFLTQ LDELLTEHRM TWDPAQPPRD LTEAFLAEME KAKGNPESSF NDENLRIVVA
DLFSAGMVTT STTLAWGLLL MILHPDVQRR VQQEIDDVIG QVRRPEMGDQ AHMPYTTAVI
HEVQRFGDIV PLGVTHMTSR DIEVQGFRIP KGTTLITNLS SVLKDEAVWE KPFRFHPEHF
LDAQGHFVKP EAFLPFSAGR RACLGEPLAR MELFLFFTSL LQHFSFSVPT GQPRPSHHGV
FAFLVSPSPY ELCAVPR


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