CYP4F12

Summary

CYP4F12 (cytochrome P450 family 4 subfamily F member 12, HGNC:18857) is a protein-coding gene on chromosome 19p13.12, encoding Cytochrome P450 4F12 (Q9HCS2). A cytochrome P450 monooxygenase involved in the metabolism of endogenous polyunsaturated fatty acids (PUFAs).

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 protein likely localizes to the endoplasmic reticulum. When expressed in yeast the enzyme is capable of oxdizing arachidonic acid. It can also catalyze the epoxidation of 22:6n-3 and 22:5n-3 polyunsaturated long-chain fatty acids. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 66002 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 110 total
• Druggable target: yes
• MANE Select transcript: NM_023944

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18857
Approved symbol	CYP4F12
Name	cytochrome P450 family 4 subfamily F member 12
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000186204
Ensembl biotype	protein_coding
OMIM	611485
Entrez	66002

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 13 protein_coding, 10 retained_intron, 4 nonsense_mediated_decay

ENST00000324632, ENST00000430608, ENST00000451750, ENST00000517734, ENST00000518629, ENST00000546608, ENST00000546792, ENST00000547332, ENST00000547471, ENST00000548237, ENST00000548435, ENST00000548501, ENST00000549622, ENST00000550264, ENST00000550308, ENST00000550627, ENST00000551607, ENST00000893772, ENST00000893773, ENST00000893774, ENST00000893775, ENST00000893776, ENST00000893777, ENST00000893778, ENST00000893779, ENST00000893780, ENST00000966234

RefSeq mRNA: 1 — MANE Select: NM_023944 NM_023944

CCDS: CCDS42517

Canonical transcript exons

ENST00000550308 — 13 exons

Exon	Start	End
ENSE00001716993	15696161	15696225
ENSE00001803579	15696430	15696512
ENSE00002380650	15696908	15697174
ENSE00002382177	15673087	15673135
ENSE00003472733	15673529	15673727
ENSE00003487757	15684816	15684882
ENSE00003494887	15680392	15680519
ENSE00003502167	15680244	15680297
ENSE00003525730	15695936	15696069
ENSE00003531636	15683493	15683763
ENSE00003580210	15685068	15685197
ENSE00003601049	15678261	15678405
ENSE00003658885	15682389	15682510

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 97.20.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4191 / max 138.9770, expressed in 247 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174347	1.4191	247

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.20	gold quality
ileal mucosa	UBERON:0000331	95.91	gold quality
tongue squamous epithelium	UBERON:0006919	95.78	gold quality
right lobe of liver	UBERON:0001114	95.50	gold quality
duodenum	UBERON:0002114	95.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.28	gold quality
lower esophagus mucosa	UBERON:0035834	95.28	gold quality
skin of abdomen	UBERON:0001416	94.99	gold quality
skin of leg	UBERON:0001511	94.51	gold quality
transverse colon	UBERON:0001157	94.34	gold quality
small intestine	UBERON:0002108	94.26	gold quality
jejunal mucosa	UBERON:0000399	94.02	gold quality
rectum	UBERON:0001052	93.81	gold quality
gingival epithelium	UBERON:0001949	93.74	gold quality
olfactory bulb	UBERON:0002264	93.51	gold quality
esophagus mucosa	UBERON:0002469	93.44	gold quality
type B pancreatic cell	CL:0000169	92.99	gold quality
nasal cavity epithelium	UBERON:0005384	92.99	gold quality
zone of skin	UBERON:0000014	92.87	gold quality
liver	UBERON:0002107	92.66	gold quality
gingiva	UBERON:0001828	92.33	gold quality
pancreatic ductal cell	CL:0002079	91.50	silver quality
cervix squamous epithelium	UBERON:0006922	91.50	silver quality
diaphragm	UBERON:0001103	91.10	gold quality
mucosa of stomach	UBERON:0001199	90.99	gold quality
upper arm skin	UBERON:0004263	90.86	gold quality
intestine	UBERON:0000160	90.46	gold quality
vagina	UBERON:0000996	89.63	gold quality
colon	UBERON:0001155	89.62	gold quality
large intestine	UBERON:0000059	89.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NCOA1, NR1I2, PPARA, RXRA

Literature-anchored findings (GeneRIF, showing 7)

• 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)
• 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)
• Our results showed that HCV infection induced expression of CYP4F12 protein, which bound to the HCV replication complex to facilitate viral replication. (PMID:26845356)
• These results suggest that human and marmoset P450 3A4/90 and 4F12 in livers or small intestines played important roles in terfenadine t-butyl hydroxylation. Marmosets could be a model for humans during first pass extraction of terfenadine and related substrates. (PMID:28436281)
• Genetic variants of CYP4F12 gene are associated with glioma susceptibility. (PMID:34319593)
• CYP4F12 is a potential biomarker and inhibits cell migration of head and neck squamous cell carcinoma via EMT pathway. (PMID:37414830)
• Integrative Analysis of Histone Acetylation Regulated CYP4F12 in Esophageal Cancer Development. (PMID:38811154)

Cross-species orthologs

36 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp4t8	ENSDARG00000004964
danio_rerio	cyp4f3	ENSDARG00000053530
mus_musculus	Cyp4a31	ENSMUSG00000028712
mus_musculus	Cyp4a32	ENSMUSG00000063929
mus_musculus	Cyp4a10	ENSMUSG00000066072
mus_musculus	Cyp4a30b	ENSMUSG00000084346
rattus_norvegicus	Cyp4a1	ENSRNOG00000009597
rattus_norvegicus	Cyp4a3	ENSRNOG00000066878
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), CYP4X1 (ENSG00000186377), CYP4F8 (ENSG00000186526), CYP4F3 (ENSG00000186529), CYP4A11 (ENSG00000187048)

Protein

Protein identifiers

Cytochrome P450 4F12 — Q9HCS2 (reviewed: Q9HCS2)

Alternative names: CYPIVF12

All UniProt accessions (4): Q9HCS2, F8VR75, F8VU50, F8VZP1

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of endogenous polyunsaturated fatty acids (PUFAs). 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-2 position. Metabolizes (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) toward 18-hydroxy arachidonate. Catalyzes the epoxidation of double bonds of PUFAs such as docosapentaenoic and docosahexaenoic acids. Has low omega-hydroxylase activity toward leukotriene B4 and arachidonate. Involved in the metabolism of xenobiotics. Catalyzes the hydroxylation of the antihistamine drug ebastine.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Expressed in small intestine, liver, colon and heart.

Pathway. Lipid metabolism; arachidonate metabolism.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HCS2-1	1	yes
Q9HCS2-2	2

RefSeq proteins (1): NP_076433* (*=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), 10 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 = 18-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39811)
• (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 (12 total): sequence variant 6, transmembrane region 2, splice variant 2, chain 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCS2-F1	90.97	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): 468 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-211935	Fatty acids
R-HSA-211979	Eicosanoids

MSigDB gene sets: 155 (showing top): GOBP_FATTY_ACID_CATABOLIC_PROCESS, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GNF2_GSTM1, GOBP_RENAL_SYSTEM_PROCESS_INVOLVED_IN_REGULATION_OF_BLOOD_VOLUME, GNF2_HPN, MORF_ATRX, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, MODULE_16, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, MORF_PPP5C

GO Biological Process (14): very long-chain fatty acid metabolic process (GO:0000038), long-chain fatty acid metabolic process (GO:0001676), renal water homeostasis (GO:0003091), pressure natriuresis (GO:0003095), fatty acid metabolic process (GO:0006631), xenobiotic metabolic process (GO:0006805), arachidonate metabolic process (GO:0019369), epoxygenase P450 pathway (GO:0019373), leukotriene B4 catabolic process (GO:0036101), vitamin E metabolic process (GO:0042360), menaquinone catabolic process (GO:0042361), phylloquinone catabolic process (GO:0042376), sodium ion homeostasis (GO:0055078), lipid metabolic process (GO:0006629)

GO Molecular Function (11): monooxygenase activity (GO:0004497), iron ion binding (GO:0005506), arachidonate epoxygenase activity (GO:0008392), alkane 1-monooxygenase activity (GO:0018685), heme binding (GO:0020037), leukotriene-B4 20-monooxygenase activity (GO:0050051), protein binding (GO:0005515), 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 (6): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), apical plasma membrane (GO:0016324), intracellular membrane-bounded organelle (GO:0043231), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cytochrome P450 - arranged by substrate type	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fatty acid metabolic process	2
renal system process	2
metabolic process	2
oxidoreductase activity	2
intracellular anatomical structure	2
cellular anatomical structure	2
multicellular organismal-level water homeostasis	1
regulation of body fluid levels	1
lipid metabolic process	1
monocarboxylic acid 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
arachidonate 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
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
primary metabolic process	1
transition metal ion binding	1
arachidonate monooxygenase activity	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
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
leukotriene B4 catabolic process	1
binding	1
catalytic activity	1
monooxygenase 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

Protein interactions and networks

STRING

1512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP4F12	F5H3C5	F5H3C5	505
CYP4F12	SOD2	P04179	505
CYP4F12	PPIG	Q13427	478
CYP4F12	NCOA2	Q15596	453
CYP4F12	GSTO1	P78417	401
CYP4F12	PTGES3	Q15185	353
CYP4F12	CNR1	P21554	352
CYP4F12	CNR2	P34972	352
CYP4F12	CYB5B	O43169	342
CYP4F12	UGT1A6	P19224	331
CYP4F12	GARIN1A	Q6NXP2	325
CYP4F12	CYB5A	P00167	324
CYP4F12	ARNT	P27540	310
CYP4F12	VKORC1	Q9BQB6	310
CYP4F12	NR1I2	O75469	301

IntAct

20 interactions, top by confidence:

A	B	Type	Score
POLE2	CYP4F12	psi-mi:“MI:0914”(association)	0.560
CYP4F12	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	CYP4F12	psi-mi:“MI:0915”(physical association)	0.560
POLE2	CYP4F12	psi-mi:“MI:0915”(physical association)	0.560
CYP4F12	CYP4F2	psi-mi:“MI:0914”(association)	0.530
CYP4F12	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CREB3	CYP4F12	psi-mi:“MI:0915”(physical association)	0.370
CYP4F12	CREB3	psi-mi:“MI:0915”(physical association)	0.370
CYP4F12	HSPA6	psi-mi:“MI:0915”(physical association)	0.370
CYP4F12	SOD2	psi-mi:“MI:0915”(physical association)	0.370
CFTR	CYP4F12	psi-mi:“MI:0915”(physical association)	0.370
ZBTB18	ZBTB42	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350
CYP4F12	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): CYP4F12 (Affinity Capture-Western), CYP4F12 (Two-hybrid), CYP4F2 (Affinity Capture-MS), CYP4F8 (Affinity Capture-MS), CYP4F12 (Affinity Capture-MS), CYP4F12 (Affinity Capture-MS), RPS6KA4 (Negative Genetic), PTK6 (Negative Genetic), GPX1 (Negative Genetic), CYP4F12 (Negative Genetic), CYP4F12 (Negative Genetic), MAP3K10 (Negative Genetic), KCNQ4 (Negative Genetic), STMN1 (Negative Genetic), FABP4 (Negative Genetic)

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, A0A0E3D8P0, A0A140JWM8, A0A1B4XBH8, A0A3Q7HBJ5, A0A517FNB9, A0A517FNC5, A0A5B8ND22, A0A9Y1LLN2, A2QTE8, A2RRT9, A2Z212, A9QNE7, B5BSX1, B8AV52, B8BJ22, D4AY62, I1IUJ6, I7ZK32, K4CI52, L0N063, O13820, O23051, O46515, O81077, P05108, P0DXH4, P12394, P14137, P29981, P30612, P36423, P37121, P51870, P51871, P70085, P78329, P79690, P93147

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2090 predictions. Top by Δscore:

Variant	Effect	Δscore
19:15680212:A:AG	acceptor_gain	1.0000
19:15680212:ACAT:A	acceptor_gain	1.0000
19:15680212:ACATG:A	acceptor_gain	1.0000
19:15680214:A:AG	acceptor_gain	1.0000
19:15680214:AT:A	acceptor_gain	1.0000
19:15680214:ATG:A	acceptor_gain	1.0000
19:15680215:T:G	acceptor_gain	1.0000
19:15680215:T:TA	acceptor_gain	1.0000
19:15680216:G:A	acceptor_gain	1.0000
19:15680515:TGCTT:T	donor_gain	1.0000
19:15680516:GCTTG:G	donor_gain	1.0000
19:15682508:GGA:G	donor_gain	1.0000
19:15682509:GA:G	donor_gain	1.0000
19:15682509:GAG:G	donor_gain	1.0000
19:15682511:G:GG	donor_gain	1.0000
19:15683483:T:A	acceptor_gain	1.0000
19:15683489:GCAGG:G	acceptor_loss	1.0000
19:15683490:CA:C	acceptor_loss	1.0000
19:15683490:CAGG:C	acceptor_gain	1.0000
19:15683491:A:AG	acceptor_gain	1.0000
19:15683491:AG:A	acceptor_gain	1.0000
19:15683491:AGGA:A	acceptor_gain	1.0000
19:15683491:AGGAG:A	acceptor_gain	1.0000
19:15683492:G:GT	acceptor_gain	1.0000
19:15683492:GG:G	acceptor_gain	1.0000
19:15683492:GGA:G	acceptor_gain	1.0000
19:15683492:GGAG:G	acceptor_gain	1.0000
19:15683492:GGAGG:G	acceptor_gain	1.0000
19:15683759:GCAAG:G	donor_gain	1.0000
19:15683763:GGT:G	donor_gain	1.0000

AlphaMissense

3467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:15695982:A:C	S388R	0.992
19:15695984:C:A	S388R	0.992
19:15695984:C:G	S388R	0.992
19:15696448:T:C	F445L	0.989
19:15696450:T:A	F445L	0.989
19:15696450:T:G	F445L	0.989
19:15696496:T:C	F461L	0.987
19:15696498:C:A	F461L	0.987
19:15696498:C:G	F461L	0.987
19:15695980:A:T	E387V	0.984
19:15695989:G:C	R390T	0.982
19:15695970:T:C	C384R	0.980
19:15695990:G:C	R390S	0.980
19:15695990:G:T	R390S	0.980
19:15685142:T:C	C354R	0.978
19:15685144:C:G	C354W	0.977
19:15685146:G:C	R355P	0.977
19:15682395:T:A	W178R	0.974
19:15682395:T:C	W178R	0.974
19:15695979:G:A	E387K	0.974
19:15696211:T:A	W434R	0.973
19:15696211:T:C	W434R	0.973
19:15696487:T:C	F458L	0.973
19:15696489:T:A	F458L	0.973
19:15696489:T:G	F458L	0.973
19:15695972:C:G	C384W	0.972
19:15695989:G:T	R390M	0.972
19:15685097:T:A	W339R	0.970
19:15685097:T:C	W339R	0.970
19:15680437:G:C	R148P	0.968

dbSNP variants (sampled 300 via entrez): RS1000017416 (19:15689651 T>C), RS1000079460 (19:15674694 T>C,G), RS1000280461 (19:15679859 A>G), RS1000592893 (19:15671369 A>C), RS1000617577 (19:15681080 T>C), RS1000877244 (19:15691948 T>C), RS1000922385 (19:15695109 C>A), RS1001381769 (19:15691538 A>C,G), RS1001749547 (19:15691180 C>A,T), RS1001960700 (19:15678820 G>A,T), RS1002303896 (19:15671114 G>C), RS1002379032 (19:15695435 A>C), RS1002473504 (19:15671326 G>A), RS1002556693 (19:15691358 C>G), RS1002567536 (19:15683046 T>C)

Disease associations

OMIM: gene MIM:611485 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010245_14	LDL cholesterol levels	8.000000e-10
GCST90020047_1	Glioma	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3509589 (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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
HET0016	Inhibition	5.47	pIC50

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.81	IC50	155.3	nM	CHEMBL267865
5.80	IC50	1598	nM	CHEMBL5272822

PubChem BioAssay actives

2 with measured affinity, of 21 total; 2 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
N’-(4-butyl-2-methylphenyl)-N-hydroxymethanimidamide	1935290: Inhibition of human recombinant CYP4F12 using Luciferin ME EGE as substrate incubated for 30 mins in presence of NADPH by luminescence based assay	ic50	0.1553	uM
ethyl 4-[4-[(hydroxyamino)methylideneamino]phenyl]butanoate	1935290: Inhibition of human recombinant CYP4F12 using Luciferin ME EGE as substrate incubated for 30 mins in presence of NADPH by luminescence based assay	ic50	1.5983	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aminomethylphosphonic acid (AMPA)	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
sodium arsenate	increases abundance, decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
fipronil	affects cotreatment, decreases expression	1
JP8 aviation fuel	affects expression	1
obeticholic acid	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	increases expression	1
Glyphosate	decreases expression	1
Air Pollutants	decreases expression	1
Ethanol	increases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Biological Factors	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
DEET	affects cotreatment, decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3531396	ADMET	Activity of human recombinant CYP4F12 assessed as enzyme-mediated 2-hydroxyethyl (1R,3aR,4aR,6R,8aR,9S,9aS)-9-((E)-2-(5-(3-fluorophenyl)pyridin-2-yl)vinyl)-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-ylcarbamate formation at 25 uM after	Identification of human liver cytochrome P450 enzymes involved in the metabolism of SCH 530348 (Vorapaxar), a potent oral thrombin protease-activated receptor 1 antagonist. — Drug Metab Dispos

Clinical trials (associated diseases)

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