CYP2D7

Summary

CYP2D7 (cytochrome P450 family 2 subfamily D member 7 (gene/pseudogene), HGNC:2624) is a protein-coding gene on chromosome 22q13.2, encoding Cytochrome P450 2D7 (A0A087X1C5). May be responsible for the metabolism of many drugs and environmental chemicals that it oxidizes.

This gene is a member of the cytochrome P450 gene superfamily. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This gene is a segregating pseudogene, where some individuals may have an allele that encodes a functional enzyme, while other individuals have an allele encoding a protein that is predicted to be non-functional. In this case, the functional allele is thought to be rare. This locus is part of a cluster of cytochrome P450 genes on chromosome 22.

Source: NCBI Gene 1564 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 1 total
• Druggable target: yes

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2624
Approved symbol	CYP2D7
Name	cytochrome P450 family 2 subfamily D member 7 (gene/pseudogene)
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205702
Ensembl biotype	protein_coding
Entrez	1564

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding_CDS_not_defined, 3 retained_intron, 2 protein_coding_LoF

ENST00000358097, ENST00000424775, ENST00000433992, ENST00000435101, ENST00000435688, ENST00000610593, ENST00000651010, ENST00000711577

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000358097 — 9 exons

Exon	Start	End
ENSE00003988857	42142728	42142880
ENSE00003988859	42143410	42143581
ENSE00003988860	42140203	42140456
ENSE00003988861	42141534	42141675
ENSE00003988862	42140555	42140696
ENSE00003988863	42141868	42142044
ENSE00003988864	42141152	42141339
ENSE00003988867	42144284	42144549
ENSE00003988868	42142479	42142639

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 98.15.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0385 / max 23.0015, expressed in 10 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194411	0.0385	10
194412	0.0162	3
209490	0.0094	3

Top tissues by expression

132 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.15	gold quality
liver	UBERON:0002107	95.50	gold quality
lower esophagus mucosa	UBERON:0035834	84.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.79	gold quality
pituitary gland	UBERON:0000007	80.36	gold quality
adenohypophysis	UBERON:0002196	79.54	gold quality
cerebellar hemisphere	UBERON:0002245	79.38	gold quality
cerebellar cortex	UBERON:0002129	79.30	gold quality
cerebellum	UBERON:0002037	79.26	gold quality
granulocyte	CL:0000094	78.59	gold quality
right frontal lobe	UBERON:0002810	78.58	gold quality
right lobe of thyroid gland	UBERON:0001119	77.47	gold quality
left lobe of thyroid gland	UBERON:0001120	77.47	gold quality
mucosa of transverse colon	UBERON:0004991	77.39	gold quality
nucleus accumbens	UBERON:0001882	77.28	gold quality
thyroid gland	UBERON:0002046	77.18	gold quality
blood	UBERON:0000178	76.91	gold quality
anterior cingulate cortex	UBERON:0009835	76.77	gold quality
metanephros cortex	UBERON:0010533	76.52	gold quality
right uterine tube	UBERON:0001302	76.49	gold quality
Ammon’s horn	UBERON:0001954	76.20	gold quality
hypothalamus	UBERON:0001898	75.85	gold quality
putamen	UBERON:0001874	75.64	gold quality
cortical plate	UBERON:0005343	75.45	gold quality
esophagus mucosa	UBERON:0002469	75.38	gold quality
brain	UBERON:0000955	75.30	gold quality
amygdala	UBERON:0001876	75.23	gold quality
temporal lobe	UBERON:0001871	75.22	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.19	gold quality
substantia nigra	UBERON:0002038	75.07	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-7	yes	5.95
E-ENAD-21	yes	5.95
E-ANND-3	no	1.29

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• The loss of the stop codon in CYP2D7 does not result in the generation of enzymatically active protein in human liver. (PMID:30040020)
• Association Between CYP2D7 and TCF20 Polymorphisms and Coronary Heart Disease. (PMID:39060884)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Cytochrome P450 2D7 — A0A087X1C5 (reviewed: A0A087X1C5)

All UniProt accessions (0):

UniProt curated annotations — full annotation on UniProt →

Function. May be responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It may be involved in the metabolism of codeine to morphine. However, another study could not confirm it.

Subcellular location. Membrane. Cytoplasm. Mitochondrion.

Tissue specificity. Expressed in brain cortex (at protein level).

Polymorphism. One study shows that a rare double polymorphism allows the expression of a functional protein. Two subsequent studies could not confirm the combined existence of both polymorphisms in the genomes examined in those studies.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (0): (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR008069	Cyt_P450_E_grp-I_CYP2D-like	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050182	Cytochrome_P450_fam2	Family

Pfam: PF00067

Catalyzed reactions (Rhea), 1 shown:

• an organic molecule + reduced [NADPH–hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17149)

UniProt features (14 total): sequence variant 6, topological domain 3, transmembrane region 2, chain 1, binding site 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A087X1C5-F1	91.33	0.76

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 461 (axial binding residue)

Glycosylation sites (1): 416

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 3 (showing top): chr22q13, DESCARTES_MAIN_FETAL_PAEP_MECOM_POSITIVE_CELLS, KAYO_CALORIE_RESTRICTION_MUSCLE_DN

GO Biological Process (3): xenobiotic metabolic process (GO:0006805), arachidonate metabolic process (GO:0019369), xenobiotic catabolic process (GO:0042178)

GO Molecular Function (4): iron ion binding (GO:0005506), 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 (GO:0016712), heme binding (GO:0020037), aromatase activity (GO:0070330)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
metabolic process	1
cellular response to xenobiotic stimulus	1
long-chain fatty acid metabolic process	1
icosanoid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
xenobiotic metabolic process	1
catabolic process	1
transition metal ion binding	1
monooxygenase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
tetrapyrrole binding	1
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	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A087X1C5, E9Q816, O18992, O46658, P00191, P03940, P08686, P10633, P10634, P10635, P11714, P12394, P12938, P12939, P15540, P24456, P24457, P30437, P51589, P51590, P52786, P70085, P78329, Q01361, Q0IIF9, Q29473, Q29488, Q2LA59, Q2LA60, Q2LCM1, Q2XNC8, Q2XNC9, Q4V8D1, Q64403, Q64562, Q64680, Q6GUQ4, Q6VVW9, Q6VVX0, Q7Z449

Diamond homologs: A0A087X1C5, E9Q5K4, F1Q8C3, O18809, O18992, O35293, O46658, O54749, O54750, O55071, O62671, O93297, P00176, P00178, P00179, P00180, P00181, P00182, P04167, P05178, P05179, P05180, P05181, P08682, P08683, P10610, P10632, P10633, P10634, P10635, P11371, P11712, P11714, P12789, P12790, P12791, P12938, P12939, P15123, P17666

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1322 predictions. Top by Δscore:

Variant	Effect	Δscore
22:42140453:CGGC:C	acceptor_gain	1.0000
22:42140454:GGC:G	acceptor_gain	1.0000
22:42140454:GGCC:G	acceptor_loss	1.0000
22:42140457:C:CA	acceptor_loss	1.0000
22:42140457:C:CC	acceptor_gain	1.0000
22:42140458:T:C	acceptor_loss	1.0000
22:42140550:GGCAC:G	donor_loss	1.0000
22:42140551:GCAC:G	donor_loss	1.0000
22:42140552:CACCT:C	donor_loss	1.0000
22:42140553:A:C	donor_loss	1.0000
22:42140554:CC:C	donor_loss	1.0000
22:42140554:CCTG:C	donor_gain	1.0000
22:42140578:T:TA	donor_gain	1.0000
22:42140695:CC:C	acceptor_gain	1.0000
22:42140695:CCCTG:C	acceptor_loss	1.0000
22:42140696:CC:C	acceptor_gain	1.0000
22:42140697:C:A	acceptor_loss	1.0000
22:42140697:C:CC	acceptor_gain	1.0000
22:42140697:C:T	acceptor_gain	1.0000
22:42140698:T:A	acceptor_loss	1.0000
22:42140702:C:CT	acceptor_gain	1.0000
22:42141146:GCCTA:G	donor_loss	1.0000
22:42141147:CCTAC:C	donor_loss	1.0000
22:42141148:CTAC:C	donor_loss	1.0000
22:42141149:TA:T	donor_loss	1.0000
22:42141150:ACCT:A	donor_loss	1.0000
22:42141177:T:TA	donor_gain	1.0000
22:42141533:CG:C	donor_gain	1.0000
22:42141865:CACCT:C	donor_loss	1.0000
22:42141866:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000808015 (22:42144518 A>C), RS1000872552 (22:42145931 T>C), RS1001741514 (22:42140461 G>C), RS1002710169 (22:42139563 A>G), RS1002776122 (22:42143022 C>A,T), RS1002944570 (22:42139732 G>C), RS1002988125 (22:42142956 C>A,T), RS1003581812 (22:42142304 C>T), RS1003595425 (22:42145917 G>T), RS1004538564 (22:42143144 C>A,G,T), RS1005722311 (22:42139080 T>C), RS1005827768 (22:42146244 C>G), RS1006417480 (22:42145120 C>A), RS1006552346 (22:42141845 CCCA>C), RS1007553893 (22:42141278 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004364_23	Intelligence	3.000000e-10
GCST004364_5	Intelligence	3.000000e-10
GCST004521_160	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_244	Autism spectrum disorder or schizophrenia	4.000000e-09
GCST005316_267	Intelligence (MTAG)	2.000000e-09
GCST006269_606	General cognitive ability	3.000000e-13
GCST006803_13	Schizophrenia	2.000000e-14
GCST008595_232	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-15
GCST009212_17	Isthmus-cingulate cortex volume	2.000000e-06
GCST010002_83	Refractive error	2.000000e-27

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3542437 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs530303678	CYP2D7		0.00	0

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
benazol P	affects expression	1
fipronil	increases expression	1
deguelin	decreases expression	1
picoxystrobin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Valproic Acid	increases methylation	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.