CYP4F3

Summary

CYP4F3 (cytochrome P450 family 4 subfamily F member 3, HGNC:2646) is a protein-coding gene on chromosome 19p13.12, encoding Cytochrome P450 4F3 (Q08477). A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and their oxygenated derivatives (oxylipins).

This gene, CYP4F3, 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. The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F8, is approximately 18 kb away. Several transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 4051 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 124 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000896

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2646
Approved symbol	CYP4F3
Name	cytochrome P450 family 4 subfamily F member 3
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Aliases	CYP4F
Ensembl gene	ENSG00000186529
Ensembl biotype	protein_coding
OMIM	601270
Entrez	4051

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000221307, ENST00000585846, ENST00000586182, ENST00000587360, ENST00000588886, ENST00000591058, ENST00000592279, ENST00000592424, ENST00000609670, ENST00000865620, ENST00000865621, ENST00000865622, ENST00000865623, ENST00000948830

RefSeq mRNA: 4 — MANE Select: NM_000896 NM_000896, NM_001199208, NM_001199209, NM_001369696

CCDS: CCDS12332, CCDS59362

Canonical transcript exons

ENST00000221307 — 13 exons

Exon	Start	End
ENSE00000899780	15645719	15645863
ENSE00001513375	15659220	15662825
ENSE00001513388	15640897	15640945
ENSE00003491390	15658264	15658397
ENSE00003510545	15649160	15649281
ENSE00003539895	15641415	15641613
ENSE00003562101	15647052	15647105
ENSE00003584991	15658727	15658809
ENSE00003587401	15647197	15647324
ENSE00003594448	15649913	15650183
ENSE00003612987	15658491	15658555
ENSE00003638240	15652823	15652952
ENSE00003653290	15652569	15652635

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 98.34.

FANTOM5 (CAGE): breadth broad, TPM avg 3.8954 / max 1242.0788, expressed in 197 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174344	2.1646	95
174342	0.9400	97
174345	0.4802	33
174341	0.2905	42
174343	0.0200	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.34	gold quality
liver	UBERON:0002107	98.08	gold quality
trabecular bone tissue	UBERON:0002483	95.70	gold quality
blood	UBERON:0000178	93.95	gold quality
bone marrow	UBERON:0002371	93.89	gold quality
nephron tubule	UBERON:0001231	92.67	gold quality
bone marrow cell	CL:0002092	91.67	gold quality
lower esophagus mucosa	UBERON:0035834	89.43	gold quality
kidney epithelium	UBERON:0004819	89.02	gold quality
esophagus squamous epithelium	UBERON:0006920	88.36	gold quality
metanephric glomerulus	UBERON:0004736	87.57	gold quality
renal glomerulus	UBERON:0000074	87.47	gold quality
esophagus mucosa	UBERON:0002469	87.31	gold quality
jejunal mucosa	UBERON:0000399	86.55	gold quality
epithelium of esophagus	UBERON:0001976	86.30	gold quality
adult mammalian kidney	UBERON:0000082	86.07	gold quality
gall bladder	UBERON:0002110	85.81	gold quality
pancreatic ductal cell	CL:0002079	84.71	gold quality
duodenum	UBERON:0002114	83.51	gold quality
kidney	UBERON:0002113	81.54	gold quality
ileal mucosa	UBERON:0000331	80.98	gold quality
squamous epithelium	UBERON:0006914	80.93	silver quality
granulocyte	CL:0000094	80.60	gold quality
cortex of kidney	UBERON:0001225	78.83	gold quality
nasal cavity epithelium	UBERON:0005384	75.87	silver quality
small intestine Peyer’s patch	UBERON:0003454	75.23	gold quality
small intestine	UBERON:0002108	74.84	gold quality
islet of Langerhans	UBERON:0000006	74.47	gold quality
tongue squamous epithelium	UBERON:0006919	74.34	gold quality
spleen	UBERON:0002106	73.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	219.37
E-ANND-3	yes	16.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting CYP4F3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-548L	99.06	70.90	2560

Literature-anchored findings (GeneRIF, showing 13)

• identification of the distinct transcriptional features in myeloid, lymphoid, and hepatic cells that indicate the presence of multiple promoters in the CYP4F3 gene (PMID:12709424)
• CYP4F3A appears to be responsible for the leukotriene B(4) omega-hydroxylase activity (PMID:14715252)
• CYP4F18 is a critical protein in the regulation of LTB(4) metabolism (PMID:16380383)
• Results decribe the expression and physiological function of CYP4F3A and its subfamily in human eosinophils. (PMID:17980168)
• 3-hydroxystearate and 3-hydroxypalmitate are converted to omega-hydroxylated 3-OHDCA precursors in liver; CYP4F11 and, to a lesser extent, CYP4F2 catalyzed omega-hydroxylation of 3-hydroxystearate; CYP4F3b, CYP4F12, and CYP4A11 had negligible activity. (PMID:18065749)
• CYP4F3B is the key enzyme to produce 20-HETE by omega-hydroxylation of arachidonic acid in liver cells (PMID:18566475)
• Main fatty acid pathway is the omega-hydroxylation of polyunsaturated fatty acids. (PMID:18577768)
• By regulating the balance of LTB4 in the lung, LTB4OH may function as a suppressor of lung carcinogenesis. (PMID:19138970)
• can directly stimulate osteoclast differentiation dependent of RANKL (PMID:20047521)
• In this short review, emphasis will be placed on the regulation and the functional roles of human CYP4F3–{REVIEW} (PMID:22706230)
• Children who consumed a higher dietary ratio of omega6/omega3 were susceptible for Crohn’s disease if they were also carriers of specific variants of CYP4F3 and FADS2 genes. (PMID:24406470)
• The results suggest that a potentially functional single-nucleotide polymorphisms in CYP4F3 (rs4646904) may contribute to the etiology of lung cancer, especially in smokers. (PMID:28150878)
• High n3:n6 polyunsaturated fatty acids (PUFA) intake was associated with a reduced risk of ulcerative colitis (UC) in individuals with the GG/AG genotype at a single nucleotide polymorphism in CYP4F3 but not those with the AA genotype. The association between dietary n3:n6 PUFA intake and risk of UC may be modified variants at CYP4F3. (PMID:28991856)

Cross-species orthologs

32 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp4t8	ENSDARG00000004964
danio_rerio	cyp4f3	ENSDARG00000053530
mus_musculus	Cyp4f18	ENSMUSG00000003484
rattus_norvegicus	Cyp4f18	ENSRNOG00000015751
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), CYP4Z1 (ENSG00000186160), CYP4F12 (ENSG00000186204), CYP4X1 (ENSG00000186377), CYP4F8 (ENSG00000186526), CYP4A11 (ENSG00000187048)

Protein

Protein identifiers

Cytochrome P450 4F3 — Q08477 (reviewed: Q08477)

Alternative names: 20-hydroxyeicosatetraenoic acid synthase, CYPIVF3, Cytochrome P450-LTB-omega, Docosahexaenoic acid omega-hydroxylase CYP4F3, Leukotriene-B(4) 20-monooxygenase 2, Leukotriene-B(4) omega-hydroxylase 2

All UniProt accessions (3): Q08477, K7EJZ8, V9GYA1

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and their oxygenated derivatives (oxylipins). 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). May play a role in inactivation of pro-inflammatory and anti-inflammatory oxylipins during the resolution of inflammation. Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of oxylipins in myeloid cells, displaying higher affinity for arachidonate metabolite leukotriene B4 (LTB4). Inactivates LTB4 via three successive oxidative transformations to 20-hydroxy-LTB4, then to 20-oxo-LTB4 and to 20-carboxy-LTB4. Has omega-hydroxylase activity toward long-chain fatty acid epoxides with preference for 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate (EET) and 9,10-epoxyoctadecanoate. Omega-hydroxylates monohydroxy polyunsaturated fatty acids (PUFAs), including hydroxyeicosatetraenoates (HETEs) and hydroxyeicosapentaenoates (HEPEs), to dihydroxy compounds. Contributes to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid, by catalyzing successive omega-oxidations to the corresponding dicarboxylic acid, thereby initiating chain shortening. Has low hydroxylase activity toward PUFAs. Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of polyunsaturated fatty acids (PUFAs). Participates in the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure. Has high omega-hydroxylase activity toward other PUFAs, including eicosatrienoic acid (ETA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Can also catalyze the oxidation of the penultimate carbon (omega-1 oxidation) of PUFAs with lower efficiency. Contributes to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid and hexacosanoic acid, by catalyzing successive omega-oxidations to the corresponding dicarboxylic acids, thereby initiating chain shortening. Omega-hydroxylates long-chain 3-hydroxy fatty acids, likely initiating the oxidative conversion to the corresponding 3-hydroxydicarboxylic fatty acids. Has omega-hydroxylase activity toward long-chain fatty acid epoxides with preference for 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate (EET) and 9,10-epoxyoctadecanoate.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Selectively expressed in blood neutrophils and bone marrow cells. Coexpressed with CYP4F3B in prostate, ileum and trachea. Selectively expressed in liver and kidney. It is also the predominant CYP4F isoform in trachea and tissues of the gastrointestinal tract.

Activity regulation. Inhibited by carbon monoxide (CO).

Pathway. Lipid metabolism; leukotriene B4 degradation. Lipid metabolism; arachidonate metabolism.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q08477-1	CYP4F3A	yes
Q08477-2	CYP4F3B

RefSeq proteins (4): NP_000887, NP_001186137, NP_001186138, NP_001356625 (=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

Enzyme classification (BRENDA):

• EC 1.14.14.79 — docosahexaenoic acid omega-hydroxylase (BRENDA: 1 organisms, 8 substrates, 13 inhibitors, 0 Km, 0 kcat entries)
• EC 1.14.14.94 — leukotriene-B4 20-monooxygenase (BRENDA: 4 organisms, 65 substrates, 15 inhibitors, 41 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

15 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
LEUKOTRIENE B4	0.0002–0.868	15
6-TRANS-LEUKOTRIENE B4	0.0556–0.0961	3
Z12(13)-EPOXYOCTADEC-Z9-ENOIC ACID	0.0618–0.135	3
Z9(10)-EPOXYOCTADEC-Z12-ENOIC ACID	0.0466–0.1631	3
Z9(10)-EPOXYOCTADECANOIC ACID	0.0063–0.0357	3
12-HYDROXY-5,8,10,14-EICOSATETRAENOIC ACID	0.0142–0.0752	2
12-HYDROXYSTEARATE	0.0409–0.0423	2
LIPOXIN A4	0.0582–0.254	2
NADPH	0.0008–0.001	2
20-HYDROXY-LEUKOTRIENE B4	0.0065	1
5-DEOXY-LEUKOTRIENE B4	0.0056	1
5-EPI-LEUKOTRIENE B4	0.0066	1
6-TRANS-12-EPI-LEUKOTRIENE B4	0.0038	1
LIPOXIN B4	0.0179	1
PROSTAGLANDIN A1	0.04	1

Catalyzed reactions (Rhea), 12 shown:

• an organic molecule + reduced [NADPH–hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17149)
• leukotriene B4 + reduced [NADPH–hemoprotein reductase] + O2 = 20-hydroxy-leukotriene B4 + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:22176)
• 22-oxodocosanoate + reduced [NADPH–hemoprotein reductase] + O2 = docosanedioate + oxidized [NADPH–hemoprotein reductase] + H2O + 2 H(+) (RHEA:39043)
• 26-oxohexacosanoate + reduced [NADPH–hemoprotein reductase] + O2 = hexacosanedioate + oxidized [NADPH–hemoprotein reductase] + H2O + 2 H(+) (RHEA:39047)
• 22-hydroxydocosanoate + reduced [NADPH–hemoprotein reductase] + O2 = 22-oxodocosanoate + oxidized [NADPH–hemoprotein reductase] + 2 H2O + H(+) (RHEA:39055)
• 26-hydroxyhexacosanoate + reduced [NADPH–hemoprotein reductase] + O2 = 26-oxohexacosanoate + oxidized [NADPH–hemoprotein reductase] + 2 H2O + H(+) (RHEA:39059)
• tetracosanoate + reduced [NADPH–hemoprotein reductase] + O2 = 24-hydroxytetracosanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39719)
• 3-hydroxyhexadecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 3,16-dihydroxyhexadecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39731)
• 3-hydroxyoctadecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 3,18-dihydroxyoctadecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39735)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH–hemoprotein reductase] + O2 = 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39755)
• (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 19-hydroxy-(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39787)
• (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 20-hydroxy-(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39791)

UniProt features (13 total): sequence variant 5, sequence conflict 3, binding site 2, chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08477-F1	92.04	0.80

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 (2): 328 (covalent); 468 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-211935	Fatty acids
R-HSA-211958	Miscellaneous substrates
R-HSA-211979	Eicosanoids
R-HSA-2142691	Synthesis of Leukotrienes (LT) and Eoxins (EX)

MSigDB gene sets: 197 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, REACTOME_BIOLOGICAL_OXIDATIONS, 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_KETONE_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, HSIAO_LIVER_SPECIFIC_GENES, CAIRO_HEPATOBLASTOMA_DN, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS

GO Biological Process (12): icosanoid metabolic process (GO:0006690), leukotriene metabolic process (GO:0006691), fatty acid omega-oxidation (GO:0010430), arachidonate metabolic process (GO:0019369), leukotriene B4 catabolic process (GO:0036101), menaquinone catabolic process (GO:0042361), phylloquinone catabolic process (GO:0042376), omega-hydroxylase P450 pathway (GO:0097267), lipoxin A4 metabolic process (GO:2001302), lipoxin B4 metabolic process (GO:2001304), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (14): monooxygenase activity (GO:0004497), iron ion binding (GO:0005506), heme binding (GO:0020037), leukotriene-B4 20-monooxygenase activity (GO:0050051), arachidonate omega-hydroxylase activity (GO:0052869), 20-hydroxy-leukotriene B4 omega oxidase activity (GO:0097258), 20-aldehyde-leukotriene B4 20-monooxygenase activity (GO:0097259), long-chain fatty acid omega-hydroxylase activity (GO:0102033), long-chain fatty acid omega-1 hydroxylase activity (GO:0120319), very long-chain fatty acid omega-hydroxylase activity (GO:0140692), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), 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), metal ion binding (GO:0046872)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cytochrome P450 - arranged by substrate type	3
Arachidonate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
long-chain fatty acid metabolic process	3
unsaturated fatty acid metabolic process	3
monooxygenase activity	3
icosanoid metabolic process	2
fatty acid derivative metabolic process	2
oxidoreductase activity	2
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	2
fatty acid omega-hydroxylase activity	2
carboxylic acid metabolic process	1
fatty acid oxidation	1
olefinic compound metabolic process	1
leukotriene catabolic process	1
leukotriene B4 metabolic process	1
long-chain fatty acid catabolic process	1
icosanoid catabolic process	1
menaquinone metabolic process	1
ketone catabolic process	1
vitamin K catabolic process	1
arachidonate metabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
transition metal ion binding	1
tetrapyrrole binding	1
leukotriene B4 catabolic process	1
oxidoreductase activity, acting on CH-OH group of donors	1
fatty acid omega-1 hydroxylase activity	1
catalytic activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	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

1760 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP4F3	PPIG	Q13427	731
CYP4F3	NIPAL4	Q0D2K0	611
CYP4F3	CYP2J2	P51589	587
CYP4F3	CYB5B	O43169	576
CYP4F3	EPHX2	P34913	571
CYP4F3	CYB5A	P00167	570
CYP4F3	POR	P16435	523
CYP4F3	GPR75	O95800	522
CYP4F3	UGT1A10	Q9HAW8	474
CYP4F3	PTGS2	P35354	473
CYP4F3	UGT1A6	P19224	469
CYP4F3	UGT1A7	Q9HAW7	469
CYP4F3	UGT1A4	P22310	457
CYP4F3	UGT1A8	Q9HAW9	454
CYP4F3	UGT1A1	P22309	440

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CYP4F3	PDS5B	psi-mi:“MI:0915”(physical association)	0.400
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
TM4SF20	CD74	psi-mi:“MI:0914”(association)	0.350
pyrG	CYP4F3	psi-mi:“MI:0915”(physical association)	0.000
CYP4F3		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): PDS5B (Proximity Label-MS), CYP4F3 (Affinity Capture-MS), CYP4F3 (Affinity Capture-RNA), CYP4F3 (Affinity Capture-MS), CYP4F3 (Two-hybrid)

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: A0A067DT54, A0A067E1K2, A0A0S2II38, A0A140JWM8, A0A1B4XBH8, A0A1W5T1Y6, A0A3Q7HBJ5, A0A517FNB9, A0A517FNC6, A0A5B8ND22, A0A9Y1LLN2, A0AAW1NEA3, A2QTE8, A2RRT9, A2Z212, A9QNE7, B0XZV0, B1NF18, B5BSX1, B6SSW8, B8AJL3, B8AV52, B8QHP1, B8QHP5, B9X287, F1SY66, G3XMC3, I1GQE7, K4CI52, L7T720, L7T8H2, O23051, O35728, O49858, O61387, O81077, O88833, P08682, P0DXH4, P14137

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1903 predictions. Top by Δscore:

Variant	Effect	Δscore
19:15649278:AGGA:A	donor_gain	1.0000
19:15649279:GGA:G	donor_gain	1.0000
19:15649279:GGAG:G	donor_gain	1.0000
19:15649280:GA:G	donor_gain	1.0000
19:15649280:GAG:G	donor_gain	1.0000
19:15649282:G:GG	donor_gain	1.0000
19:15649909:GCA:G	acceptor_loss	1.0000
19:15649910:CAGG:C	acceptor_loss	1.0000
19:15649911:A:AG	acceptor_gain	1.0000
19:15649911:AG:A	acceptor_gain	1.0000
19:15649912:G:GA	acceptor_gain	1.0000
19:15649912:GG:G	acceptor_gain	1.0000
19:15649912:GGAA:G	acceptor_gain	1.0000
19:15650180:CAAGG:C	donor_loss	1.0000
19:15650181:AAGG:A	donor_loss	1.0000
19:15650182:AGGT:A	donor_loss	1.0000
19:15650184:GTG:G	donor_loss	1.0000
19:15652949:AATGG:A	donor_loss	1.0000
19:15652951:TGGTG:T	donor_loss	1.0000
19:15652952:GGTG:G	donor_loss	1.0000
19:15652953:G:A	donor_loss	1.0000
19:15652954:T:TC	donor_loss	1.0000
19:15652955:G:GC	donor_loss	1.0000
19:15652956:AGTG:A	donor_loss	1.0000
19:15641612:TGG:T	donor_loss	0.9900
19:15641613:GGTG:G	donor_loss	0.9900
19:15641614:GTGAG:G	donor_loss	0.9900
19:15641615:T:TC	donor_loss	0.9900
19:15641616:G:GT	donor_loss	0.9900
19:15641617:A:AC	donor_loss	0.9900

AlphaMissense

3433 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:15658793:T:C	F461L	0.993
19:15658795:C:A	F461L	0.993
19:15658795:C:G	F461L	0.993
19:15658310:A:C	S388R	0.990
19:15658312:C:A	S388R	0.990
19:15658312:C:G	S388R	0.990
19:15659226:C:G	C468W	0.989
19:15647242:G:C	R148P	0.986
19:15658317:G:C	R390T	0.986
19:15658745:T:C	F445L	0.986
19:15658747:T:A	F445L	0.986
19:15658747:T:G	F445L	0.986
19:15647262:T:C	F155L	0.984
19:15647264:C:A	F155L	0.984
19:15647264:C:G	F155L	0.984
19:15647241:C:A	R148S	0.983
19:15647229:T:A	W144R	0.982
19:15647229:T:C	W144R	0.982
19:15658318:G:C	R390S	0.982
19:15658318:G:T	R390S	0.982
19:15659231:G:A	G470E	0.982
19:15649166:T:A	W178R	0.981
19:15649166:T:C	W178R	0.981
19:15658784:T:C	F458L	0.981
19:15658786:T:A	F458L	0.981
19:15658786:T:G	F458L	0.981
19:15652852:T:A	W339R	0.979
19:15652852:T:C	W339R	0.979
19:15658541:T:A	W434R	0.979
19:15658541:T:C	W434R	0.979

dbSNP variants (sampled 300 via entrez): RS1000128213 (19:15650587 T>A), RS1000149432 (19:15643889 C>A,T), RS1000241751 (19:15645724 C>T), RS1000384642 (19:15640216 G>A), RS1000438526 (19:15640429 A>G), RS1000725308 (19:15641299 C>T), RS1000764541 (19:15639268 G>A), RS1000879941 (19:15656544 A>G), RS1001190903 (19:15639643 C>T), RS1001249959 (19:15656279 A>G), RS1001335759 (19:15644522 G>A,T), RS1001347738 (19:15655862 A>G), RS1001380337 (19:15656184 C>G,T), RS1001609742 (19:15639821 G>A), RS1001734118 (19:15644685 G>C)

Disease associations

OMIM: gene MIM:601270 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3508692 (SINGLE PROTEIN), CHEMBL4523986 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 15,540 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL477772	PAZOPANIB	4	15,540

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
HET0016	Inhibition	7.0	pIC50

ChEMBL bioactivities

16 potent at pChembl≥5 of 17 total, top 16 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.60	IC50	251.2	nM	CHEMBL601428
6.16	IC50	700	nM	CHEMBL3330409
6.05	IC50	900	nM	CHEMBL3330410
5.96	IC50	1100	nM	CHEMBL2130955
5.72	IC50	1900	nM	CHEMBL2130955
5.60	IC50	2500	nM	CHEMBL5612347
5.55	IC50	2800	nM	CHEMBL2130955
5.43	IC50	3700	nM	CHEMBL5406721
5.43	IC50	3700	nM	CHEMBL46909
5.42	IC50	3800	nM	CHEMBL5418617
5.41	IC50	3900	nM	CHEMBL5429178
5.31	IC50	4900	nM	CHEMBL2130955
5.23	IC50	5900	nM	CHEMBL5406218
5.22	IC50	6053	nM	CHEMBL65590
5.10	IC50	7900	nM	PAZOPANIB
5.00	IC50	1e+04	nM	CHEMBL5395150

PubChem BioAssay actives

18 with measured affinity, of 504 total; 15 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
8-imidazol-1-yl-5,6,7,8-tetrahydroquinoline	2022035: Inhibition of CYP450 (unknown origin)	ic50	0.0335	uM
N-(4-chlorophenyl)-5-ethyl-N-methyl-3-phenyl-1,2-oxazole-4-carboxamide	2108148: Inhibition of CYP450 (unknown origin)	ic50	0.2512	uM
2-(dimethylamino)-2-(2-ethylphenyl)-N-[3-(3-sulfamoylphenyl)-1H-indazol-5-yl]acetamide	2119433: Inhibition of CYP450 (unknown origin)	ic50	0.7000	uM
2-pyrrolidin-1-yl-N-[3-(3-sulfamoylphenyl)-1H-indazol-5-yl]-2-thiophen-3-ylacetamide	2119433: Inhibition of CYP450 (unknown origin)	ic50	0.9000	uM
2-[4-(trifluoromethyl)phenyl]chromen-4-one	1860369: Inhibition of CYP450 in human HCT-116 cells assessed as 20-HETE formation in presence of arachidonic acid incubated for 15 mins by multi-enzyme assay based LC-MS/MS analysis	ic50	1.1000	uM
4-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]-4-N-[[(7R)-5,6,7,8-tetrahydro-1,6-naphthyridin-7-yl]methyl]cyclohexane-1,4-diamine	2124397: Inhibition of CYP450 (unknown origin)	ic50	2.5000	uM
1-[3-(2,4-dimethoxyphenyl)phenyl]-2,4-dimethoxybenzene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.7000	uM
1-[(E)-2-(2,4-dimethoxyphenyl)ethenyl]-3,5-dimethoxybenzene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.7000	uM
2,4-bis(3,5-dimethoxyphenyl)pyrimidine	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.8000	uM
2,5-bis(3,5-dimethoxyphenyl)thiophene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.9000	uM
4-[2-(2,4-dimethoxyphenyl)-1,3-thiazol-4-yl]phenol	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	5.9000	uM
1-pyridin-4-yl-1a,2,3,7b-tetrahydro-1H-cyclopropa[a]naphthalen-4-ol	2022025: Inhibition of CYP450 in human liver microsomes	ic50	6.0534	uM
(5R)-3-[1-(1H-indol-2-ylmethyl)piperidin-4-yl]-5-(6-methoxyquinolin-4-yl)-1,3-oxazolidin-2-one	306257: Inhibition of CYP450	ic50	7.9433	uM
3-[1-[(3,4-dimethylphenyl)methyl]piperidin-4-yl]-5-(6-methoxyquinolin-4-yl)-1,3-oxazolidin-2-one	306257: Inhibition of CYP450	ic50	10.0000	uM
1-[3-(3,5-dimethoxyphenyl)phenyl]-3,5-dimethoxybenzene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	10.0000	uM

CTD chemical–gene interactions

62 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Tretinoin	increases expression	4
deoxynivalenol	affects cotreatment, decreases expression, increases expression	2
sulforaphane	increases expression	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Formaldehyde	decreases expression, increases expression	2
Zearalenone	affects cotreatment, decreases expression, increases expression	2
Asbestos, Crocidolite	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Phenol	increases expression	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
rubiarbonone C	decreases activity, decreases reaction, increases hydroxylation	1
urushiol	decreases expression	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
senkirkine	decreases expression	1
heliotrine	decreases expression	1
3,4-dichloroaniline	increases expression	1
beta-lapachone	increases expression	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
19-hydroxy-5,8,11,14-eicosatetraenoic acid	increases chemical synthesis	1
20-hydroxy-5,8,11,14-eicosatetraenoic acid	increases chemical synthesis	1
diethyl malate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
obeticholic acid	decreases expression	1
abrine	decreases expression	1
apple polyphenol extract	increases expression	1

ChEMBL screening assays

204 unique, capped per target: 202 admet, 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3509253	ADMET	Enzyme kinetics constant (Km value) for CYP4F3B was determined in human liver microsome incubated with [14C]SPP100 hemifumarate	FDA drug approval package for Aliskiren hemifumarate
CHEMBL4614611	Binding	Drug metabolism in human liver microsomes assessed as Cytochrome P450-mediated formation of 12-OHNVP by measuring Kcat/Km ratio in presence of NADPH regenerating reagents by uHPLC-MS/MS analysis	Twelfth-Position Deuteration of Nevirapine Reduces 12-Hydroxy-Nevirapine Formation and Nevirapine-Induced Hepatocyte Death. — J Med Chem

Clinical trials (associated diseases)

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