CYP2S1

Summary

CYP2S1 (cytochrome P450 family 2 subfamily S member 1, HGNC:15654) is a protein-coding gene on chromosome 19q13.2, encoding Cytochrome P450 2S1 (Q96SQ9). A cytochrome P450 monooxygenase involved in the metabolism of retinoids and eicosanoids.

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 localizes to the endoplasmic reticulum. In rodents, the homologous protein has been shown to metabolize certain carcinogens; however, the specific function of the human protein has not been determined.

Source: NCBI Gene 29785 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 97 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_030622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15654
Approved symbol	CYP2S1
Name	cytochrome P450 family 2 subfamily S member 1
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167600
Ensembl biotype	protein_coding
OMIM	611529
Entrez	29785

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 2 nonsense_mediated_decay

ENST00000310054, ENST00000593545, ENST00000593890, ENST00000595590, ENST00000597754, ENST00000600561, ENST00000880809, ENST00000880810, ENST00000922088, ENST00000922089, ENST00000922090, ENST00000922091, ENST00000922092, ENST00000922093, ENST00000922094, ENST00000922095

RefSeq mRNA: 1 — MANE Select: NM_030622 NM_030622

CCDS: CCDS12573

Canonical transcript exons

ENST00000310054 — 9 exons

Exon	Start	End
ENSE00001114766	41197779	41197928
ENSE00001114767	41198709	41198888
ENSE00001114771	41198462	41198622
ENSE00001410924	41206280	41207539
ENSE00003109255	41193219	41193441
ENSE00003467747	41203450	41203637
ENSE00003496647	41205958	41206099
ENSE00003578703	41201231	41201372
ENSE00003628355	41194544	41194709

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 94.84.

FANTOM5 (CAGE): breadth broad, TPM avg 7.2423 / max 229.2970, expressed in 874 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175927	4.6422	721
175926	2.5402	634
175925	0.0600	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	94.84	gold quality
jejunal mucosa	UBERON:0000399	93.46	gold quality
duodenum	UBERON:0002114	91.65	gold quality
nasal cavity epithelium	UBERON:0005384	89.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.84	gold quality
mucosa of transverse colon	UBERON:0004991	85.87	gold quality
rectum	UBERON:0001052	85.81	gold quality
body of stomach	UBERON:0001161	84.47	gold quality
tibialis anterior	UBERON:0001385	82.47	silver quality
stomach	UBERON:0000945	81.82	gold quality
small intestine	UBERON:0002108	81.79	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.70	gold quality
esophagus mucosa	UBERON:0002469	81.04	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.01	silver quality
lower esophagus mucosa	UBERON:0035834	79.97	gold quality
colonic mucosa	UBERON:0000317	79.90	gold quality
monocyte	CL:0000576	79.55	gold quality
leukocyte	CL:0000738	79.32	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.28	gold quality
transverse colon	UBERON:0001157	77.63	gold quality
mucosa of stomach	UBERON:0001199	77.39	gold quality
vermiform appendix	UBERON:0001154	77.38	gold quality
bronchial epithelial cell	CL:0002328	76.89	gold quality
jejunum	UBERON:0002115	76.81	gold quality
granulocyte	CL:0000094	76.67	gold quality
oral cavity	UBERON:0000167	76.39	gold quality
bronchus	UBERON:0002185	76.12	gold quality
pharyngeal mucosa	UBERON:0000355	75.87	gold quality
gall bladder	UBERON:0002110	75.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	11.88
E-ANND-3	yes	10.60
E-MTAB-7008	no	306.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting CYP2S1, 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-574-5P	100.00	66.01	989
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-5094	98.63	67.11	1062
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-3138	98.41	67.53	744
HSA-MIR-147A	98.33	66.40	795
HSA-MIR-92A-1-5P	98.28	64.51	631

Literature-anchored findings (GeneRIF, showing 23)

• identify a novel regulatory cassette that mediates changes in Cyp2s1 expression (PMID:17277313)
• The presence of a CYP2A-related protein and testosterone metabolism in stellate cell cultures suggest that stellate cells express specific functional isoforms of CYP of which a major form is CYP2S1 (PMID:17280660)
• identified the following three novel single nucleotide polymorphisms (SNPs): 4612G>A (Glu147Glu) in exon 3, 5478C>T (Leu230Leu) and 5479T>G (Leu230Arg, CYP2S1*5A) in exon 5 in Japanese individuals (PMID:17495422)
• 12 genetic variations, which included the two novel nonsynonymous mutations CYP2S1 S61N (0.3%) and CYP2S1 L230R (0.8%), were identified in 50 Korean subjects (PMID:17529885)
• Review compares the expression of CYP2S1 mRNA and protein in humans, mice and rats, and critically examines evidence pertaining to CYP2S1 regulation and its catalytic activity. (PMID:19368491)
• CYP2S1 contributes to the metabolism of environmental carcinogens via a nicotinamide adenine dinucleotide phosphate (NADPH)- independent activity. (PMID:19713358)
• P450 2S1 can be reduced by NADPH-P450 reductase and suggest normal mixed-function oxidase roles of P450 2S1 to be revealed. (PMID:21430234)
• Data suggest that CYP2S1 is induced in a keratinocyte cell line by exposure to all-trans retinoic acid and ultraviolet B radiation. (PMID:22039172)
• No association has been found between the CYP2J2 (rs890293, -76G > T) or CYP2S1 (rs34971233, 13106C > T, P466L and rs338583, 13255A > G) gene polymorphisms and respiratory diseases. (PMID:22232929)
• The reduction in CYP2S1 expression doubled intracellular PGE(2) levels. (PMID:22863683)
• found that CYP inhibition and siRNA-mediated downregulation of CYP2S1 increased macrophage phagocytosis (PMID:23224081)
• Biotransformation of (+)-fenchone by Salmonella typhimurium OY1002/2A6 expressing human CYP2A6 and NADPH-P450 reductase. (PMID:23648403)
• The P450 2S1 may be involved in the reductive detoxication of several of the activated products of carcinogenic aromatic amines and heterocyclic aromatic amines. (PMID:23682735)
• CYP2S1 regulates colorectal cancer growth through associated with prostaglandin E2-mediated activation of beta-catenin signaling. (PMID:25557876)
• These results suggest that oxaliplatin exerts its inhibitory effects in human CRC cells via upregulation of CYP2S1 expression in a p53-dependent manner. (PMID:27609465)
• There were 21 genetic variants identified in CYP2S1 in three Chinese populations: Han, Tibetan and Uighur. (PMID:30019995)
• PPARalpha plays an important role in the migration activity, and the expression of CYP2S1 and CYP1B1 in chrysin-treated HCT116 cells. (PMID:32385743)
• CYP2S1 is a synthetic lethal target in BRAF(V600E)-driven thyroid cancers. (PMID:32913191)
• CYP2S1 might regulate proliferation and immune response of keratinocyte in psoriasis. (PMID:32924783)
• Hypoxia as a modulator of cytochromes P450: Overexpression of the cytochromes CYP2S1 and CYP24A1 in human liver cancer cells in hypoxia. (PMID:33377261)
• Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration. (PMID:34275895)
• CYP2S1 rs338599 polymorphism confers reduced risk to anti-tuberculosis drug-induced liver injury and may be a novel marker for its risk prediction. (PMID:35535391)
• CYP2S1 and CYP2W1 expression is associated with patient survival in breast cancer. (PMID:35902379)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cyp2s1	ENSMUSG00000040703
rattus_norvegicus	Cyp2s1	ENSRNOG00000020743

Paralogs (15): CYP2W1 (ENSG00000073067), CYP2D6 (ENSG00000100197), CYP2C18 (ENSG00000108242), CYP2E1 (ENSG00000130649), CYP2J2 (ENSG00000134716), CYP2C9 (ENSG00000138109), CYP2C8 (ENSG00000138115), CYP2U1 (ENSG00000155016), CYP2C19 (ENSG00000165841), CYP2R1 (ENSG00000186104), CYP2B6 (ENSG00000197408), CYP2F1 (ENSG00000197446), CYP2A13 (ENSG00000197838), CYP2A7 (ENSG00000198077), CYP2A6 (ENSG00000255974)

Protein

Protein identifiers

Cytochrome P450 2S1 — Q96SQ9 (reviewed: Q96SQ9)

Alternative names: CYPIIS1, Hydroperoxy icosatetraenoate dehydratase, Thromboxane-A synthase

All UniProt accessions (6): Q96SQ9, M0QY51, M0QYI2, M0R057, M0R152, M0R2G8

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of retinoids and eicosanoids. In epidermis, may contribute to the oxidative metabolism of all-trans-retinoic acid. For this activity, 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 (NADPH–hemoprotein reductase). Additionally, displays peroxidase and isomerase activities toward various oxygenated eicosanoids such as prostaglandin H2 (PGH2) and hydroperoxyeicosatetraenoates (HPETEs). Independently of cytochrome P450 reductase, NADPH, and O2, catalyzes the breakdown of PGH2 to hydroxyheptadecatrienoic acid (HHT) and malondialdehyde (MDA), which is known to act as a mediator of DNA damage.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Expressed at higher levels in extrahepatic tissues including trachea, lung, stomach, small intestine, colon, kidney, breast, placenta and spleen. Expressed in peripheral blood leukocytes. Constitutively expressed in skin (at protein level).

Induction. Up-regulated in skin upon exposure to ultraviolet radiation or treatment with all-trans retinoic acid (substrate-inducible).

Pathway. Lipid metabolism; fatty acid metabolism.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96SQ9-1	1	yes
Q96SQ9-2	2

RefSeq proteins (1): NP_085125* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR008067	Cyt_P450_E_grp-I_CYP2A-like	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050182	Cytochrome_P450_fam2	Family

Pfam: PF00067

Catalyzed reactions (Rhea), 8 shown:

• prostaglandin H2 = thromboxane A2 (RHEA:17137)
• (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = 12-oxo-(5Z,8Z,10E,14Z)-eicosatetraenoate + H2O (RHEA:37947)
• (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = 5-oxo-(6E,8Z,11Z,14Z)-eicosatetraenoate + H2O (RHEA:48632)
• (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H2O (RHEA:48636)
• prostaglandin H2 = (12S)-hydroxy-(5Z,8E,10E)-heptadecatrienoate + malonaldehyde (RHEA:48644)
• (13S)-hydroperoxy-(9Z,11E)-octadecadienoate = 13-oxo-(9Z,11E)-octadecadienoate + H2O (RHEA:48716)
• all-trans-retinoate + reduced [NADPH–hemoprotein reductase] + O2 = all-trans-4-hydroxyretinoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51984)
• all-trans-retinoate + reduced [NADPH–hemoprotein reductase] + O2 = all-trans-5,6-epoxyretinoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:55860)

UniProt features (4 total): chain 1, binding site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96SQ9-F1	92.84	0.86

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): 440 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-211958	Miscellaneous substrates
R-HSA-211981	Xenobiotics
R-HSA-211999	CYP2E1 reactions

MSigDB gene sets: 184 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_RETINOIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, SANSOM_APC_TARGETS_DN, GOMF_HYDRO_LYASE_ACTIVITY, GOBP_UNSATURATED_FATTY_ACID_METABOLIC_PROCESS, GOBP_ARACHIDONATE_METABOLIC_PROCESS, GOBP_PROSTANOID_METABOLIC_PROCESS, GOBP_EPOXYGENASE_P450_PATHWAY

GO Biological Process (8): icosanoid metabolic process (GO:0006690), prostaglandin metabolic process (GO:0006693), xenobiotic metabolic process (GO:0006805), epoxygenase P450 pathway (GO:0019373), retinoic acid metabolic process (GO:0042573), cytochrome metabolic process (GO:1903604), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (16): monooxygenase activity (GO:0004497), thromboxane-A synthase activity (GO:0004796), iron ion binding (GO:0005506), arachidonate epoxygenase activity (GO:0008392), retinoic acid 4-hydroxylase activity (GO:0008401), 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), hydro-lyase activity (GO:0016836), heme binding (GO:0020037), 12-hydroxyheptadecatrienoic acid synthase activity (GO:0036134), hydroperoxy icosatetraenoate dehydratase activity (GO:0106256), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), lyase activity (GO:0016829), isomerase activity (GO:0016853), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cytochrome P450 - arranged by substrate type	2
Xenobiotics	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	3
monocarboxylic acid metabolic process	2
oxidoreductase activity	2
monooxygenase activity	2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	2
cellular anatomical structure	2
carboxylic acid metabolic process	1
prostanoid metabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
arachidonate metabolic process	1
retinoid metabolic process	1
hormone metabolic process	1
protein metabolic process	1
primary metabolic process	1
lipid metabolic process	1
intramolecular oxidoreductase activity	1
transition metal ion binding	1
arachidonate monooxygenase activity	1
carbon-oxygen lyase activity	1
tetrapyrrole binding	1
oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor	1
hydro-lyase activity	1
binding	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

1372 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP2S1	ERP29	P30040	888
CYP2S1	PPIG	Q13427	576
CYP2S1	PTGIS	Q16647	522
CYP2S1	OR6C1	Q96RD1	493
CYP2S1	ALDH3A1	P30838	435
CYP2S1	OR6C3	Q9NZP0	429
CYP2S1	FMO4	P31512	375
CYP2S1	A0A0B4J2F2	A0A0B4J2F2	366
CYP2S1	SIK1	P57059	363
CYP2S1	PRSS22	Q9GZN4	353
CYP2S1	KCNU1	A8MYU2	353
CYP2S1	ADCY5	O95622	353
CYP2S1	EDN3	P14138	352
CYP2S1	FMO1	Q01740	349
CYP2S1	FMO2	Q99518	320

IntAct

71 interactions, top by confidence:

A	B	Type	Score
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
ADAMTSL4	CYP2S1	psi-mi:“MI:0915”(physical association)	0.560
CYP2S1	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	CYP2S1	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	CYP2S1	psi-mi:“MI:0915”(physical association)	0.550
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
CXCR4	FANCA	psi-mi:“MI:0914”(association)	0.530
	TMEM223	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
IGHM	ESYT2	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
GYPA	HYKK	psi-mi:“MI:0914”(association)	0.350
TSPAN10	KLRG2	psi-mi:“MI:0914”(association)	0.350
ORAI1	POTEF	psi-mi:“MI:0914”(association)	0.350
PCDHGC4		psi-mi:“MI:0914”(association)	0.350
VIPR2	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
GCGR	GPR89A	psi-mi:“MI:0914”(association)	0.350
CYP2S1	ARVCF	psi-mi:“MI:0914”(association)	0.350
TPRA1	BMPR1B	psi-mi:“MI:0914”(association)	0.350
GPR12	TLCD2	psi-mi:“MI:0914”(association)	0.350
NT5E	SCAMP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (120): ADAMTSL4 (Two-hybrid), CYP2S1 (Affinity Capture-MS), ADAMTSL4 (Two-hybrid), CYP2S1 (Affinity Capture-MS), CYP2S1 (Affinity Capture-MS), CYP2S1 (Affinity Capture-MS), CADM4 (Affinity Capture-MS), CYP2S1 (Affinity Capture-MS), PRKCA (Affinity Capture-MS), CYP2S1 (Affinity Capture-MS), CYP2S1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), SRC (Affinity Capture-MS), HOXB9 (Affinity Capture-MS), NCAM1 (Affinity Capture-MS)

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

Diamond homologs: A0A067GFT7, A0A068AA98, A0A084API1, A0A0C3HJL3, A0A0F7U0K0, A0A0P0ZEA9, A0A1B4XBH0, A0A1L7VEQ6, A0A1L9WQK2, A0A1R3RGJ7, A0A1V1FNM9, A0A218NGS0, A0A2P1DPA5, A0A386KZI3, A0A3S9NM20, A0A411KUQ5, A0A455ZIK8, A0A455ZM03, A0A481WPJ6, A0A517FNB9, A0A5B8NBK9, A0A5B8ND26, A0A6S6QPY4, A0A831A9C9, A0A8K1AW54, A1C8C2, A2R6G9, A6YIH8, B5BSX1, B6HFX9, B8NHD9, C0SJS4, C8V0D4, C8V7P3, C9K1X6, D1MX85, F1SY77, G0KYB2, G1XU01, G3Y420

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
G alpha (s) signalling events	7	8.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
G protein-coupled receptor signaling pathway	12	5.4×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1045 predictions. Top by Δscore:

Variant	Effect	Δscore
19:41193406:C:G	donor_gain	1.0000
19:41193438:GCGG:G	donor_gain	1.0000
19:41193440:GG:G	donor_gain	1.0000
19:41193441:GG:G	donor_gain	1.0000
19:41193442:G:C	donor_loss	1.0000
19:41193443:T:A	donor_loss	1.0000
19:41194536:A:AG	acceptor_gain	1.0000
19:41194537:C:G	acceptor_gain	1.0000
19:41194708:TGGTA:T	donor_loss	1.0000
19:41194710:GTAA:G	donor_loss	1.0000
19:41194711:T:TC	donor_loss	1.0000
19:41198587:G:GA	donor_gain	1.0000
19:41198599:G:GT	donor_gain	1.0000
19:41198706:CAGAC:C	acceptor_loss	1.0000
19:41198707:A:AG	acceptor_gain	1.0000
19:41198707:AG:A	acceptor_loss	1.0000
19:41198708:G:GT	acceptor_gain	1.0000
19:41198708:GA:G	acceptor_gain	1.0000
19:41198708:GAC:G	acceptor_gain	1.0000
19:41198708:GACC:G	acceptor_gain	1.0000
19:41198708:GACCT:G	acceptor_gain	1.0000
19:41201230:GGA:G	acceptor_gain	1.0000
19:41201367:TCCA:T	donor_gain	1.0000
19:41201370:AAAGT:A	donor_loss	1.0000
19:41201371:AA:A	donor_gain	1.0000
19:41201371:AAGTA:A	donor_loss	1.0000
19:41201373:G:GG	donor_gain	1.0000
19:41201374:T:G	donor_loss	1.0000
19:41203448:A:AG	acceptor_gain	1.0000
19:41203449:G:GT	acceptor_gain	1.0000

AlphaMissense

3209 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:41206042:T:C	F417L	0.982
19:41206044:C:A	F417L	0.982
19:41206044:C:G	F417L	0.982
19:41206027:T:C	F412L	0.978
19:41206029:C:A	F412L	0.978
19:41206029:C:G	F412L	0.978
19:41194658:T:C	F98L	0.972
19:41194660:C:A	F98L	0.972
19:41194660:C:G	F98L	0.972
19:41206009:T:C	F406L	0.962
19:41206011:C:A	F406L	0.962
19:41206011:C:G	F406L	0.962
19:41194568:T:C	F68L	0.961
19:41194570:C:A	F68L	0.961
19:41194570:C:G	F68L	0.961
19:41203549:A:T	E359V	0.961
19:41206090:T:C	F433L	0.960
19:41206092:C:A	F433L	0.960
19:41206092:C:G	F433L	0.960
19:41206028:T:C	F412S	0.952
19:41203536:G:C	A355P	0.951
19:41194605:T:A	V80D	0.949
19:41206354:T:C	F461L	0.949
19:41206356:C:A	F461L	0.949
19:41206356:C:G	F461L	0.949
19:41193396:C:A	N44K	0.945
19:41193396:C:G	N44K	0.945
19:41203615:T:C	F381S	0.944
19:41197823:T:C	F130L	0.943
19:41197825:T:A	F130L	0.943

dbSNP variants (sampled 300 via entrez): RS1000445594 (19:41194881 G>A,T), RS1000457038 (19:41195060 G>A), RS1000605392 (19:41194360 G>A), RS1000780713 (19:41200090 C>T), RS1000792142 (19:41193813 G>A,C), RS1000807602 (19:41204484 C>T), RS1000849136 (19:41198663 G>A,T), RS1000861424 (19:41204757 C>A), RS1001163130 (19:41206210 G>A), RS1001262414 (19:41205329 T>C,G), RS1001479252 (19:41207049 C>T), RS1001644066 (19:41201970 T>C), RS1001719664 (19:41206781 C>T), RS1001811061 (19:41205796 A>G), RS1001972671 (19:41195056 C>T)

Disease associations

OMIM: gene MIM:611529 | 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
GCST007443_6	Nasal polyps	6.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): 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 — CYP2 family: physiological enzymes subset

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 466 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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	4
Benzo(a)pyrene	increases expression, affects cotreatment, increases oxidation, increases abundance	4
Tretinoin	affects metabolic processing, affects cotreatment, increases oxidation, increases metabolic processing, increases expression	4
bisphenol A	affects expression, decreases expression	3
Calcitriol	affects cotreatment, decreases expression, increases expression	3
Tobacco Smoke Pollution	increases expression	3
entinostat	increases expression, affects cotreatment	2
2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole	increases reduction, increases chemical synthesis, affects reaction	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
Air Pollutants	increases abundance, increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	2
Coal Tar	increases expression	2
Dioxins	increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Aflatoxin B1	increases expression, affects cotreatment, increases oxidation	2
aristolochic acid I	increases expression	1
PF-06840003	increases expression, decreases reaction	1
4-biphenylamine	increases reduction	1
cumene hydroperoxide	increases oxidation, increases abundance, affects cotreatment	1
flunisolide	decreases expression	1
2-aminofluorene	increases reduction	1
trichostatin A	decreases expression, decreases reaction	1
tris(2-butoxyethyl) phosphate	affects expression	1
benzo(a)pyrene-6,12-quinone	affects cotreatment, increases abundance, increases oxidation	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression	1
benzo(a)pyrene 7,8-dihydrodiol	affects cotreatment, increases oxidation, increases abundance	1
benzo(a)pyrene-3,6-quinone	increases abundance, increases oxidation, affects cotreatment	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
9,10-dihydrobenzo(a)pyrene	affects cotreatment, increases oxidation	1

ChEMBL screening assays

183 unique, capped per target: 181 admet, 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2060324	ADMET	Inhibition of CYP450	Rapid identification of ETP-46992, orally bioavailable PI3K inhibitor, selective versus mTOR. — Bioorg Med Chem Lett
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.