CYP4F8

Summary

CYP4F8 (cytochrome P450 family 4 subfamily F member 8, HGNC:2648) is a protein-coding gene on chromosome 19p13.12, encoding Cytochrome P450 4F8 (P98187). A cytochrome P450 monooxygenase involved in the metabolism of endogenous polyunsaturated fatty acids (PUFAs) and their oxygenated derivatives (oxylipins).

This gene, CYP4F8, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and functions as a 19-hydroxylase of prostaglandins in seminal vesicles. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F3, is approximately 18 kb away.

Source: NCBI Gene 11283 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 60 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007253

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2648
Approved symbol	CYP4F8
Name	cytochrome P450 family 4 subfamily F member 8
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000186526
Ensembl biotype	protein_coding
OMIM	611545
Entrez	11283

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 retained_intron, 3 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000325723, ENST00000441682, ENST00000585349, ENST00000587680, ENST00000589722, ENST00000589778, ENST00000589927, ENST00000590209, ENST00000590745, ENST00000612078, ENST00000617645, ENST00000622291

RefSeq mRNA: 1 — MANE Select: NM_007253 NM_007253

CCDS: CCDS74303

Canonical transcript exons

ENST00000612078 — 13 exons

Exon	Start	End
ENSE00001113237	15629193	15630639
ENSE00001247965	15619635	15619762
ENSE00001528516	15615218	15615280
ENSE00003535297	15623699	15623765
ENSE00003545901	15628531	15628595
ENSE00003601391	15628302	15628435
ENSE00003613597	15628761	15628843
ENSE00003619060	15619490	15619543
ENSE00003683427	15623965	15624094
ENSE00003712741	15615616	15615814
ENSE00003713950	15623105	15623375
ENSE00003723045	15622219	15622340
ENSE00003749978	15618000	15618144

Expression profiles

Bgee: expression breadth ubiquitous, 118 present calls, max score 99.64.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.2914 / max 5478.5342, expressed in 12 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174318	5.1427	12
174336	0.0498	2
174340	0.0392	2
174332	0.0269	2
174333	0.0217	3
174337	0.0111	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	99.64	gold quality
upper leg skin	UBERON:0004262	84.54	gold quality
mammalian vulva	UBERON:0000997	82.22	gold quality
skin of abdomen	UBERON:0001416	75.23	gold quality
upper arm skin	UBERON:0004263	74.61	gold quality
prostate gland	UBERON:0002367	69.93	gold quality
zone of skin	UBERON:0000014	68.89	gold quality
skin of leg	UBERON:0001511	65.77	gold quality
sperm	CL:0000019	65.55	silver quality
right uterine tube	UBERON:0001302	65.09	gold quality
nipple	UBERON:0002030	64.52	gold quality
male germ cell	CL:0000015	64.42	silver quality
urinary bladder	UBERON:0001255	60.36	gold quality
gluteal muscle	UBERON:0002000	57.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	56.94	silver quality
parotid gland	UBERON:0001831	56.93	gold quality
gall bladder	UBERON:0002110	54.83	gold quality
colonic epithelium	UBERON:0000397	54.21	gold quality
myocardium	UBERON:0002349	53.77	gold quality
lower esophagus mucosa	UBERON:0035834	53.22	gold quality
vagina	UBERON:0000996	53.07	gold quality
triceps brachii	UBERON:0001509	52.84	gold quality
cerebellar vermis	UBERON:0004720	52.51	gold quality
tendon of biceps brachii	UBERON:0008188	51.70	gold quality
saliva-secreting gland	UBERON:0001044	51.62	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	51.01	gold quality
minor salivary gland	UBERON:0001830	50.19	gold quality
thymus	UBERON:0002370	49.48	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting CYP4F8, 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-6756-5P	99.82	67.97	2466
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-4313	97.18	63.15	420
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-500B-3P	96.49	65.40	1087
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722

Literature-anchored findings (GeneRIF, showing 5)

• expression analysis of CYP4F8 shows that high levels are found in epithelial linings and epidermis of psoriatic lesions (PMID:12464258)
• PGH synthase-2, CYP4F8, and PGE synthase-1 likely forms 19-hydroxy-PGE compounds in seminal vesicles and vas deferens (PMID:15789615)
• We conclude that CYP4F8 and CYP4F12 catalyze epoxidation of 22:6n-3 and 22:5n-3, and CYP4F8 omega3-hydroxylation of 22:5n-6. (PMID:16112640)
• The PLA2G7, HPGD, EPHX2, and CYP4F8 genes are highly expressed in prostate cancer. (PMID:21281786)
• New Proluciferin Substrates for Human CYP4 Family Enzymes. (PMID:32869209)

Cross-species orthologs

37 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cyp4f13	ENSMUSG00000024055
mus_musculus	Cyp4f16	ENSMUSG00000048440
mus_musculus	Cyp4f37	ENSMUSG00000062464
mus_musculus	Cyp4f17	ENSMUSG00000091586
rattus_norvegicus	Cyp4f39	ENSRNOG00000029478
rattus_norvegicus	Cyp4f37	ENSRNOG00000042496
rattus_norvegicus	Cyp4f6	ENSRNOG00000043233
rattus_norvegicus	Cyp4f37	ENSRNOG00000048450
rattus_norvegicus		ENSRNOG00000067067
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), CYP4F3 (ENSG00000186529), CYP4A11 (ENSG00000187048)

Protein

Protein identifiers

Cytochrome P450 4F8 — P98187 (reviewed: P98187)

Alternative names: CYPIVF8

All UniProt accessions (4): A0A087WUC9, A0A087WVG9, A0A087WZJ1, P98187

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of endogenous polyunsaturated fatty acids (PUFAs) 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). Catalyzes the hydroxylation of carbon hydrogen bonds, with preference for omega-1 and omega-2 positions. Hydroxylates (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) predominantly at omega-2 position to form (18R)-hydroxyeicosatetraenoic acid (18R-HETE). Exhibits omega-1 hydroxylase activity toward prostaglandin (PG) H1, PGH2 and PGI2. Catalyzes the epoxidation of double bonds of PUFAs, including docosahexaenoic and docosapentaenoic acids. Shows little activity against PGD2, PGE1, PGE2, PGF2alpha, and leukotriene B4.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Expressed in the epithelium of seminal vesicles, in renal cortex, in adult and fetal liver, in epidermis, in corneal epithelium, in sweat glands, hair follicles, epithelial linings of the ampulla of vas deferens and of the stomach and small intestine, as well as in the transitional epithelium of the bladder and ureter (at protein level). In the epidermis, expressed from the basal cell to the granular cell layers. In the corneal epithelium, expressed in all cell layers. Also detected in prostate. Up-regulated in the epidermis of psoriatic lesions.

Pathway. Lipid metabolism; fatty acid metabolism.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (1): NP_009184* (*=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.B9 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Catalyzed reactions (Rhea), 12 shown:

• an organic molecule + reduced [NADPH–hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17149)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH–hemoprotein reductase] + O2 = (18R)-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:48736)
• prostaglandin H2 + reduced [NADPH–hemoprotein reductase] + O2 = 19-hydroxyprostaglandin H2 + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:48776)
• prostaglandin H1 + reduced [NADPH–hemoprotein reductase] + O2 = 19-hydroxyprostaglandin H1 + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:48796)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 19,20-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51080)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 16,17-epoxy-(4Z,7Z,10Z,13Z,19Z)-docosapentaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51084)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 13,14-epoxy-(4Z,7Z,10Z,16Z,19Z)-docosapentaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51088)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 10,11-epoxy-(4Z,7Z,13Z,16Z,19Z)-docosapentaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51092)
• (7Z,10Z,13Z,16Z,19Z)-docosapentaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 19,20-epoxy-(7Z,10Z,13Z,16Z)-docosatetraenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51096)
• (7Z,10Z,13Z,16Z,19Z)-docosapentaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 16,17-epoxy-(7Z,10Z,13Z,19Z)-docosatetraenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51100)
• (7Z,10Z,13Z,16Z,19Z)-docosapentaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 13,14-epoxy-(7Z,10Z,16Z,19Z)-docosatetraenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51104)
• (7Z,10Z,13Z,16Z,19Z)-docosapentaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 10,11-epoxy-(7Z,13Z,16Z,19Z)-docosatetraenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51108)

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P98187-F1	91.45	0.77

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): 468 (axial binding residue)

Mutagenesis-validated functional residues (1):

Position	Phenotype
328	no effect on u-44069 and u-51605 hydroxylation. 20:4n-6 hydroxylation shifted from c-18 to c-19.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 92 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOZGIT_ESR1_TARGETS_UP, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, SANSOM_APC_TARGETS_DN, GOBP_UNSATURATED_FATTY_ACID_METABOLIC_PROCESS

GO Biological Process (7): icosanoid metabolic process (GO:0006690), prostaglandin metabolic process (GO:0006693), arachidonate metabolic process (GO:0019369), menaquinone catabolic process (GO:0042361), phylloquinone catabolic process (GO:0042376), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (8): monooxygenase activity (GO:0004497), 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), alkane 1-monooxygenase activity (GO:0018685), heme binding (GO:0020037), 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)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cytochrome P450 - arranged by substrate type	2
Arachidonate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity	2
carboxylic acid metabolic process	1
prostanoid metabolic process	1
long-chain fatty acid metabolic process	1
icosanoid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
menaquinone metabolic process	1
ketone catabolic process	1
vitamin K catabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
transition metal ion binding	1
monooxygenase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced iron-sulfur protein as one donor, and incorporation of one atom of 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

1534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP4F8	PLAG1	Q6DJT9	729
CYP4F8	PTGS2	P35354	464
CYP4F8	CYP2W1	Q8TAV3	426
CYP4F8	ETFB	P38117	403
CYP4F8	CYB5R4	Q7L1T6	387
CYP4F8	CYB5R1	Q9UHQ9	385
CYP4F8	PPIG	Q13427	378
CYP4F8	CYB5R3	P00387	372
CYP4F8	CYB5B	O43169	369
CYP4F8	SLC27A5	Q9Y2P5	364
CYP4F8	TIMM13	P62206	304
CYP4F8	EPHX2	P34913	304
CYP4F8	C9K0I3	C9K0I3	301
CYP4F8	CYB5R2	Q6BCY4	286
CYP4F8	PLEKHA4	Q9H4M7	279

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CYP4F12	CYP4F2	psi-mi:“MI:0914”(association)	0.530
ankX	CYP4F8	psi-mi:“MI:0915”(physical association)	0.400
	NBAS	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CYP4F8	APOD	psi-mi:“MI:0914”(association)	0.350
DBNL	CYP4F8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): CYP4F8 (Affinity Capture-MS), CYP4F8 (Affinity Capture-MS), CYP4F8 (Affinity Capture-MS), CYP4F8 (Affinity Capture-MS), CYP4F8 (Affinity Capture-RNA), APOD (Affinity Capture-MS), CYP4F8 (Affinity Capture-MS), CTU2 (Affinity Capture-MS), CLU (Affinity Capture-MS), MUCL1 (Affinity Capture-MS), VAMP3 (Cross-Linking-MS (XL-MS)), PCYOX1 (Cross-Linking-MS (XL-MS))

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: A0A084R1M7, A0A0C3HJL3, A0A0E3D8P5, A0A0F7TN11, A0A0F7TN60, A0A0U4ZPJ7, A0A140JWT4, A0A140JWT6, A0A1B4XBJ9, A0A1V6PB34, A0A1V6PBE7, A0A3T0ZHK6, A0A8D5M8I1, A1DA65, A4D9R3, B1GVX2, B6HJU3, B9WZX6, C8VN91, F1SYD1, G5EJN7, G9MLG2, L7WRY5, M1V8J8, O94142, P05183, P0DKI7, P18125, P51869, P51871, P78329, P98187, P9WEQ9, Q0C8A1, Q0C8M4, Q2QYH7, Q3MID2, Q4WAX0, Q5AR29, Q5TCH4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1948 predictions. Top by Δscore:

Variant	Effect	Δscore
19:15619461:T:G	acceptor_gain	1.0000
19:15622338:GGA:G	donor_gain	1.0000
19:15622339:GAG:G	donor_gain	1.0000
19:15622341:G:GG	donor_gain	1.0000
19:15624093:TGGTG:T	donor_loss	1.0000
19:15624095:G:GC	donor_loss	1.0000
19:15624096:T:G	donor_loss	1.0000
19:15628297:CTTA:C	acceptor_loss	1.0000
19:15628299:TA:T	acceptor_loss	1.0000
19:15628300:A:AG	acceptor_gain	1.0000
19:15628300:AG:A	acceptor_gain	1.0000
19:15628301:G:GG	acceptor_gain	1.0000
19:15628301:GG:G	acceptor_gain	1.0000
19:15628301:GGGAC:G	acceptor_gain	1.0000
19:15628399:G:GT	donor_gain	1.0000
19:15628453:G:T	donor_gain	1.0000
19:15629191:AG:A	acceptor_gain	1.0000
19:15629192:GG:G	acceptor_gain	1.0000
19:15615810:GCCTG:G	donor_gain	0.9900
19:15615812:CTGGT:C	donor_loss	0.9900
19:15615813:TGG:T	donor_loss	0.9900
19:15615815:G:A	donor_loss	0.9900
19:15615815:G:GG	donor_gain	0.9900
19:15615816:TGAGT:T	donor_loss	0.9900
19:15615817:G:GT	donor_loss	0.9900
19:15619361:AT:A	acceptor_gain	0.9900
19:15619362:T:G	acceptor_gain	0.9900
19:15619362:T:TA	acceptor_gain	0.9900
19:15619363:G:A	acceptor_gain	0.9900
19:15619460:AT:A	acceptor_gain	0.9900

AlphaMissense

3430 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:15628348:A:C	S388R	0.989
19:15628350:C:A	S388R	0.989
19:15628350:C:G	S388R	0.989
19:15628827:T:C	F461L	0.985
19:15628829:C:A	F461L	0.985
19:15628829:C:G	F461L	0.985
19:15628779:T:C	F445L	0.981
19:15628781:C:A	F445L	0.981
19:15628781:C:G	F445L	0.981
19:15619680:G:C	R148P	0.979
19:15622225:T:A	W178R	0.976
19:15622225:T:C	W178R	0.976
19:15619700:T:C	F155L	0.972
19:15619702:C:A	F155L	0.972
19:15619702:C:G	F155L	0.972
19:15628581:T:A	W434R	0.971
19:15628581:T:C	W434R	0.971
19:15623994:T:A	W339R	0.969
19:15623994:T:C	W339R	0.969
19:15628336:T:C	C384R	0.966
19:15628346:A:T	E387V	0.966
19:15629260:T:C	F489L	0.965
19:15629262:C:A	F489L	0.965
19:15629262:C:G	F489L	0.965
19:15624043:G:C	R355P	0.963
19:15619537:T:A	W131R	0.962
19:15619537:T:C	W131R	0.962
19:15623744:G:C	A322P	0.962
19:15628818:T:C	F458L	0.961
19:15628820:T:A	F458L	0.961

dbSNP variants (sampled 300 via entrez): RS1000239698 (19:15627568 T>G), RS1000589028 (19:15629105 G>T), RS1000843460 (19:15619056 G>A,T), RS1000845585 (19:15617851 A>C), RS1000915643 (19:15618862 C>A,G,T), RS1001073992 (19:15624616 A>G), RS1001087872 (19:15630339 C>T), RS1001472252 (19:15618561 G>A,T), RS1001575384 (19:15619961 G>A), RS1002148198 (19:15624036 C>G,T), RS1002246030 (19:15621254 AGGGTTGACC>A), RS1002343556 (19:15618244 C>G,T), RS1002386605 (19:15629734 C>T), RS1002436966 (19:15618568 G>A,C), RS1002615686 (19:15614513 A>G)

Disease associations

OMIM: gene MIM:611545 | 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
GCST001371_14	Inflammatory biomarkers	3.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523270 (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

ChEMBL bioactivities

16 potent at pChembl≥5 of 19 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 476 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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
alpha-terpineol	decreases reaction, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
linalool	decreases reaction, increases expression	1
gamma-terpinene	decreases reaction, increases expression	1
terpinenol-4	decreases reaction, increases expression	1
lavender oil	decreases reaction, increases expression	1
linalyl acetate	decreases reaction, increases expression	1
walrycin A	increases expression	1
Limonene	increases expression, decreases reaction	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Flutamide	decreases reaction, increases expression	1
Nickel	decreases expression	1
Silicon Dioxide	decreases expression	1
Dihydrotestosterone	increases expression	1
Testosterone	decreases reaction, increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tretinoin	increases expression	1
Isotretinoin	decreases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1
Tea Tree Oil	decreases reaction, increases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

187 unique, capped per target: 185 admet, 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4406426	ADMET	Inhibition of CYP4F8 (unknown origin) in human HepG2 cell membranes transduced with lentiviral vector at 30 uM using Luc-BE as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by P450-g	Design and Characterization of the First Selective and Potent Mechanism-Based Inhibitor of Cytochrome P450 4Z1. — J Med Chem
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.