CYP4Z1

Summary

CYP4Z1 (cytochrome P450 family 4 subfamily Z member 1, HGNC:20583) is a protein-coding gene on chromosome 1p33, encoding Cytochrome P450 4Z1 (Q86W10). A cytochrome P450 monooxygenase that catalyzes the in-chain oxidation of fatty acids.

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 gene is part of a cluster of cytochrome P450 genes on chromosome 1p33.

Source: NCBI Gene 199974 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 54 total
• Druggable target: yes
• MANE Select transcript: NM_178134

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20583
Approved symbol	CYP4Z1
Name	cytochrome P450 family 4 subfamily Z member 1
Location	1p33
Locus type	gene with protein product
Status	Approved
Aliases	CYP4A20
Ensembl gene	ENSG00000186160
Ensembl biotype	protein_coding
OMIM	618953
Entrez	199974

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000334194, ENST00000471598

RefSeq mRNA: 1 — MANE Select: NM_178134 NM_178134

CCDS: CCDS545

Canonical transcript exons

ENST00000334194 — 12 exons

Exon	Start	End
ENSE00001332423	47117766	47118318
ENSE00001332451	47067231	47067667
ENSE00001610025	47106128	47106261
ENSE00001624288	47080623	47080667
ENSE00001649863	47099094	47099284
ENSE00001777832	47115529	47115593
ENSE00001779323	47068622	47068763
ENSE00001790093	47094566	47094669
ENSE00001797032	47082334	47082461
ENSE00001802520	47084620	47084744
ENSE00001803751	47084824	47084978
ENSE00003569691	47116650	47116732

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 79.53.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0595 / max 7.2051, expressed in 32 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2767	0.0345	27
201502	0.0250	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.53	gold quality
calcaneal tendon	UBERON:0003701	77.98	gold quality
tibial nerve	UBERON:0001323	72.25	gold quality
pancreatic ductal cell	CL:0002079	70.58	silver quality
bronchial epithelial cell	CL:0002328	68.94	gold quality
right lung	UBERON:0002167	68.58	gold quality
thoracic mammary gland	UBERON:0005200	68.58	gold quality
buccal mucosa cell	CL:0002336	68.45	silver quality
mammary gland	UBERON:0001911	68.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	67.72	gold quality
bronchus	UBERON:0002185	67.65	gold quality
right uterine tube	UBERON:0001302	67.59	gold quality
subcutaneous adipose tissue	UBERON:0002190	67.26	gold quality
epithelium of mammary gland	UBERON:0003244	66.40	gold quality
upper lobe of left lung	UBERON:0008952	66.38	gold quality
mammary duct	UBERON:0001765	66.17	gold quality
omental fat pad	UBERON:0010414	66.11	gold quality
mucosa of stomach	UBERON:0001199	66.04	gold quality
peritoneum	UBERON:0002358	66.04	gold quality
adipose tissue of abdominal region	UBERON:0007808	65.21	gold quality
upper lobe of lung	UBERON:0008948	65.19	gold quality
tendon	UBERON:0000043	64.21	gold quality
adipose tissue	UBERON:0001013	63.59	gold quality
tibialis anterior	UBERON:0001385	63.28	silver quality
Brodmann (1909) area 9	UBERON:0013540	62.84	gold quality
gastrocnemius	UBERON:0001388	62.54	gold quality
skin of abdomen	UBERON:0001416	62.45	gold quality
tibial artery	UBERON:0007610	62.38	gold quality
popliteal artery	UBERON:0002250	62.35	gold quality
muscle of leg	UBERON:0001383	62.30	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting CYP4Z1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-4693-5P	97.35	67.02	1234
HSA-LET-7D-3P	89.01	66.89	93

Literature-anchored findings (GeneRIF, showing 18)

• Human cytochrome P450 (CYP), termed CYP4Z1,was identified, and the cDNA was cloned from a breast carcinoma line . (PMID:15059886)
• PPARalpha has a role in CYP4X1 regulation, and the glucocorticoid and progesterone receptors have roles in CYP4Z1 gene activation (PMID:15797250)
• CYP4Z1-dependent in-chain hydroxylation of lauric and myristic acid, which in both cases leads to the formation of four different monohydroxylated products at positions omega-2, omega-3, omega-4, and omega-5, respectively (PMID:19090726)
• CYP4Z1, KIR and RDH10 could play a role in non-small-cell lung cancer progression (PMID:19473719)
• CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation (PMID:22841774)
• Our findings suggest that the CYP4Z2P- and CYP4Z1-3’UTR promote breast cancer angiogenesis collectively by activating the PI3K and ERK1/2 pathways through binding multiple miRNAs. (PMID:25701119)
• CYP4Z1 and CYP4Z2P were downregulated in MCF-7 cells compared with tamoxifen-resistant MCF-7-TamR cells (PMID:26980484)
• CYP4Z1 3’UTR could inhibit the migration and Epithelial-mesenchymal transition of breast cancer cells. (PMID:27520371)
• Data show that downregulation of cytochrome P450 family 4 CYP4Z1 or the pseudogene CYP4Z2P 3’-UTR promotes cell apoptosis. (PMID:28236635)
• This study reports on the creation of a new homology model of CYP4Z1 and performed molecular docking experiments, which indicate that all active substrates show a highly similar binding geometry compared to the endogenous substrates. (PMID:28951277)
• If CYP4Z1 has a role to play in modulating cancer progression, new data form yeast microsomes expressing recombinant human enzyme suggest that the mechanism does not involve direct 20-HETE generation by this enzyme. (PMID:29018033)
• Transcriptional factor six2 promotes the competitive endogenous RNA network between CYP4Z1 and pseudogene CYP4Z2P responsible for maintaining the stemness of breast cancer cells. (PMID:30832689)
• We recently demonstrated the presence of the human CYP4Z1 on the plasma membrane of MCF-7 breast cancer cells and the detection of high titers of anti-CYP4Z1 aAbs in breast cancer patients, but not in healthy controls. In the present study we show that cells of the normal breast cell line MCF-10A do not display CYP4Z1 on their surface. (PMID:31082724)
• Importance of asparagine-381 and arginine-487 for substrate recognition in CYP4Z1. (PMID:32044355)
• New Proluciferin Substrates for Human CYP4 Family Enzymes. (PMID:32869209)
• Profiling of CYP4Z1 and CYP1B1 expression in bladder cancers. (PMID:33692504)
• Cytochrome 4Z1 Expression Is Correlated with Poor Prognosis in Patients with Cervical Cancer. (PMID:34590601)
• Cytochrome 4Z1 Expression Connotes Unfavorable Prognosis in Ovarian Cancers. (PMID:36143940)

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp4t8	ENSDARG00000004964
danio_rerio	cyp4f3	ENSDARG00000053530
drosophila_melanogaster	Cyp4d1	FBGN0005670
drosophila_melanogaster	Cyp4d2	FBGN0011576
drosophila_melanogaster	Cyp4e2	FBGN0014469
drosophila_melanogaster	Cyp4c3	FBGN0015032
drosophila_melanogaster	Cyp4d8	FBGN0015033
drosophila_melanogaster	Cyp4e1	FBGN0015034
drosophila_melanogaster	Cyp4e3	FBGN0015035
drosophila_melanogaster	Cyp4ae1	FBGN0015036
drosophila_melanogaster	Cyp4p1	FBGN0015037
drosophila_melanogaster	Cyp4d14	FBGN0023541
drosophila_melanogaster	Cyp4s3	FBGN0030615
drosophila_melanogaster	Cyp4ac1	FBGN0031693
drosophila_melanogaster	Cyp4ac2	FBGN0031694
drosophila_melanogaster	Cyp4ac3	FBGN0031695
drosophila_melanogaster	Cyp4d21	FBGN0031925
drosophila_melanogaster	Cyp4ad1	FBGN0033292
drosophila_melanogaster	Cyp4p2	FBGN0033395
drosophila_melanogaster	Cyp4p3	FBGN0033397
drosophila_melanogaster	Cyp4aa1	FBGN0034053
drosophila_melanogaster	Cyp4d20	FBGN0035344
drosophila_melanogaster	Cyp312a1	FBGN0036778
caenorhabditis_elegans		WBGENE00007140
caenorhabditis_elegans		WBGENE00009226
caenorhabditis_elegans		WBGENE00010354
caenorhabditis_elegans		WBGENE00013381
caenorhabditis_elegans		WBGENE00016147
caenorhabditis_elegans		WBGENE00021200
caenorhabditis_elegans		WBGENE00021412

Paralogs (12): CYP19A1 (ENSG00000137869), CYP4B1 (ENSG00000142973), CYP4V2 (ENSG00000145476), CYP4A22 (ENSG00000162365), CYP4F11 (ENSG00000171903), CYP4F22 (ENSG00000171954), CYP4F2 (ENSG00000186115), CYP4F12 (ENSG00000186204), CYP4X1 (ENSG00000186377), CYP4F8 (ENSG00000186526), CYP4F3 (ENSG00000186529), CYP4A11 (ENSG00000187048)

Protein

Protein identifiers

Cytochrome P450 4Z1 — Q86W10 (reviewed: Q86W10)

Alternative names: CYPIVZ1, Laurate 7-monooxygenase

All UniProt accessions (1): Q86W10

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase that catalyzes the in-chain oxidation of fatty acids. Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates lauric and myristic acids predominantly at the omega-4 and omega-2 positions, respectively. Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA). Displays an absolute stereoselectivity in the epoxidation of arachidonic acid producing the 14(S),15(R)-epoxyeicosatrienoic acid (EET) enantiomer. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Preferentially detected in breast carcinoma tissue and mammary gland, whereas only marginal expression is found in all other tested tissues.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (1): NP_835235* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050196	Cytochrome_P450_Monoox	Family

Pfam: PF00067

Catalyzed reactions (Rhea), 11 shown:

• an organic molecule + reduced [NADPH–hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17149)
• dodecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 11-hydroxydodecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39751)
• dodecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 7-hydroxydodecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:45084)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH–hemoprotein reductase] + O2 = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:49856)
• dodecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 9-hydroxydodecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:66872)
• tetradecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 12-hydroxytetradecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:66876)
• tetradecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 10-hydroxytetradecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:66880)
• tetradecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 11-hydroxytetradecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:66884)
• dodecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 8-hydroxydodecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:66888)
• dodecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 10-hydroxydodecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:66892)
• tetradecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 9-hydroxytetradecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:66916)

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86W10-F1	92.00	0.82

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): 452 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 41 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_UNSATURATED_FATTY_ACID_METABOLIC_PROCESS, GOBP_ARACHIDONATE_METABOLIC_PROCESS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOBP_FATTY_ACID_METABOLIC_PROCESS, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_TETRAPYRROLE_BINDING, GOMF_IRON_ION_BINDING, GOMF_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, GOMF_ARACHIDONATE_MONOOXYGENASE_ACTIVITY, GOMF_MONOOXYGENASE_ACTIVITY

GO Biological Process (4): arachidonate metabolic process (GO:0019369), lauric acid metabolic process (GO:0048252), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (9): iron ion binding (GO:0005506), arachidonate 14,15-epoxygenase activity (GO:0008404), 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), fatty acid in-chain hydroxylase activity (GO:0052722), monooxygenase activity (GO:0004497), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monooxygenase activity	2
oxidoreductase activity	2
long-chain fatty acid metabolic process	1
icosanoid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
medium-chain fatty acid metabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
transition metal ion binding	1
arachidonate epoxygenase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
tetrapyrrole binding	1
catalytic activity	1
cation binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP4Z1	PPIG	Q13427	453
CYP4Z1	CYB5R3	P00387	424
CYP4Z1	ZNF835	Q9Y2P0	405
CYP4Z1	KIAA1755	Q5JYT7	399
CYP4Z1	RANBP3L	Q86VV4	395
CYP4Z1	HMGA1	P10910	383
CYP4Z1	CYB5R4	Q7L1T6	381
CYP4Z1	CYB5R1	Q9UHQ9	378
CYP4Z1	CYB5B	O43169	375
CYP4Z1	ZNF260	Q3ZCT1	348
CYP4Z1	FAM185A	Q8N0U4	308
CYP4Z1	DBX2	Q6ZNG2	305
CYP4Z1	FMO4	P31512	290
CYP4Z1	FMO1	Q01740	290
CYP4Z1	ZNF391	Q9UJN7	289

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2A974, F1Q8C3, H1A988, O18993, O35728, O88833, P00186, P04799, P08516, P08684, P13584, P14579, P14581, P15128, P15129, P20815, P20816, P20817, P24453, P24462, P24463, P24464, P33268, P33274, P51869, P51871, P78329, P79102, P79401, P98187, Q00557, Q08477, Q29496, Q3MID2, Q64391, Q64462, Q64464, Q6A152, Q6NT55, Q86W10

Diamond homologs: A0A067DE75, A0A067ELB0, A0A0B4L1W8, A0A0S2II38, A0A0U2U8U5, A0A140JWM8, A0A1I9Q5Z0, A0A3Q7HBJ5, A0A3Q7HS74, A0A517FND3, A0A5A4DV62, A0AAW1JA93, A0AAW1NEA3, A2A974, A2RRT9, A2Z212, A2ZHX7, A5BFI4, A9QNE7, B8AJL3, B8BJ22, F6H9N6, H2DH16, I1H7R8, I1TEM1, I7C6E8, I7CT85, K4CEE8, K4CI52, O46512, O55127, O81077, O88833, P08516, P0DXH8, P14579, P14581, P20816, P20817, P33274

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1716 predictions. Top by Δscore:

Variant	Effect	Δscore
1:47067664:GGAG:G	donor_gain	1.0000
1:47067665:GAGG:G	donor_gain	1.0000
1:47084822:A:AG	acceptor_gain	1.0000
1:47084823:G:GC	acceptor_gain	1.0000
1:47084823:GT:G	acceptor_gain	1.0000
1:47117754:T:A	acceptor_gain	1.0000
1:47067665:GAGGT:G	donor_loss	0.9900
1:47067668:G:C	donor_loss	0.9900
1:47067669:T:G	donor_loss	0.9900
1:47082330:T:G	acceptor_gain	0.9900
1:47082332:A:G	acceptor_gain	0.9900
1:47082458:GCTG:G	donor_gain	0.9900
1:47082459:CTGG:C	donor_loss	0.9900
1:47082460:TG:T	donor_loss	0.9900
1:47082461:GG:G	donor_loss	0.9900
1:47082463:TAAGA:T	donor_loss	0.9900
1:47084673:T:G	acceptor_gain	0.9900
1:47084817:A:AG	acceptor_gain	0.9900
1:47084819:TCCA:T	acceptor_loss	0.9900
1:47084820:CCA:C	acceptor_loss	0.9900
1:47084821:CAGTA:C	acceptor_loss	0.9900
1:47084822:A:AT	acceptor_loss	0.9900
1:47084823:G:A	acceptor_loss	0.9900
1:47084823:GTA:G	acceptor_gain	0.9900
1:47084823:GTAC:G	acceptor_gain	0.9900
1:47084823:GTACC:G	acceptor_gain	0.9900
1:47084974:CACAG:C	donor_loss	0.9900
1:47084975:ACAG:A	donor_loss	0.9900
1:47084976:CAGGT:C	donor_loss	0.9900
1:47084977:AG:A	donor_loss	0.9900

AlphaMissense

3392 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:47116668:T:C	F429L	0.991
1:47116670:C:A	F429L	0.991
1:47116670:C:G	F429L	0.991
1:47116716:T:C	F445L	0.990
1:47116718:C:A	F445L	0.990
1:47116718:C:G	F445L	0.990
1:47106180:C:A	R374S	0.988
1:47116653:T:C	F424L	0.988
1:47116655:T:A	F424L	0.988
1:47116655:T:G	F424L	0.988
1:47084915:T:C	F237L	0.984
1:47084917:C:A	F237L	0.984
1:47084917:C:G	F237L	0.984
1:47099239:G:C	R341P	0.984
1:47106172:A:T	E371V	0.983
1:47082379:G:C	R137P	0.982
1:47099237:C:G	C340W	0.982
1:47084626:T:A	W167R	0.980
1:47084626:T:C	W167R	0.980
1:47116654:T:C	F424S	0.980
1:47099228:G:C	Q337H	0.979
1:47099228:G:T	Q337H	0.979
1:47106162:T:C	C368R	0.979
1:47099235:T:C	C340R	0.978
1:47094584:G:C	R264P	0.977
1:47099190:T:A	W325R	0.976
1:47099190:T:C	W325R	0.976
1:47116707:T:C	F442L	0.976
1:47116709:C:A	F442L	0.976
1:47116709:C:G	F442L	0.976

dbSNP variants (sampled 300 via entrez): RS1000007975 (1:47074480 G>T), RS1000214376 (1:47060132 T>G), RS1000386369 (1:47079131 C>T), RS1000410521 (1:47054200 G>T), RS1000443346 (1:47078671 A>G,T), RS1000511617 (1:47110035 A>C), RS1000700602 (1:47093669 G>C), RS1001010134 (1:47104796 G>A,T), RS1001052871 (1:47086384 T>G), RS1001146612 (1:47062028 T>A,G), RS1001250999 (1:47062694 C>T), RS1001364082 (1:47089978 T>C), RS1001377075 (1:47089545 C>A,T), RS1001450136 (1:47055213 G>A), RS1001572680 (1:47084133 CT>C)

Disease associations

OMIM: gene MIM:618953 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90000014_1	Parkinson’s disease motor subtype (tremor dominant vs postural instability/gait difficulty)	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523375 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP4 family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 7c [PMID: 36414390]	Inhibition	7.38	pIC50
compound 7 [PMID: 32302132]	Inhibition	5.23	pIC50

ChEMBL bioactivities

23 potent at pChembl≥5 of 28 total, top 23 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.38	IC50	41.8	nM	CHEMBL5272822
7.20	IC50	63	nM	CHEMBL4800099
7.05	IC50	89.7	nM	CHEMBL5267609
7.00	IC50	100	nM	CHEMBL4564920
6.96	IC50	108.9	nM	CHEMBL5274921
6.70	IC50	200	nM	CHEMBL4557940
6.70	IC50	200	nM	CHEMBL4590991
6.52	IC50	300	nM	CHEMBL4435658
6.40	IC50	400	nM	CHEMBL4447108
6.30	IC50	500	nM	CHEMBL4466562
6.29	IC50	519.1	nM	CHEMBL5279945
6.22	IC50	600.9	nM	CHEMBL267865
6.16	IC50	700	nM	CHEMBL4568702
5.85	IC50	1400	nM	CHEMBL4554028
5.77	IC50	1700	nM	CHEMBL4442292
5.66	Ki	2200	nM	CHEMBL4557940
5.54	IC50	2900	nM	CHEMBL4564920
5.35	IC50	4500	nM	CHEMBL4590991
5.31	IC50	4900	nM	CHEMBL4447108
5.23	IC50	5900	nM	CHEMBL4557940
5.23	IC50	5900	nM	BENZYLIMIDAZOLE
5.17	IC50	6700	nM	BENZYLIMIDAZOLE
5.14	IC50	7200	nM	CHEMBL4435658

PubChem BioAssay actives

23 with measured affinity, of 127 total; 16 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
ethyl 4-[4-[(hydroxyamino)methylideneamino]phenyl]butanoate	1935286: Inhibition of CYP4Z1 in human HEK293T cells using Luciferin-BE as substrate incubated for 30 mins in presence of NADPH by luminescence based assay	ic50	0.0418	uM
3-[[(4-imidazol-1-ylbenzoyl)amino]methyl]benzoic acid	1732640: Inhibition of human CYP4Z1 overexpressed in human MCF7 cells using luciferin-3FBE as substrate incubated for 24 hrs followed by substrate addition by luminescence based assay	ic50	0.0630	uM
ethyl 2-[4-[(hydroxyamino)methylideneamino]phenyl]acetate	1935286: Inhibition of CYP4Z1 in human HEK293T cells using Luciferin-BE as substrate incubated for 30 mins in presence of NADPH by luminescence based assay	ic50	0.0897	uM
N-hexylbenzotriazol-1-amine	1607229: Inhibition of CYP4Z1 (unknown origin) in human HepG2 cell membranes transduced with lentiviral vector using luciferin-benzyl ether as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by P450-glo luciferase based luminescence assay	ic50	0.1000	uM
ethyl 5-[4-[(hydroxyamino)methylideneamino]phenyl]pentanoate	1935286: Inhibition of CYP4Z1 in human HEK293T cells using Luciferin-BE as substrate incubated for 30 mins in presence of NADPH by luminescence based assay	ic50	0.1089	uM
8-(benzotriazol-1-ylamino)octanoic acid	1607229: Inhibition of CYP4Z1 (unknown origin) in human HepG2 cell membranes transduced with lentiviral vector using luciferin-benzyl ether as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by P450-glo luciferase based luminescence assay	ic50	0.2000	uM
10-(benzotriazol-1-ylamino)decanoic acid	1607229: Inhibition of CYP4Z1 (unknown origin) in human HepG2 cell membranes transduced with lentiviral vector using luciferin-benzyl ether as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by P450-glo luciferase based luminescence assay	ic50	0.2000	uM
12-(benzotriazol-1-ylamino)dodecanoic acid	1607229: Inhibition of CYP4Z1 (unknown origin) in human HepG2 cell membranes transduced with lentiviral vector using luciferin-benzyl ether as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by P450-glo luciferase based luminescence assay	ic50	0.3000	uM
N-octylbenzotriazol-1-amine	1607229: Inhibition of CYP4Z1 (unknown origin) in human HepG2 cell membranes transduced with lentiviral vector using luciferin-benzyl ether as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by P450-glo luciferase based luminescence assay	ic50	0.4000	uM
N-decylbenzotriazol-1-amine	1607229: Inhibition of CYP4Z1 (unknown origin) in human HepG2 cell membranes transduced with lentiviral vector using luciferin-benzyl ether as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by P450-glo luciferase based luminescence assay	ic50	0.5000	uM
ethyl 3-[4-[(hydroxyamino)methylideneamino]phenyl]propanoate	1935286: Inhibition of CYP4Z1 in human HEK293T cells using Luciferin-BE as substrate incubated for 30 mins in presence of NADPH by luminescence based assay	ic50	0.5191	uM
N’-(4-butyl-2-methylphenyl)-N-hydroxymethanimidamide	1935286: Inhibition of CYP4Z1 in human HEK293T cells using Luciferin-BE as substrate incubated for 30 mins in presence of NADPH by luminescence based assay	ic50	0.6009	uM
N-butylbenzotriazol-1-amine	1607229: Inhibition of CYP4Z1 (unknown origin) in human HepG2 cell membranes transduced with lentiviral vector using luciferin-benzyl ether as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by P450-glo luciferase based luminescence assay	ic50	0.7000	uM
N-dodecylbenzotriazol-1-amine	1607229: Inhibition of CYP4Z1 (unknown origin) in human HepG2 cell membranes transduced with lentiviral vector using luciferin-benzyl ether as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by P450-glo luciferase based luminescence assay	ic50	1.4000	uM
6-(benzotriazol-1-ylamino)hexanoic acid	1607229: Inhibition of CYP4Z1 (unknown origin) in human HepG2 cell membranes transduced with lentiviral vector using luciferin-benzyl ether as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by P450-glo luciferase based luminescence assay	ic50	1.7000	uM
1-benzylimidazole	1732641: Inhibition of human CYP4Z1 overexpressed in human MCF7 cells using luciferin-BE as substrate incubated for 24 hrs followed by substrate addition by luminescence based assay	ic50	5.9000	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	increases expression	1
HET0016	decreases abundance, decreases reaction, increases abundance, increases expression	1
1-benzylimidazole	decreases stability, increases degradation, decreases reaction, decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
butylbenzyl phthalate	increases expression	1
lauric acid	decreases abundance, decreases reaction	1
20-hydroxy-5,8,11,14-eicosatetraenoic acid	increases abundance, decreases reaction	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases degradation, decreases reaction, decreases stability	1
CGP 52608	affects binding, increases reaction	1
U 0126	decreases reaction, increases expression	1
20-hydroxyeicosa-6(Z),15(Z)-dienoic acid	decreases reaction, increases expression, decreases response to substance	1
Resveratrol	affects cotreatment, decreases expression	1
Wortmannin	decreases reaction, increases expression	1
Copper	affects cotreatment, decreases expression	1
Dexamethasone	increases expression, decreases reaction	1
Diethylhexyl Phthalate	decreases expression	1
Hydralazine	increases expression, affects cotreatment	1
Latex	increases expression	1
Progesterone	decreases reaction, increases expression	1
Valproic Acid	increases expression, affects cotreatment	1
Mifepristone	increases expression, decreases reaction	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Myristic Acid	decreases abundance, decreases reaction	1

ChEMBL screening assays

36 unique, capped per target: 33 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4406418	Binding	Inhibition of CYP4Z1 (unknown origin) in human HepG2 cell membranes transduced with lentiviral vector using luciferin-benzyl ether as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by	Design and Characterization of the First Selective and Potent Mechanism-Based Inhibitor of Cytochrome P450 4Z1. — J Med Chem
CHEMBL5238689	ADMET	Inhibition of CYP4Z1 in human HEK293T cells using Luciferin-BE as substrate at 10 uM incubated for 30 mins in presence of NADPH by luminescence based assay relative to control	Identification of a Novel Potent CYP4Z1 Inhibitor Attenuating the Stemness of Breast Cancer Cells through Lead Optimization. — J Med Chem

Clinical trials (associated diseases)

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