AOC3

Summary

AOC3 (amine oxidase copper containing 3, HGNC:550) is a protein-coding gene on chromosome 17q21.31, encoding Amine oxidase [copper-containing] 3 (Q16853). Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia.

This gene encodes a member of the semicarbazide-sensitive amine oxidase family. Copper amine oxidases catalyze the oxidative conversion of amines to aldehydes in the presence of copper and quinone cofactor. The encoded protein is localized to the cell surface, has adhesive properties as well as monoamine oxidase activity, and may be involved in leukocyte trafficking. Alterations in levels of the encoded protein may be associated with many diseases, including diabetes mellitus. A pseudogene of this gene has been described and is located approximately 9-kb downstream on the same chromosome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8639 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 155 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003734

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:550
Approved symbol	AOC3
Name	amine oxidase copper containing 3
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	VAP1, HPAO, VAP-1
Ensembl gene	ENSG00000131471
Ensembl biotype	protein_coding
OMIM	603735
Entrez	8639

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000308423, ENST00000587330, ENST00000588033, ENST00000591562, ENST00000592999, ENST00000613571, ENST00000617500

RefSeq mRNA: 3 — MANE Select: NM_003734 NM_001277731, NM_001277732, NM_003734

CCDS: CCDS11444, CCDS62198, CCDS74071

Canonical transcript exons

ENST00000308423 — 4 exons

Exon	Start	End
ENSE00002926158	42856275	42858124
ENSE00003480249	42855444	42855573
ENSE00003523064	42854448	42854733
ENSE00003844570	42851199	42852943

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 99.30.

FANTOM5 (CAGE): breadth broad, TPM avg 16.2015 / max 1216.7678, expressed in 286 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161013	14.5484	276
161014	0.4694	83
161022	0.3787	94
161015	0.2573	53
161019	0.1332	63
161021	0.1184	45
161016	0.0827	26
161017	0.0750	23
161020	0.0648	24
161012	0.0340	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	99.30	gold quality
saphenous vein	UBERON:0007318	99.21	gold quality
superficial temporal artery	UBERON:0001614	99.16	gold quality
right lung	UBERON:0002167	99.11	gold quality
popliteal artery	UBERON:0002250	99.09	gold quality
tibial artery	UBERON:0007610	99.09	gold quality
right coronary artery	UBERON:0001625	99.07	gold quality
aorta	UBERON:0000947	98.99	gold quality
left coronary artery	UBERON:0001626	98.99	gold quality
coronary artery	UBERON:0001621	98.96	gold quality
descending thoracic aorta	UBERON:0002345	98.89	gold quality
lower lobe of lung	UBERON:0008949	98.89	gold quality
ascending aorta	UBERON:0001496	98.85	gold quality
thoracic aorta	UBERON:0001515	98.85	gold quality
adipose tissue	UBERON:0001013	98.67	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.62	gold quality
upper lobe of left lung	UBERON:0008952	98.57	gold quality
upper lobe of lung	UBERON:0008948	98.53	gold quality
seminal vesicle	UBERON:0000998	98.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.30	gold quality
pericardium	UBERON:0002407	98.27	gold quality
lower esophagus	UBERON:0013473	98.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.19	gold quality
omental fat pad	UBERON:0010414	98.12	gold quality
peritoneum	UBERON:0002358	98.10	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.10	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.10	gold quality
colonic epithelium	UBERON:0000397	97.68	gold quality
connective tissue	UBERON:0002384	97.65	gold quality
vena cava	UBERON:0004087	97.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.28
E-HCAD-11	yes	7.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting AOC3, 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-5193	100.00	67.26	1744
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4267	99.96	66.53	2368
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-4717-3P	99.06	66.34	1072

Literature-anchored findings (GeneRIF, showing 40)

• VAP-1 is expressed on hepatic sinusoidal endothelial cells in vitro and supports adhesion and transmigration of lymphocytes across these cells under physiological shear stress. (PMID:12097405)
• Data show that increases in vascular adhesion protein-1 (VAP-1) due to absolute or relative insulin deficiency may be directly involved in the pathogenesis of diabetic angiopathy. (PMID:12466139)
• normal mice and human lungs revealed vascular adhesion protein-1 expression in the endothelium of large and mid-sized pulmonary vessels (PMID:12700900)
• may convert endogenous amines, like methylamine, to vasoactive metabolites. (PMID:14715500)
• the oxidase activity of VAP-1 controls PMN exit from the blood during the relatively poorly understood transmigration step (PMID:14726375)
• Semicarbazide-sensitive amine oxidase is a source of oxidative stress in diseased human skeletal muscle; it contributes to oxidative stress-induced damage in various inflammatory and other myopathies. (PMID:14755492)
• VAP-1 protein expression is significantly decreased in intratumoral vessels compared with peritumoral ones; this difference was independent of the skin melanoma thickness (PMID:15057044)
• Plasma semicarbazide-sensitive amine oxidase (SSAO) is elevated in patients with type 1 and type 2 diabetes and has been implicated in the pathophysiology of diabetic late complications. (PMID:15830186)
• results suggest that vascular adhesion protein-1 (VAP-1) levels are correlated with fasting glucose and insulin in morbidly obese subjects, and after surgery VAP-1 levels were associated with changes in visceral adiposity and diastolic blood pressure (PMID:15919838)
• The dimer structure reveals intriguing features that may have fundamental roles in the adhesive and enzymatic functions of hVAP-1. (PMID:16046623)
• This study indicates the important role of VAP-1 in the pathogenesis of chronic inflammatory cutaneous disorders, including AE. (PMID:16361866)
• A role for AOC3-mediated deamination in pulmonary inflammation was shown. (PMID:16507887)
• Tetragonal crystals were obtained and a data set extending to 2.5 A was collected. The crystals are merohedrally twinned and the estimate of the twinning fraction was complicated by pseudo-symmetry of the crystals. (PMID:16511016)
• VAP-1 may contribute critically to the oxidase activities in utero, and prove important for lymphocyte trafficking during human ontogeny. (PMID:16556889)
• We propose that VAP-1 might participate in controlling leukocyte entry into inflamed brain. (PMID:16806498)
• Expression of VAP-1, Stabilin-1, L-SIGN can be used to identify sinusoidal endothelium and to permit discrimination from vascular and lymphatic endothelial cells. (PMID:17006978)
• We propose that as well as directly promoting adhesion via interactions with the as yet unknown ligand, binding of enzyme substrate to VAP-1 can indirectly promote inflammatory cell recruitment via upregulation of adhesion molecules and chemokines. (PMID:17256751)
• Taken together, these results allow us to postulate that SSAO may contribute to the vascular damage associated to AD. (PMID:17393059)
• VAP-1 was located solely in the membrane fraction of the vascular smooth muscle cell. However it was also shown to be released into the cell-culture medium. (PMID:17393062)
• semicarbazide-sensitive amine oxidase expression during in vitro differentiation of human preadipocytes and in adipose and stroma-vascular fractions of human fat depots (PMID:17400359)
• The elevated serum SSAO activity measured through the detection of the enzyme-generated hydrogen peroxide in HD patients might indicate its contribution to the accelerated atherosclerotic disease observed in uremia. (PMID:17431736)
• Data suggest atherosclerotic inflammation may be a trigger for sclerosis in calcified stenotic aortic valves through upregulation TGF-beta, VAP-1, MIG and Eotaxin3, which is only partially inhibited by previous statin therapy. (PMID:17490641)
• VAP-1 may aggravate ischaemic vascular changes and thhe subsequent release of VAP-1 into circulation could be further examined as a potential marker of early ischaemic vasculopathy. (PMID:18005095)
• Serum levels of VAP-1 are associated with the severity of kidney damage or stages of kidney disease. (PMID:18644360)
• Increase in the SSAO activity and nitrite and nitrite levels observed in type 2 diabetic patients could be parameters to take in account and play relevant role in diabetes development. (PMID:18853098)
• VAP-1 regulates the inflammatory response in ischemia-reperfusion injury and suggest that blockade of VAP-1 may have therapeutic value. (PMID:18991279)
• Serum VAP-1 is increased in both acute and chronic hyperglycemia. (PMID:19336232)
• acute change of serum SSAO/VAP-1 is a novel marker for hyperglycemia-induced atherosclerosis (PMID:19361461)
• immunohistochemistry reveals constitutive expression of VAP-1 in human ocular tissues. (PMID:19761765)
• Inflammation of the dental pulp was accompanied by a significant decrease in MAO labeling, MAO B (but not MAO A) activity and the increase in SSAO activity. (PMID:19789505)
• the Siglec-10-VAP-1 interaction seems to mediate lymphocyte adhesion to endothelium (PMID:19861682)
• The SSAO activity in the serum of patients with type 2 diabetes is higher when compared with control group and may be a useful marker for diabetes. (PMID:20063021)
• A novel combination of surface molecules, including VAP-1 and CX(3)CL1 promotes the recruitment of CD16(+) monocytes to the liver, allowing them to localize at sites of chronic inflammation and fibrosis. (PMID:20512991)
• These remarks suggest that MAO-A and SSAO may play an important role in vascular tissue as well as in the vascular pathophysiology of type 2 diabetes. (PMID:21114364)
• The structure of VAP-1 was refined to a resolution of 2.9A. (PMID:21139198)
• Serum VAP-1 can predict 10-year all-cause mortality, cardiovascular mortality, and cancer mortality independently in type 2 diabetic subjects. (PMID:21282368)
• This review examines the biological functions of VAP-1, especially the role that this molecule might play in the establishment and progression of chronic liver disease. (PMID:21512782)
• Met211 and Leu469 were shown to be key residues for substrate specificity. (PMID:21585208)
• using an endothelial cell model, a description for the first time the involvement of the leucocyte-adhesion activity of SSAO/VAP-1 in the Abeta (amyloid beta-peptide)-mediated pro-inflammatory effect (PMID:21819380)
• The Siglec-9 peptide binding to the enzymatic groove of VAP-1 can be used for imaging conditions, such as inflammation and cancer. (PMID:21821708)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	aoc2	ENSDARG00000014646
mus_musculus	Aoc3	ENSMUSG00000019326

Paralogs (2): AOC1 (ENSG00000002726), AOC2 (ENSG00000131480)

Protein

Protein identifiers

Amine oxidase [copper-containing] 3 — Q16853 (reviewed: Q16853)

Alternative names: Amine oxidase copper-containing 3, Copper amine oxidase, HPAO, Semicarbazide-sensitive amine oxidase, Vascular adhesion protein 1

All UniProt accessions (4): Q16853, K7EIK5, K7EL47, K7EQZ5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia. Has a preference for the primary monoamines methylamine and benzylamine. Could also act on 2-phenylethylamine but much less efficiently. At endothelial cells surface can also function as a cell adhesion protein that participates in lymphocyte extravasation and recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. Has no semicarbazide-sensitive amine oxidase (SSAO) activity.

Subunit / interactions. Homodimer; disulfide-linked. Can heterodimerize with isoform 2 leading to reduced surface expression. Probably forms heterodimers with AOC2.

Subcellular location. Cell membrane.

Tissue specificity. Strongly expressed on the high endothelial venules of peripheral lymph nodes and on hepatic endothelia. Also highly expressed in appendix, lung and small intestine. Expressed also in adipose tissue, in bone marrow, colon, heart, kidney, ovary, pancreas, placenta, prostate, skeletal muscle, spleen and testis. Isoform 2 seems to be the predominant transcript in fetal kidneys, fetal cartilage and fetal tonsils. The highest relative expression of isoform 2 occurs in skeletal muscle, heart, pancreas, kidney, and lung.

Post-translational modifications. Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue. N- and O-glycosylated.

Cofactor. Binds 1 copper ion per subunit. Binds 2 calcium ions per subunit. Contains 1 topaquinone per subunit.

Induction. Up-regulated during in vitro adipocyte differentiation.

Miscellaneous. Dubious isoform lacking the transmembrane domain and active sites and is therefore most probably catalytically inactive.

Similarity. Belongs to the copper/topaquinone oxidase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q16853-1	1	yes
Q16853-2	2, VAP-1Delta3
Q16853-3	3

RefSeq proteins (3): NP_001264660, NP_001264661, NP_003725* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000269	Cu_amine_oxidase	Family
IPR015798	Cu_amine_oxidase_C	Domain
IPR015800	Cu_amine_oxidase_N2	Domain
IPR015802	Cu_amine_oxidase_N3	Domain
IPR016182	Cu_amine_oxidase_N-reg	Homologous_superfamily
IPR036460	Cu_amine_oxidase_C_sf	Homologous_superfamily
IPR049947	Cu_Am_Ox_Cu-bd	Conserved_site
IPR049948	Cu_Am_ox_TPQ-bd	Conserved_site

Pfam: PF01179, PF02727, PF02728

Enzyme classification (BRENDA):

• EC 1.4.3.21 — primary-amine oxidase (BRENDA: 28 organisms, 170 substrates, 291 inhibitors, 129 Km, 92 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
BENZYLAMINE	0.0013–2.38	24
2-PHENYLETHYLAMINE	0.0012–1.94	14
METHYLAMINE	0.01–2.043	13
BETA-PHENYLETHYLAMINE	0.0009–0.028	11
TYRAMINE	0.0104–1.92	8
O2	0.0163–1	6
HISTAMINE	0.28–0.88	4
PUTRESCINE	0.038–1.2	4
AMYLAMINE	0.11–5.71	3
BUTYLAMINE	0.32–2.83	3
CADAVERINE	0.089–12.7	3
HEXAKIS(BENZYLAMMONIUM) DECAVANADATE (V) DIHYDRA	0.014–0.213	3
SPERMIDINE	0.348–7.04	3
DOPAMINE	0.099–0.1	2
ETHYLAMINE	0.86–12.8	2

Catalyzed reactions (Rhea), 3 shown:

• 2-phenylethylamine + O2 + H2O = 2-phenylacetaldehyde + H2O2 + NH4(+) (RHEA:25265)
• methylamine + O2 + H2O = formaldehyde + H2O2 + NH4(+) (RHEA:59420)
• benzylamine + O2 + H2O = benzaldehyde + H2O2 + NH4(+) (RHEA:59424)

UniProt features (125 total): strand 43, helix 20, sequence variant 14, binding site 13, turn 9, glycosylation site 9, disulfide bond 4, splice variant 3, mutagenesis site 3, topological domain 2, active site 2, chain 1, modified residue 1, transmembrane region 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2C10	X-RAY DIFFRACTION	2.5
2Y73	X-RAY DIFFRACTION	2.6
4BTX	X-RAY DIFFRACTION	2.78
4BTW	X-RAY DIFFRACTION	2.8
1US1	X-RAY DIFFRACTION	2.9
2C11	X-RAY DIFFRACTION	2.9
3ALA	X-RAY DIFFRACTION	2.9
2Y74	X-RAY DIFFRACTION	2.95
4BTY	X-RAY DIFFRACTION	3.1
1PU4	X-RAY DIFFRACTION	3.2
8S1Z	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16853-F1	95.15	0.92

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 386 (proton acceptor); 471 (schiff-base intermediate with substrate; via topaquinone)

Ligand- & substrate-binding residues (13): 531; 572; 641; 663; 665; 667; 673; 674; 684; 520; 522; 529 …

Post-translational modifications (1): 471

Disulfide bonds (4): 198–199, 404–430, 734–741, 748

Glycosylation sites (9): 43, 137, 212, 232, 294, 592, 618, 666, 679

Mutagenesis-validated functional residues (3):

Position	Phenotype
211	increased activity towards 2-phenylethylamine, and decreased activity towards methylamine and benzylamine; when associat
394	increased activity towards 2-phenylethylamine, and decreased activity towards methylamine and benzylamine; when associat
469	increased activity towards 2-phenylethylamine, and decreased activity towards methylamine and benzylamine; when associat

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-1430728	Metabolism
R-HSA-211859	Biological oxidations

MSigDB gene sets: 141 (showing top): MODULE_93, REACTOME_BIOLOGICAL_OXIDATIONS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_INFLAMMATORY_RESPONSE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOCC_CELL_SURFACE, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, SRF_C, INGRAM_SHH_TARGETS_DN, DELYS_THYROID_CANCER_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, TSENG_IRS1_TARGETS_DN, MODULE_373, NAKAYAMA_SOFT_TISSUE_TUMORS_PCA2_DN, SABATES_COLORECTAL_ADENOMA_DN

GO Biological Process (3): inflammatory response (GO:0006954), cell adhesion (GO:0007155), amine metabolic process (GO:0009308)

GO Molecular Function (9): copper ion binding (GO:0005507), calcium ion binding (GO:0005509), primary methylamine oxidase activity (GO:0008131), identical protein binding (GO:0042802), protein heterodimerization activity (GO:0046982), quinone binding (GO:0048038), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (8): cytoplasm (GO:0005737), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), microvillus (GO:0005902), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
defense response	1
cellular process	1
metabolic process	1
transition metal ion binding	1
metal ion binding	1
oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor	1
protein binding	1
protein dimerization activity	1
small molecule binding	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
endosome	1
membrane	1
cell periphery	1
actin filament bundle	1
actin-based cell projection	1

Protein interactions and networks

STRING

2290 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AOC3	SIGLEC9	Q9Y336	977
AOC3	SIGLEC10	Q96LC7	891
AOC3	PTPRC	P08575	878
AOC3	CD4	P01730	873
AOC3	ITGAM	P11215	850
AOC3	CD3E	P07766	844
AOC3	CD8A	P01732	840
AOC3	ITGAX	P20702	840
AOC3	ITGAL	P20701	837
AOC3	CD19	P15391	795
AOC3	SELL	P14151	791
AOC3	FCGR3B	O75015	790
AOC3	FCGR3A	P08637	790
AOC3	FOXP3	Q9BZS1	783
AOC3	IFNG	P01579	776

IntAct

38 interactions, top by confidence:

A	B	Type	Score
AOC3	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
STX1A	AOC3	psi-mi:“MI:0915”(physical association)	0.560
SGTA	AOC3	psi-mi:“MI:0915”(physical association)	0.560
AOC3	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
AOC3	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	AOC3	psi-mi:“MI:0915”(physical association)	0.560
AOC3	FNDC9	psi-mi:“MI:0915”(physical association)	0.560
AOC3	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
AOC3	DARS2	psi-mi:“MI:0915”(physical association)	0.560
HTT	AOC3	psi-mi:“MI:0915”(physical association)	0.560
AOC3	AOC2	psi-mi:“MI:0914”(association)	0.530
AOC3	PRRG4	psi-mi:“MI:0915”(physical association)	0.370
TEX101	PSMD12	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
CTNNA1	ILVBL	psi-mi:“MI:0914”(association)	0.350
AOC3	STX1A	psi-mi:“MI:0915”(physical association)	0.000
AOC3	SGTA	psi-mi:“MI:0915”(physical association)	0.000
AOC3	CREB3L1	psi-mi:“MI:0915”(physical association)	0.000
AOC3	CLDN9	psi-mi:“MI:0915”(physical association)	0.000
AOC3	FNDC9	psi-mi:“MI:0915”(physical association)	0.000
AOC3	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
AOC3	CPLX4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (44): AOC2 (Affinity Capture-MS), EXTL2 (Affinity Capture-MS), SLC9A1 (Affinity Capture-MS), MANEA (Affinity Capture-MS), ERF (Affinity Capture-MS), ARL6IP6 (Affinity Capture-MS), AOC3 (Two-hybrid), NAGK (Negative Genetic), PIK3C2B (Negative Genetic), NDUFA4L2 (Negative Genetic), PIK3CD (Negative Genetic), PIK3R2 (Negative Genetic), SLC16A8 (Negative Genetic), CYP11B2 (Negative Genetic), TYK2 (Negative Genetic)

ESM2 similar proteins: O00115, O08590, O15547, O46406, O62855, O70423, O95897, P10820, P14222, P34387, P35763, P36633, P56541, P56542, Q04912, Q16853, Q17778, Q24K15, Q29437, Q2KJC3, Q2T8B0, Q3JJK4, Q3V5L5, Q4R9E0, Q5R9I0, Q5SSH8, Q62190, Q63IT3, Q6AX53, Q6NUS6, Q6TMA8, Q71SY6, Q75WF2, Q765H6, Q812C9, Q8JZQ5, Q8R2Q6, Q8WZ79, Q91ZV7, Q93086

Diamond homologs: H2A0M3, O08590, O46406, O70423, O75106, P19801, P36633, Q16853, Q29437, Q5R9I0, Q812C9, Q8JZQ5, Q9TRC7, Q9TTK6, O23349

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	129
Likely benign	17
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

992 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42852943:GGTAA:G	donor_loss	1.0000
17:42852944:GTAAG:G	donor_loss	1.0000
17:42852945:T:A	donor_loss	1.0000
17:42854731:GAG:G	donor_gain	1.0000
17:42854734:GTG:G	donor_loss	1.0000
17:42855570:A:T	donor_gain	1.0000
17:42855571:AAGGT:A	donor_loss	1.0000
17:42855572:AGGTC:A	donor_loss	1.0000
17:42855574:GTCA:G	donor_loss	1.0000
17:42855575:T:G	donor_loss	1.0000
17:42855590:AGAG:A	donor_gain	1.0000
17:42855591:GAGG:G	donor_gain	1.0000
17:42852940:GCAG:G	donor_gain	0.9900
17:42854493:T:TA	acceptor_gain	0.9900
17:42854729:GAGAG:G	donor_gain	0.9900
17:42854732:AG:A	donor_gain	0.9900
17:42854733:GG:G	donor_gain	0.9900
17:42854734:G:GG	donor_gain	0.9900
17:42854735:T:G	donor_loss	0.9900
17:42856272:TA:T	acceptor_loss	0.9900
17:42856273:AG:A	acceptor_gain	0.9900
17:42856274:GG:G	acceptor_gain	0.9900
17:42852944:G:GG	donor_gain	0.9800
17:42853249:ATG:A	acceptor_gain	0.9800
17:42854441:T:TA	acceptor_gain	0.9800
17:42855569:G:GT	donor_gain	0.9800
17:42856269:T:TA	acceptor_gain	0.9800
17:42856273:A:AG	acceptor_gain	0.9800
17:42856274:G:GG	acceptor_gain	0.9800
17:42853999:T:TA	acceptor_gain	0.9700

AlphaMissense

4971 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42852637:T:C	F432L	0.987
17:42852639:T:A	F432L	0.987
17:42852639:T:G	F432L	0.987
17:42855487:A:C	S644R	0.982
17:42855489:C:A	S644R	0.982
17:42855489:C:G	S644R	0.982
17:42856287:T:A	W677R	0.980
17:42856287:T:C	W677R	0.980
17:42851661:G:C	K106N	0.975
17:42851661:G:T	K106N	0.975
17:42852633:T:G	C430W	0.971
17:42852638:T:G	F432C	0.970
17:42856289:G:C	W677C	0.968
17:42856289:G:T	W677C	0.968
17:42852346:T:A	W335R	0.967
17:42852346:T:C	W335R	0.967
17:42852924:G:C	K527N	0.967
17:42852924:G:T	K527N	0.967
17:42852555:C:G	C404W	0.966
17:42852632:G:A	C430Y	0.966
17:42852118:T:A	W259R	0.963
17:42852118:T:C	W259R	0.963
17:42852554:G:A	C404Y	0.963
17:42852553:T:A	C404S	0.961
17:42852553:T:C	C404R	0.961
17:42852554:G:C	C404S	0.961
17:42852631:T:C	C430R	0.957
17:42852766:T:A	W475R	0.956
17:42852766:T:C	W475R	0.956
17:42854654:T:G	Y603D	0.956

dbSNP variants (sampled 300 via entrez): RS1000593995 (17:42853438 C>T), RS1000740172 (17:42851365 G>A), RS1001408836 (17:42853692 C>G), RS1002213011 (17:42849205 C>T), RS1002472101 (17:42854792 G>A,C), RS1003587916 (17:42857557 C>A,G), RS1003704430 (17:42857762 C>G), RS1004709673 (17:42855941 G>A), RS1004808707 (17:42853031 G>A), RS1005204149 (17:42853321 T>C,G), RS1005383899 (17:42858525 C>T), RS1005865276 (17:42856141 T>C,G), RS1006471150 (17:42854759 G>A,C), RS1006959697 (17:42855805 T>G), RS1007177120 (17:42854008 C>T)

Disease associations

OMIM: gene MIM:603735 | 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 (1): CHEMBL3437 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 18,877 (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
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL489079	MOFEGILINE	2	84

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 1.-.-.- Oxidoreductases

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
timolumab	Binding	9.89	pKd
PXS-4728A	Inhibition	8.3	pIC50
mofegiline	Inhibition	7.74	pIC50
phenelzine	Inhibition	7.7	pIC50
PXS-4681A	Irreversible inhibition	7.43	pKi

Binding affinities (BindingDB)

210 measured of 301 human assays (301 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[3-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]phenyl]methyl N-aminocarbamate	IC50	0.5 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
1-[[3-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]phenyl]methyl]-3-aminourea	IC50	0.7 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
[4-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]phenyl]methyl N-aminocarbamate	IC50	0.9 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
[4-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]-3-fluorophenyl]methyl N-aminocarbamate	IC50	0.9 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
2-[6-[(Z)-2-(aminomethyl)-3-fluoro-allyloxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]-N,N-dimethyl-acetamide hydrochloride	IC50	1 nM	US-12258317: Isoquinolinone compound for inhibiting ssao/vap-1, and use thereof
1-[[4-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]-3-fluorophenyl]methyl]-3-aminourea	IC50	2 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
[4-cyano-3-[4-(3-cyanophenyl)piperazin-1-yl]-2-fluorophenyl]methyl N-(diaminomethylidene)carbamate	IC50	2 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
3-[4-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]thiophen-2-yl]propanehydrazide	IC50	2.2 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
2-[6-[(Z)-2-(aminomethyl)-3-fluoro-allyloxy]-1-oxo-3,4-dihydroisoquinolin-2-yl] acetamide hydrochloride	IC50	2.2 nM	US-12258317: Isoquinolinone compound for inhibiting ssao/vap-1, and use thereof
1-[4-(cyanomethyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]piperidin-4-yl]-3-[(2-fluoro-4-pyridinyl)amino]pyrazole-4-carboxamide	IC50	2.7 nM	US-9556160: Guanidine compound
[4-cyano-3-[4-(4-cyanophenyl)piperazin-1-yl]-2-fluorophenyl]methyl N-(diaminomethylidene)carbamate	IC50	3 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
[4-cyano-2-fluoro-3-[4-(2-methyl-4-pyridinyl)piperazin-1-yl]phenyl]methyl N-(diaminomethylidene)carbamate	IC50	3 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
2-[4-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]phenyl]acetohydrazide	IC50	3.2 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
6-[(E)-2-(aminomethyl)-3-fluoro-allyloxy]-2-(2-methylsulfonylethyl)-3,4-dihydroisoquinoline-1-one hydrochloride	IC50	3.38 nM	US-12258317: Isoquinolinone compound for inhibiting ssao/vap-1, and use thereof
3-anilino-1-[4-(cyanomethyl)-1-(2,2-diphenylacetyl)piperidin-4-yl]pyrazole-4-carboxamide	IC50	3.4 nM	US-9556160: Guanidine compound
2-[4-[2-[5-(4-acetylpiperazin-1-yl)pyrazin-2-yl]ethyl]phenyl]acetohydrazide	IC50	3.4 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
[4-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]phenyl] N-aminocarbamate	IC50	3.5 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
6-[(E)-2-(aminomethyl)-3-fluoro-allyloxy]-2-(2-diethoxyphosphorylethyl)-3,4-dihydroisoquinoline-1-one hydrochloride	IC50	3.67 nM	US-12258317: Isoquinolinone compound for inhibiting ssao/vap-1, and use thereof
1-[[4-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]phenyl]methyl]-3-aminourea	IC50	3.7 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
2-[5-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]thiophen-2-yl]acetohydrazide	IC50	3.7 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
2-[6-[(Z)-2-(aminomethyl)-3-fluoro-allyloxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]-N-methyl-acetamide hydrochloride	IC50	3.7 nM	US-12258317: Isoquinolinone compound for inhibiting ssao/vap-1, and use thereof
2-[5-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]thiophen-2-yl]ethyl N-aminocarbamate	IC50	4 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
[3-[4-(1-acetylpiperidin-4-yl)piperidin-1-yl]-4-cyano-2-fluorophenyl]methyl N-(diaminomethylidene)carbamate	IC50	4 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
methyl 4-[1-[6-cyano-3-(diaminomethylidenecarbamoyloxymethyl)-2-fluorophenyl]piperidin-4-yl]piperidine-1-carboxylate	IC50	4 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
4-[1-[6-cyano-3-(diaminomethylidenecarbamoyloxymethyl)-2-fluorophenyl]piperidin-4-yl]benzoic acid	IC50	4 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
2-[6-[(E)-2-(aminomethyl)-3-fluoro-allyloxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]-N-(3,3-difluorocyclobutyl)-acetamide hydrochloride	IC50	4.01 nM	US-12258317: Isoquinolinone compound for inhibiting ssao/vap-1, and use thereof
2-[6-[(Z)-2-(aminomethyl)-3-fluoro-allyloxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]-N-ethyl-acetamide hydrochloride	IC50	4.12 nM	US-12258317: Isoquinolinone compound for inhibiting ssao/vap-1, and use thereof
1-[4-(cyanomethyl)-1-(2,2-difluorobutanoyl)piperidin-4-yl]-3-[(2-fluoro-4-pyridinyl)amino]pyrazole-4-carboxamide	IC50	4.3 nM	US-9556160: Guanidine compound
3-[4-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]phenyl]propanehydrazide	IC50	4.7 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
3-[4-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]thiophen-2-yl]propyl N-aminocarbamate	IC50	4.7 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
[4-cyano-2-fluoro-3-(4-pyridazin-4-ylpiperazin-1-yl)phenyl]methyl N-(diaminomethylidene)carbamate	IC50	5 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
[4-cyano-2-fluoro-3-[4-(1-methylsulfonylpiperidin-4-yl)piperidin-1-yl]phenyl]methyl N-(diaminomethylidene)carbamate	IC50	5 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
[4-cyano-3-[4-(3-cyanophenyl)piperidin-1-yl]-2-fluorophenyl]methyl N-(diaminomethylidene)carbamate	IC50	5 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
[4-cyano-2-fluoro-3-(4-imidazo[1,2-a]pyridin-2-ylpiperidin-1-yl)phenyl]methyl N-(diaminomethylidene)carbamate	IC50	5 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
[4-cyano-2-fluoro-3-[4-(4-fluorophenyl)-3-oxopiperazin-1-yl]phenyl]methyl N-(diaminomethylidene)carbamate	IC50	5 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
3-anilino-1-[4-(cyanomethyl)-1-[2-[4-(trifluoromethyl)phenyl]acetyl]piperidin-4-yl]pyrazole-4-carboxamide	IC50	5.2 nM	US-9556160: Guanidine compound
3-anilino-1-[4-(cyanomethyl)-1-[4-(4-methylpiperazin-1-yl)benzoyl]piperidin-4-yl]pyrazole-4-carboxamide	IC50	5.3 nM	US-9556160: Guanidine compound
[4-cyano-2-fluoro-3-[4-(4-methylsulfonylphenyl)piperazin-1-yl]phenyl]methyl N-(diaminomethylidene)carbamate	IC50	6 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
[4-cyano-2-fluoro-3-(4-pyridin-3-ylpiperazin-1-yl)phenyl]methyl N-(diaminomethylidene)carbamate	IC50	6 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
[3-[4-(4-chlorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-4-cyano-2-fluorophenyl]methyl N-(diaminomethylidene)carbamate	IC50	6 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
2-[6-[(E)-2-(aminomethyl)-3-fluoroprop-2-enoxy]-1-oxo-3,4-dihydroisoquinolin-2-yl]acetamide	IC50	6.29 nM	US-12258317: Isoquinolinone compound for inhibiting ssao/vap-1, and use thereof
3-anilino-1-[1-(2-cyanoacetyl)-4-(cyanomethyl)piperidin-4-yl]pyrazole-4-carboxamide	IC50	6.3 nM	US-9556160: Guanidine compound
2-[4-[2-(2-piperazin-1-yl-1,3-thiazol-4-yl)ethyl]phenyl]acetohydrazide	IC50	6.3 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
2-[4-[2-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]ethyl]phenyl]ethyl N-aminocarbamate	IC50	6.6 nM	US-9603833: Benzene or thiophene derivative and use thereof as VAP-1 inhibitor
(E)-3-[6-[4-[5-[3-[[(2-aminoacetyl)-methylamino]methyl]phenyl]pyrimidin-2-yl]piperazin-1-yl]-5-methyl-3-pyridinyl]prop-2-enoic acid	IC50	6.9 nM	US-8802679: Glycine compound
2-amino-N-methyl-N-[[3-[2-(4-pyridin-3-yl-3,6-dihydro-2H-pyridin-1-yl)pyrimidin-5-yl]phenyl]methyl]acetamide	IC50	7 nM	US-8802679: Glycine compound
[4-cyano-2-fluoro-3-(4-pyrimidin-4-ylpiperazin-1-yl)phenyl]methyl N-(diaminomethylidene)carbamate	IC50	7 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
[3-[4-(5-chloro-2-pyridinyl)piperazin-1-yl]-4-cyano-2-fluorophenyl]methyl N-(diaminomethylidene)carbamate	IC50	7 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
[4-cyano-2-fluoro-3-(4-pyridin-4-ylpiperazin-1-yl)phenyl]methyl N-(diaminomethylidene)carbamate	IC50	7 nM	US-10336729: 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as AOC3 inhibitors
3-anilino-1-[4-(cyanomethyl)-1-(4-morpholin-4-ylbenzoyl)piperidin-4-yl]pyrazole-4-carboxamide	IC50	7.2 nM	US-9556160: Guanidine compound

ChEMBL bioactivities

992 potent at pChembl≥5 of 1081 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	IC50	0.04	nM	CHEMBL5949667
10.05	IC50	0.09	nM	CHEMBL5930465
9.96	IC50	0.11	nM	CHEMBL6030001
9.85	IC50	0.14	nM	CHEMBL6053891
9.70	IC50	0.2	nM	CHEMBL6001768
9.70	IC50	0.2	nM	CHEMBL5884221
9.70	IC50	0.2	nM	CHEMBL6016570
9.70	IC50	0.2	nM	CHEMBL5977694
9.70	IC50	0.2	nM	CHEMBL5909558
9.70	IC50	0.2	nM	CHEMBL5774203
9.70	IC50	0.2	nM	CHEMBL6034455
9.70	IC50	0.2	nM	CHEMBL6058433
9.66	IC50	0.22	nM	CHEMBL5742801
9.66	IC50	0.22	nM	CHEMBL5778651
9.52	IC50	0.3	nM	CHEMBL5810939
9.52	IC50	0.3	nM	CHEMBL6010009
9.52	IC50	0.3	nM	CHEMBL6042185
9.52	IC50	0.3	nM	CHEMBL5769606
9.52	IC50	0.3	nM	CHEMBL5752011
9.52	IC50	0.3	nM	CHEMBL5879186
9.52	IC50	0.3	nM	CHEMBL5993055
9.52	IC50	0.3	nM	CHEMBL5801027
9.52	IC50	0.3	nM	CHEMBL5900558
9.52	IC50	0.3	nM	CHEMBL6027951
9.52	IC50	0.3	nM	CHEMBL6013600
9.52	IC50	0.3	nM	CHEMBL5889367
9.52	IC50	0.3	nM	CHEMBL6056233
9.52	IC50	0.3	nM	CHEMBL5811353
9.52	IC50	0.3	nM	CHEMBL5976788
9.52	IC50	0.3	nM	CHEMBL5886360
9.52	IC50	0.3	nM	CHEMBL5759074
9.52	IC50	0.3	nM	CHEMBL5761926
9.52	IC50	0.3	nM	CHEMBL6013999
9.52	IC50	0.3	nM	CHEMBL6031782
9.52	IC50	0.3	nM	CHEMBL5779219
9.52	IC50	0.3	nM	CHEMBL5864694
9.49	IC50	0.32	nM	CHEMBL6008901
9.43	IC50	0.37	nM	CHEMBL5850337
9.40	IC50	0.4	nM	CHEMBL5990582
9.40	IC50	0.4	nM	CHEMBL5999329
9.40	IC50	0.4	nM	CHEMBL6026682
9.40	IC50	0.4	nM	CHEMBL5832926
9.40	IC50	0.4	nM	CHEMBL5828586
9.40	IC50	0.4	nM	CHEMBL6048376
9.40	IC50	0.4	nM	CHEMBL5744052
9.40	IC50	0.4	nM	CHEMBL5815932
9.40	IC50	0.4	nM	CHEMBL5740442
9.40	IC50	0.4	nM	CHEMBL5830578
9.40	IC50	0.4	nM	CHEMBL5789816
9.40	IC50	0.4	nM	CHEMBL5841363

PubChem BioAssay actives

193 with measured affinity, of 381 total; 50 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
4-[(E)-2-(aminomethyl)-3-fluoroprop-2-enoxy]-N-tert-butylbenzamide	2083434: Inhibition of human plasma VAP-1 using 6-(5-Pheny1-2H-tetrazol-2-yl)hexan-1-amine as substrate preincubated with enzyme for 15 mins followed by substrate addition measured after 120 mins by UV-HPLC analysis	ic50	0.0020	uM
4-[(E)-2-(aminomethyl)-3-fluoroprop-2-enoxy]-N-tert-butylbenzamide;hydrochloride	1330992: Inhibition of human recombinant VAP-1 using benzylamine as substrate incubated for 30 mins followed by substrate addition measured every 2.5 mins for 30 mins by fluorometric assay	ic50	0.0050	uM
[2-fluoro-3-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]methyl N-(diaminomethylidene)carbamate;hydrochloride	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0092	uM
4-[(E)-4-amino-2-fluorobut-2-enoxy]-N-cyclohexylbenzamide	662699: Inhibition of human recombinant SSAO/VAP1 assessed as H2O2 production by Resorufin/Amplex Red assay	ic50	0.0100	uM
[3-(4-pyridin-4-ylpiperazin-1-yl)phenyl]methyl N-(diaminomethylidene)carbamate;trihydrochloride	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0130	uM
(2R,3R)-2,3-dihydroxybutanedioic acid;[2-fluoro-3-(4-pyridin-3-ylpiperazin-1-yl)phenyl]methyl N-(diaminomethylidene)carbamate	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0170	uM
N-[4-[2-[4-[(2-amino-1H-imidazol-5-yl)methyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide;hydrochloride	753430: Inhibition of human VAP-1 expressed in CHO cells using [14C]-benzylamine as substrate preincubated for 30 mins prior to substrate addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0190	uM
Phenelzine	512126: Inhibition of human recombinant VAP-1 expressed in CHO cells after 30 mins by coupled colorimetric method	ic50	0.0199	uM
N-[4-[2-[4-(diaminomethylideneamino)phenyl]ethyl]-5-[(4-methylsulfonylphenyl)methyl]-1,3-thiazol-2-yl]acetamide	745009: Inhibition of human VAP1 expressed in CHO cells using [14C]-benzylamine as substrate incubated for 30 mins prior to substrate addition measured after 1 hr by scintillation counting analysis	ic50	0.0200	uM
1,2-dihydropyridazine-3,6-dione	1157003: Inhibition of human VAP1	ic50	0.0200	uM
4-[(E)-4-amino-2-fluorobut-2-enoxy]-N-cyclopentylbenzamide	662699: Inhibition of human recombinant SSAO/VAP1 assessed as H2O2 production by Resorufin/Amplex Red assay	ic50	0.0200	uM
(E)-3-fluoro-4-(4-methylsulfanylphenoxy)but-2-en-1-amine	662699: Inhibition of human recombinant SSAO/VAP1 assessed as H2O2 production by Resorufin/Amplex Red assay	ic50	0.0200	uM
4-(aminomethyl)-3-N,5-N-diethyl-3-N-methylpyridine-3,5-diamine;dihydrochloride	242475: Inhibition of benzylamine binding to Benzylamine oxidase of porcine serum	ic50	0.0200	uM
(2E)-2-(fluoromethylidene)-4-(4-fluorophenyl)butan-1-amine	662699: Inhibition of human recombinant SSAO/VAP1 assessed as H2O2 production by Resorufin/Amplex Red assay	ic50	0.0200	uM
2-(4-chlorophenyl)-5-[4-(4-methylpiperazin-1-yl)anilino]-6-(1H-1,2,4-triazol-5-yl)pyridazin-3-one;hydrochloride	1065999: Inhibition of human recombinant VAP-1 transfected in CHO cells using 2,4-dichlorophenol/benzylamine as substrate incubated for 30 mins prior to benzylamine addition measured after 1 hr by spectrophotometry	ic50	0.0200	uM
4-[4-[5-[3-[[(2-aminoacetyl)-methylamino]methyl]phenyl]pyrimidin-2-yl]piperazin-1-yl]benzoic acid;dihydrochloride	1486258: Inhibition of human VAP-1 expressed in CHO cells using 14C-benzylamine as substrate preincubated for 20 mins followed by substrate addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0240	uM
(2R,3R)-2,3-dihydroxybutanedioic acid;bis([2-fluoro-3-(3-pyridin-3-yloxyazetidin-1-yl)phenyl]methyl N-(diaminomethylidene)carbamate)	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0240	uM
(2R,3R)-2,3-dihydroxybutanedioic acid;[2-fluoro-3-[3-[(6-methyl-3-pyridinyl)oxy]azetidin-1-yl]phenyl]methyl N-(diaminomethylidene)carbamate	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0250	uM
4-[4-[5-[3-[[(2-aminoacetyl)-methylamino]methyl]phenyl]pyrimidin-2-yl]piperazin-1-yl]-3-chlorobenzoic acid;dihydrochloride	1486258: Inhibition of human VAP-1 expressed in CHO cells using 14C-benzylamine as substrate preincubated for 20 mins followed by substrate addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0250	uM
2-hydrazinyl-1-(4-methoxyphenyl)ethanol	512126: Inhibition of human recombinant VAP-1 expressed in CHO cells after 30 mins by coupled colorimetric method	ic50	0.0288	uM
4-[(E)-4-amino-2-fluorobut-2-enoxy]-N-[(1R)-1-phenylethyl]benzamide	662699: Inhibition of human recombinant SSAO/VAP1 assessed as H2O2 production by Resorufin/Amplex Red assay	ic50	0.0300	uM
2-amino-N-methyl-N-[[3-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]methyl]acetamide;(2R,3R)-2,3-dihydroxybutanedioic acid	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0310	uM
[3-(4-pyridin-3-ylpiperazin-1-yl)phenyl]methyl N-(diaminomethylidene)carbamate;trihydrochloride	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0310	uM
(2R,3R)-2,3-dihydroxybutanedioic acid;2-[methyl-[[3-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]methyl]amino]acetamide	1486258: Inhibition of human VAP-1 expressed in CHO cells using 14C-benzylamine as substrate preincubated for 20 mins followed by substrate addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0310	uM
N-[4-[2-[4-(diaminomethylideneamino)phenyl]ethyl]-5-(4-methylsulfonylphenyl)-1,3-thiazol-2-yl]acetamide;hydrochloride	745009: Inhibition of human VAP1 expressed in CHO cells using [14C]-benzylamine as substrate incubated for 30 mins prior to substrate addition measured after 1 hr by scintillation counting analysis	ic50	0.0340	uM
N-[4-[2-[4-(diaminomethylideneamino)phenyl]ethyl]-5-[(3-methylsulfonylphenyl)methyl]-1,3-thiazol-2-yl]acetamide	745009: Inhibition of human VAP1 expressed in CHO cells using [14C]-benzylamine as substrate incubated for 30 mins prior to substrate addition measured after 1 hr by scintillation counting analysis	ic50	0.0360	uM
(2R,3R)-2,3-dihydroxybutanedioic acid;[2-fluoro-3-[3-[(2-methyl-3-pyridinyl)oxy]azetidin-1-yl]phenyl]methyl N-(diaminomethylidene)carbamate	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0400	uM
4-[(E)-4-amino-2-fluorobut-2-enoxy]-N-[(1S)-1-phenylethyl]benzamide	662699: Inhibition of human recombinant SSAO/VAP1 assessed as H2O2 production by Resorufin/Amplex Red assay	ic50	0.0400	uM
(E)-3-fluoro-4-[4-(trifluoromethyl)phenoxy]but-2-en-1-amine	662699: Inhibition of human recombinant SSAO/VAP1 assessed as H2O2 production by Resorufin/Amplex Red assay	ic50	0.0400	uM
(1R)-2-hydrazinyl-1-phenylethanol	592739: Inhibition of human recombinant VAP-1 expressed in CHO cells after 30 mins by coupled colorimetric method	ic50	0.0400	uM
4-[(E)-4-amino-2-fluorobut-2-enoxy]-N-(1-phenylethyl)benzamide	662699: Inhibition of human recombinant SSAO/VAP1 assessed as H2O2 production by Resorufin/Amplex Red assay	ic50	0.0400	uM
(2R,3R)-2,3-dihydroxybutanedioic acid;2-[[3-[2-[4-(2-hydroxyethyl)piperidin-1-yl]pyrimidin-5-yl]phenyl]methyl-methylamino]acetamide	1486258: Inhibition of human VAP-1 expressed in CHO cells using 14C-benzylamine as substrate preincubated for 20 mins followed by substrate addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0450	uM
(2R,3R)-2,3-dihydroxybutanedioic acid;[2-fluoro-3-(4-pyridin-3-yloxypiperidin-1-yl)phenyl]methyl N-(diaminomethylidene)carbamate	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0450	uM
(2R,3R)-2,3-dihydroxybutanedioic acid;[3-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]methyl N-(diaminomethylidene)carbamate	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0470	uM
4-[(E)-4-amino-2-fluorobut-2-enoxy]-N-[(1S)-1-phenylethyl]benzenesulfonamide;hydrochloride	1526679: Inhibition of recombinant human SSAO using benzylamine as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured every 2.5 mins for 30 mins by Amplex-Red oxidation assay	ic50	0.0501	uM
2-hydrazinyl-1-(3-methoxyphenyl)ethanol	512126: Inhibition of human recombinant VAP-1 expressed in CHO cells after 30 mins by coupled colorimetric method	ic50	0.0525	uM
N-[4-[2-[4-(diaminomethylideneamino)phenyl]ethyl]-5-[(4-sulfamoylphenyl)methyl]-1,3-thiazol-2-yl]acetamide;hydrochloride	745009: Inhibition of human VAP1 expressed in CHO cells using [14C]-benzylamine as substrate incubated for 30 mins prior to substrate addition measured after 1 hr by scintillation counting analysis	ic50	0.0530	uM
bis(N-(diaminomethylidene)-2-[3-[2-(2-morpholin-4-ylpyrimidin-5-yl)ethyl]phenyl]acetamide);(2R,3R)-2,3-dihydroxybutanedioic acid	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0540	uM
(2R,3R)-2,3-dihydroxybutanedioic acid;2-[methyl-[[3-(6-morpholin-4-yl-3-pyridinyl)phenyl]methyl]amino]acetamide	1486258: Inhibition of human VAP-1 expressed in CHO cells using 14C-benzylamine as substrate preincubated for 20 mins followed by substrate addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0550	uM
N-(diaminomethylidene)-2-[3-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]acetamide;(2R,3R)-2,3-dihydroxybutanedioic acid	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0560	uM
2-phenylpropylhydrazine	512126: Inhibition of human recombinant VAP-1 expressed in CHO cells after 30 mins by coupled colorimetric method	ic50	0.0589	uM
1-[2-(4-methoxyphenyl)ethyl]-1-methylhydrazine	512126: Inhibition of human recombinant VAP-1 expressed in CHO cells after 30 mins by coupled colorimetric method	ic50	0.0603	uM
2-hydrazinyl-1-phenylethanol	512126: Inhibition of human recombinant VAP-1 expressed in CHO cells after 30 mins by coupled colorimetric method	ic50	0.0646	uM
(E)-3-fluoro-4-(4-nitrophenoxy)but-2-en-1-amine	662699: Inhibition of human recombinant SSAO/VAP1 assessed as H2O2 production by Resorufin/Amplex Red assay	ic50	0.0700	uM
1-[2-(4-chlorophenyl)ethyl]-1-methylhydrazine	512126: Inhibition of human recombinant VAP-1 expressed in CHO cells after 30 mins by coupled colorimetric method	ic50	0.0708	uM
5-(cyclohexylamino)-2-phenyl-6-(1H-1,2,4-triazol-5-yl)pyridazin-3-one	1065999: Inhibition of human recombinant VAP-1 transfected in CHO cells using 2,4-dichlorophenol/benzylamine as substrate incubated for 30 mins prior to benzylamine addition measured after 1 hr by spectrophotometry	ic50	0.0710	uM
bis([2,4-difluoro-3-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]methyl N-(diaminomethylidene)carbamate);(2R,3R)-2,3-dihydroxybutanedioic acid	1465129: Inhibition of human VAP-1 expressed in CHO cells preincubated for 20 mins followed by [14C]-benzylamine addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0770	uM
1-ethyl-1-[2-(4-methoxyphenyl)ethyl]hydrazine	512126: Inhibition of human recombinant VAP-1 expressed in CHO cells after 30 mins by coupled colorimetric method	ic50	0.0794	uM
4-[(E)-4-amino-2-fluorobut-2-enoxy]-N-benzylbenzamide	662699: Inhibition of human recombinant SSAO/VAP1 assessed as H2O2 production by Resorufin/Amplex Red assay	ic50	0.0800	uM
N-[4-[3-[[(2-aminoacetyl)-methylamino]methyl]phenyl]phenyl]morpholine-4-carboxamide;oxalic acid	1330978: Inhibition of human VAP-1 expressed in CHO cells using 14C-benzylamine as substrate preincubated for 20 mins followed by substrate addition measured after 1 hr by scintillation spectrometric analysis	ic50	0.0830	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
Tobacco Smoke Pollution	increases expression, affects expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	2
Dexamethasone	increases expression, affects cotreatment	2
Formaldehyde	affects metabolic processing, increases expression	2
Quercetin	decreases expression	2
Silicon Dioxide	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
carbamylhydrazine	decreases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ochratoxin A	increases expression	1
ferrous chloride	increases expression	1
versicolorin A	increases expression	1
coumarin	decreases phosphorylation	1
benazol P	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	affects expression	1
bisphenol B	increases expression	1
N’-(2-phenylallyl)hydrazine	decreases activity	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, affects expression	1

ChEMBL screening assays

65 unique, capped per target: 60 binding, 4 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1247376	Binding	Inhibition of human recombinant VAP-1 expressed in CHO cells after 30 mins by coupled colorimetric method	Synthesis, in vitro activity, and three-dimensional quantitative structure-activity relationship of novel hydrazine inhibitors of human vascular adhesion protein-1. — J Med Chem
CHEMBL3225061	ADMET	Stability of the compound assessed as human full length SSAO-mediated drug metabolism expressed in CHO cells measured as compound remaining after 20 mins	Structure-based design, synthesis, and profiling of a -tryptase inhibitor with a spiro-piperidineamide scaffold, benzylamine P1 group, and a substituted indole P4 group — Medchemcomm
CHEMBL853855	Functional	Activity of human SSAO measured as hydrogen peroxide production at 1 mM relative to benzylamine oxidation	New efficient substrates for semicarbazide-sensitive amine oxidase/VAP-1 enzyme: analysis by SARs and computational docking. — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E8GQ	A7r5 hSSAO/VAP-1	Spontaneously immortalized cell line	Sex unspecified
CVCL_F1YD	HUAEC:SSAO clone 8	Finite cell line	Sex unspecified

Clinical trials (associated diseases)

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