LOXL2

Summary

LOXL2 (lysyl oxidase like 2, HGNC:6666) is a protein-coding gene on chromosome 8p21.3, encoding Lysyl oxidase homolog 2 (Q9Y4K0). Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine).

This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family.

Source: NCBI Gene 4017 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 179 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002318

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6666
Approved symbol	LOXL2
Name	lysyl oxidase like 2
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	WS9-14, LOR
Ensembl gene	ENSG00000134013
Ensembl biotype	protein_coding
OMIM	606663
Entrez	4017

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 17 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000389131, ENST00000518083, ENST00000518472, ENST00000518878, ENST00000519243, ENST00000519809, ENST00000520349, ENST00000520617, ENST00000520871, ENST00000520925, ENST00000522446, ENST00000523833, ENST00000524075, ENST00000524144, ENST00000524168, ENST00000879572, ENST00000879573, ENST00000879574, ENST00000879575, ENST00000879576, ENST00000924129, ENST00000924130, ENST00000969380, ENST00000969381

RefSeq mRNA: 1 — MANE Select: NM_002318 NM_002318

CCDS: CCDS34864

Canonical transcript exons

ENST00000389131 — 14 exons

Exon	Start	End
ENSE00000911520	23316949	23317114
ENSE00001108979	23302027	23302163
ENSE00001108983	23309668	23309911
ENSE00001108985	23303282	23303397
ENSE00001108989	23298836	23298947
ENSE00001299444	23296897	23298122
ENSE00001745331	23333401	23333623
ENSE00001770381	23340992	23341203
ENSE00002094197	23403954	23404120
ENSE00003466808	23322130	23322281
ENSE00003595219	23367997	23368434
ENSE00003675821	23328382	23328565
ENSE00003784338	23360090	23360265
ENSE00003786435	23319885	23320052

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 99.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 104.9748 / max 1914.7139, expressed in 1399 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92316	103.7806	1389
92314	0.4736	265
92315	0.4079	256
92312	0.2559	153
92318	0.0437	10
92317	0.0087	4
205123	0.0044	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.18	gold quality
cartilage tissue	UBERON:0002418	98.15	gold quality
tibia	UBERON:0000979	92.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.16	gold quality
adipose tissue	UBERON:0001013	88.80	gold quality
smooth muscle tissue	UBERON:0001135	88.68	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.66	gold quality
lower esophagus	UBERON:0013473	88.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.52	gold quality
connective tissue	UBERON:0002384	88.35	gold quality
periodontal ligament	UBERON:0008266	88.31	gold quality
placenta	UBERON:0001987	88.29	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.15	gold quality
decidua	UBERON:0002450	87.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.35	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.25	gold quality
colonic epithelium	UBERON:0000397	85.81	gold quality
omental fat pad	UBERON:0010414	85.80	gold quality
peritoneum	UBERON:0002358	85.73	gold quality
sural nerve	UBERON:0015488	84.99	gold quality
vermiform appendix	UBERON:0001154	84.95	gold quality
sigmoid colon	UBERON:0001159	84.95	gold quality
myometrium	UBERON:0001296	84.83	gold quality
skin of hip	UBERON:0001554	84.61	gold quality
tendon of biceps brachii	UBERON:0008188	84.19	gold quality
caecum	UBERON:0001153	83.99	gold quality
mucosa of stomach	UBERON:0001199	83.81	gold quality
left ovary	UBERON:0002119	83.29	gold quality
islet of Langerhans	UBERON:0000006	83.12	gold quality
ascending aorta	UBERON:0001496	82.81	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	33.07
E-GEOD-83139	yes	7.72
E-ANND-3	yes	6.09
E-CURD-112	yes	5.77
E-MTAB-6678	yes	4.11

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F5, FOXA1

miRNA regulators (miRDB)

66 targeting LOXL2, 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-29B-3P	100.00	73.18	1833
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4465	99.71	72.56	2096

Literature-anchored findings (GeneRIF, showing 40)

• LOR-1 promotes tumor fibrosis and tumor invasiveness simultaneously. (PMID:12670920)
• No reduction of LOXL2-mRNA levels was found in the malignantly transformed tissues from HNSCC. LOXL2 may play a role in malignant transformation. (PMID:12820424)
• The upregulation of Loxl2 in Wilson’s disease could perhaps be utilized for diagnostic purposes since their expression is up-regulated in hepatocytes even before the onset of fibrosis. (PMID:16023247)
• Lysyl-oxidase-like 2 interacts and cooperates with Snail to downregulate E-cadherin expression, and control epithelial-mesenchymal transitions and carcinoma progression. (PMID:16096638)
• We detected an empirically significant association with one SNP of LOXL2 in familial IA patients after adjustment for multiple testing [chi(2) = 10.23, empirical P = 0.023, OR (95% CI) = 1.49 (1.17. (PMID:17287949)
• High levels of LOXL2 are associated with squamous cell carcinomas (PMID:18559498)
• Increased mRNA expression during progression of colorectal cancer with liver metastases (PMID:18590575)
• Breast carcinoma effusions showed significantly higher LOXL2 and lower LOXL3 expression compared to primary carcinomas. (PMID:19015874)
• up-regulation in human colorectal cancer is correlated with upregulation of the TIMP-1 transcript (PMID:19383344)
• Report reciprocal regulation of LOX and LOXL2 expression during cell adhesion and terminal differentiation in epidermal keratinocytes. (PMID:19394199)
• LOXL2 overexpression, a frequent event in gastric carcinoma progression and may be a therapeutic target for preventing and treating metastases. (PMID:19625348)
• Expression of LOXL, LOXL2, LOXL3 and LOXL4 was not statistically associated with tumor location, stage, growth type, or differentiation status in colorectal adenocarcinomas (PMID:19724858)
• The improved response toward chemotherapy in LOLX2-silenced pancreatic cancer cells is possibly mediated by the transcription factor E2F5. (PMID:20012301)
• molecular pathway from hypoxia to cellular transformation includes up-regulation of HIF and subsequent transcriptional induction of LOX and LOXL2, which repress E-cadherin and induce epithelial to mesenchymal transition (PMID:20026874)
• FOXA1 induces not only KRT7 but also LOXL2 in a subset of poor prognostic esophageal squamous cell carcinomas with metastatic lymph nodes (PMID:20043065)
• The purified recombinant LOXL2 proteins, with or without the SRCR domains in the N-terminus, showed significant amine oxidase activity toward several different types of collagen and elastin in in vitro amine oxidase assays. (PMID:20306300)
• Antibody allosteric modulators of enzymatic function represent a novel drug development strategy and, in the context of LOXL2, suggest that inhibitors such as these might be useful therapeutics in oncology, fibrosis, and inflammation. (PMID:20439985)
• Data show that LOXL2 and RAMP3 are strongly coexpressed in human colon, breast, and gastric carcinomas but not in normal colon or gastric epithelial cells. (PMID:20802105)
• Analysis of a published microarray data set revealed that LOXL2 expression is correlated with metastasis and decreased survival in patients with aggressive breast cancer (PMID:21233336)
• Down-regulation of lysyl oxidase-like 2 is associated with disease progression in lung adenocarcinomas. (PMID:21519871)
• Breast carcinoma cell lines with basal-like phenotype show a specific cytoplasmic/perinuclear LOXL2 expression, and this subcellular distribution is significantly associated with distant metastatic incidence in basal-like breast carcinomas. (PMID:21732535)
• The human lysyl oxidase-like 2 gene does not confer increased genotypic risk for adolescent idiopathic scoliosis. (PMID:21740577)
• This study provides the first evidence for the role of LOXL2 in regulating angiogenesis through collagen IV scaffolding. (PMID:21835952)
• These results suggest that lysyl oxidase L2 exerts a critical effect on esophageal squamous cell carcinoma progression and can be a predictive marker of lymph node metastasis and outcome. (PMID:22204712)
• Up-regulation of CCL2, CCL26, IL6 and LOXL2 genes in cancer cells are part of the common effects of cancer-associated fibroblasts on hepatocellular carcinoma cells (PMID:22739041)
• Intracellular (perinuclear) expression of LOXL2 is associated with poor prognosis and distant metastasis of specific tumor types. [Review] (PMID:23030485)
• the N-glycan at Asn-644 of hLOXL2 enhances the solubility and stability of the LOX catalytic domain (PMID:23319596)
• TGF-beta1 induced injured MCL to express more LOXs than injured ACL (up to 1.85-fold in LOX, 2.21-fold in LOXL-1, 1.71-fold in LOXL-2, 2.52-fold in LOXL-3 and 3.32-fold in LOXL-4). (PMID:23357697)
• Data suggest that all members of LOX gene family (lysyl-oxidase [LOX]; lysyl oxidase-like proteins [LOXL1, LOXL2, LOXL3]) are over-expressed in bone marrow in primary myelofibrosis; LOX gene family is not detectable in normal bone marrow. (PMID:23494965)
• Sequence analysis of LOXL2, genes did not reveal any putative mutations for hyperostosis cranialis interna to chromosome 8p21 (PMID:23640157)
• negative regulator of odontogenic differentiation of dental pulp stem cells (PMID:23677379)
• Higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. (PMID:23933800)
• LOXL2 expression in normal epithelial cells can induce abnormal changes that resemble oncogenic transformation and cancer progression. (PMID:23971878)
• Findings reveal new insight into the mechanisms of fibroblast activation, a novel function of LOXL2, and further highlight the importance of generating LOXL2-targeted therapies for the prevention of tumor progression and metastasis. (PMID:24008674)
• nuclear associated LOXL2 contributes to the stabilization of Snail1 transcription factor at the protein level to induce EMT and promote invasion in vitro (PMID:24014025)
• higher sLOXL2 levels are associated with increased risk for IPF disease progression (PMID:24177001)
• These results provide important clues for experimental identification of the specific biological roles and molecular mechanisms of LOXL2-delta72. (PMID:24716982)
• LOXL2 activates the FAK/Akt/mTOR signaling pathways and promotes cell proliferation and inhibits apoptotic cell death. (PMID:24863880)
• promoted intrahepatic metastasis by increasing tissue stiffness (PMID:25048396)
• Results show that LOXL2 is highly expressed and involved in clear cell renal cell carcinoma progression by regulating the levels of integrins a5 and b1. (PMID:25092917)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	loxl2b	ENSDARG00000044074
mus_musculus	Loxl2	ENSMUSG00000034205
rattus_norvegicus	Loxl2	ENSRNOG00000016758
drosophila_melanogaster	Loxl1	FBGN0039848

Paralogs (15): CD6 (ENSG00000013725), CD5L (ENSG00000073754), LGALS3BP (ENSG00000108679), CD5 (ENSG00000110448), LOX (ENSG00000113083), LOXL3 (ENSG00000115318), LOXL1 (ENSG00000129038), LOXL4 (ENSG00000138131), SSC4D (ENSG00000146700), PRSS12 (ENSG00000164099), CD163 (ENSG00000177575), CD163L1 (ENSG00000177675), SSC5D (ENSG00000179954), DMBT1 (ENSG00000187908), SCART1 (ENSG00000214279)

Protein

Protein identifiers

Lysyl oxidase homolog 2 — Q9Y4K0 (reviewed: Q9Y4K0)

Alternative names: Lysyl oxidase-like protein 2, Lysyl oxidase-related protein 2, Lysyl oxidase-related protein WS9-14

All UniProt accessions (9): E5RFE2, E5RFY0, E5RHH3, E5RI22, E5RJL2, Q9Y4K0, H0YAP6, H0YAR1, R4GMS2

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine). Acts as a transcription corepressor and specifically mediates deamination of trimethylated ‘Lys-4’ of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation. Shows no activity against histone H3 when it is trimethylated on ‘Lys-9’ (H3K9me3) or ‘Lys-27’ (H3K27me3) or when ‘Lys-4’ is monomethylated (H3K4me1) or dimethylated (H3K4me2). Also mediates deamination of methylated TAF10, a member of the transcription factor IID (TFIID) complex, which induces release of TAF10 from promoters, leading to inhibition of TFIID-dependent transcription. LOXL2-mediated deamination of TAF10 results in transcriptional repression of genes required for embryonic stem cell pluripotency including POU5F1/OCT4, NANOG, KLF4 and SOX2. Involved in epithelial to mesenchymal transition (EMT) via interaction with SNAI1 and participates in repression of E-cadherin CDH1, probably by mediating deamination of histone H3. During EMT, involved with SNAI1 in negatively regulating pericentromeric heterochromatin transcription. SNAI1 recruits LOXL2 to pericentromeric regions to oxidize histone H3 and repress transcription which leads to release of heterochromatin component CBX5/HP1A, enabling chromatin reorganization and acquisition of mesenchymal traits. Interacts with the endoplasmic reticulum protein HSPA5 which activates the IRE1-XBP1 pathway of the unfolded protein response, leading to expression of several transcription factors involved in EMT and subsequent EMT induction. Involved in E-cadherin repression following hypoxia, a hallmark of EMT believed to amplify tumor aggressiveness, suggesting that it may play a role in tumor progression. When secreted into the extracellular matrix, promotes cross-linking of extracellular matrix proteins by mediating oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin. Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding. Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation.

Subunit / interactions. Component of some chromatin repressor complex. Interacts with SNAI1. Interacts with TAF10. Interacts with HSPA5. Interacts with EFEMP2.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane. Nucleus. Chromosome. Endoplasmic reticulum.

Tissue specificity. Expressed in many tissues. Highest expression in reproductive tissues, placenta, uterus and prostate. In esophageal epithelium, expressed in the basal, prickle and granular cell layers. Up-regulated in a number of cancers cells and tissues.

Post-translational modifications. The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine. N-glycosylated. N-glycosylation on Asn-455 and Asn-644 may be essential for proper folding and secretion; may be composed of a fucosylated carbohydrates attached to a trimannose N-linked glycan core.

Activity regulation. According to some reports, it is inhibited by beta-aminopropionitrile (BAPN). According to another report, it is not inhibited by beta-aminopropionitrile (BAPN). Specifically inhibited by a mouse monoclonal antibody AB0023, inhibition occurs in a non-competitive manner.

Cofactor. Contains 1 lysine tyrosylquinone.

Domain organisation. The fourth SRCR domain plays an important role in optimizing the catalytic activity of the lysyl-oxidase like (LOX) catalytic domain.

Induction. Strongly induced in hypoxia. Direct transcriptional target of HIF1A.

Miscellaneous. Its overexpression in a number of cancers and its ability to promote epithelial to mesenchymal transition suggest that LOXL2 might play a role in tumor progression: expression is correlated with metastasis and decreased survival in patients with aggressive breast cancer. Allosteric inhibition by AB0023 inhibits formation of the tumor microenvironment and reduces metastatic tumor burden in xenograft models. However, inhibiting the enzyme activity of LOXL2 may not be sufficient, since inhibition of keratinocyte differentiation is not prevented in mutants that lack enzyme activity nor by inhibition of activity by the AB0023 antibody, thereby promoting development of squamous cell carcinomas.

Similarity. Belongs to the lysyl oxidase family.

RefSeq proteins (1): NP_002309* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001190	SRCR	Domain
IPR001695	Lysyl_oxidase	Family
IPR019828	Lysyl_oxidase_CS	Conserved_site
IPR036772	SRCR-like_dom_sf	Homologous_superfamily
IPR050912

Pfam: PF00530, PF01186

Enzyme classification (BRENDA):

• EC 1.4.3.13 — protein-lysine 6-oxidase (BRENDA: 17 organisms, 78 substrates, 106 inhibitors, 3 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1,5-DIAMINOPENTANE	0.373	1

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl-[protein] + O2 + H2O = (S)-2-amino-6-oxohexanoyl-[protein] + H2O2 + NH4(+) (RHEA:24544)

UniProt features (97 total): strand 28, disulfide bond 17, helix 10, binding site 9, mutagenesis site 9, sequence conflict 6, domain 4, turn 4, glycosylation site 3, sequence variant 2, signal peptide 1, chain 1, modified residue 1, cross-link 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5ZE3	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4K0-F1	85.92	0.63

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 (9): 628; 630; 722; 724; 727; 728; 549; 550; 626

Post-translational modifications (2): 689, 653–689

Disulfide bonds (17): 84–148, 97–158, 128–138, 218–291, 231–301, 265–275, 351–414, 364–424, 395–405, 464–530, 477–543, 511–521, 573–625, 579–695, 657–673, 663–685, 732–746

Glycosylation sites (3): 288, 455, 644

Mutagenesis-validated functional residues (9):

Position	Phenotype
455	inhibits secretion.
626–628	abolishes oxidase activity and oxidation of trimethylated ’lys-4’ of histone h3 but does not affect secretion, interacti
626	loss of enzyme activity.
628	loss of enzyme activity.
630	loss of enzyme activity.
644	inhibits secretion.
653	loss of enzyme activity.
689	loss of enzyme activity.
689	does not affect ability to inhibit keratinocyte differentiation.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1566948	Elastic fibre formation
R-HSA-2243919	Crosslinking of collagen fibrils
R-HSA-1474244	Extracellular matrix organization
R-HSA-1474290	Collagen formation
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures

MSigDB gene sets: 227 (showing top): MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, KENNY_CTNNB1_TARGETS_UP, GNF2_PTX3, GOBP_RESPONSE_TO_COPPER_ION, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, GOBP_RESPONSE_TO_METAL_ION, PATIL_LIVER_CANCER, MODULE_118

GO Biological Process (16): negative regulation of transcription by RNA polymerase II (GO:0000122), response to hypoxia (GO:0001666), epithelial to mesenchymal transition (GO:0001837), endothelial cell proliferation (GO:0001935), sprouting angiogenesis (GO:0002040), positive regulation of epithelial to mesenchymal transition (GO:0010718), peptidyl-lysine oxidation (GO:0018057), collagen fibril organization (GO:0030199), positive regulation of chondrocyte differentiation (GO:0032332), protein modification process (GO:0036211), endothelial cell migration (GO:0043542), negative regulation of DNA-templated transcription (GO:0045892), response to copper ion (GO:0046688), heterochromatin organization (GO:0070828), negative regulation of stem cell population maintenance (GO:1902455), chromatin organization (GO:0006325)

GO Molecular Function (8): protein-lysine 6-oxidase activity (GO:0004720), copper ion binding (GO:0005507), calcium ion binding (GO:0005509), oligosaccharide binding (GO:0070492), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor (GO:0016641), metal ion binding (GO:0046872)

GO Cellular Component (10): chromatin (GO:0000785), basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), extracellular matrix (GO:0031012), extracellular region (GO:0005576), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Extracellular matrix organization	2
Assembly of collagen fibrils and other multimeric structures	1
Collagen formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
positive regulation of cell differentiation	2
intracellular membrane-bounded organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
response to stress	1
response to decreased oxygen levels	1
mesenchymal cell differentiation	1
epithelial cell proliferation	1
angiogenesis	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of multicellular organismal process	1
protein oxidation	1
peptidyl-lysine modification	1
extracellular matrix organization	1
chondrocyte differentiation	1
regulation of chondrocyte differentiation	1
positive regulation of cartilage development	1
protein metabolic process	1
macromolecule modification	1
cell migration	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
response to metal ion	1
chromatin organization	1
stem cell population maintenance	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
regulation of stem cell population maintenance	1
cellular component organization	1
oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor	1
catalytic activity, acting on a protein	1
transition metal ion binding	1
metal ion binding	1
carbohydrate binding	1
binding	1
catalytic activity	1

Protein interactions and networks

STRING

1898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LOXL2	SNAI1	O95863	962
LOXL2	GATA6	P78327	908
LOXL2	ELN	P15502	818
LOXL2	FBLN5	Q9UBX5	770
LOXL2	BMP1	P13497	735
LOXL2	FN1	P02751	657
LOXL2	TGFB1	P01137	628
LOXL2	MMP2	P08253	582
LOXL2	PLOD2	O00469	581
LOXL2	HSPA5	P11021	524
LOXL2	MMP13	P45452	521
LOXL2	COL1A1	P02452	512
LOXL2	IGFBP5	P24593	497
LOXL2	IGFBP3	P17936	497
LOXL2	LCN2	P30150	492
LOXL2	POSTN	Q15063	492

IntAct

133 interactions, top by confidence:

A	B	Type	Score
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
CRIPTO	AIP	psi-mi:“MI:0914”(association)	0.640
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
TULP3	GGPS1	psi-mi:“MI:0914”(association)	0.640
LOXL2	VIM	psi-mi:“MI:0915”(physical association)	0.600
LOXL2	VIM	psi-mi:“MI:2364”(proximity)	0.600
VIM	LOXL2	psi-mi:“MI:2364”(proximity)	0.600
LOXL2	MARCKSL1	psi-mi:“MI:0915”(physical association)	0.580
LOXL2	ELN	psi-mi:“MI:0407”(direct interaction)	0.560
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
PSG8	PEX7	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
ADAMTS4	MANBA	psi-mi:“MI:0914”(association)	0.530
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
WNT7A	LDLR	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
INSL5	COCH	psi-mi:“MI:0914”(association)	0.530

BioGRID (450): LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), RBM14-RBM4 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS)

ESM2 similar proteins: A1L1V4, A6H737, B4F6N6, B5DF27, B8A4W9, E1C3U7, F1QQC3, F1RD85, M9PE65, O08762, O35548, O73798, O97827, P05156, P14210, P16264, P51512, P51559, P56730, P58022, P58215, P86091, Q08B63, Q17800, Q20911, Q5G265, Q5G266, Q5G267, Q5G268, Q5G269, Q5G270, Q5G271, Q5R5A4, Q5RDI1, Q5RFQ6, Q5W7F4, Q61129, Q7RTY8, Q7TQN3, Q80TS3

Diamond homologs: A1L0T3, A1L1V4, A1L4H1, A5PJQ2, A6H737, A7E3W2, B4F6N6, B5DF27, B8A4W9, E1C3U7, F1QQC3, F1RD85, F7J220, G3V801, M9NDE3, O08762, O43866, O70513, P21757, P21758, P30203, P30204, P30205, P56730, P58022, P58215, P70117, P85521, Q05585, Q07797, Q08380, Q08B63, Q14DK5, Q24JV9, Q2VL90, Q2VLG4, Q2VLG6, Q2VLH6, Q4A3R3, Q4G0T1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FOXA1	“up-regulates quantity by expression”	LOXL2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 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
Retinoid metabolism and transport	6	16.0×	5e-04
Hedgehog ‘off’ state	5	9.6×	9e-03
Post-translational modification: synthesis of GPI-anchored proteins	5	9.0×	9e-03
Degradation of the extracellular matrix	7	8.9×	2e-03
Extracellular matrix organization	10	6.8×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	150
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3123 predictions. Top by Δscore:

Variant	Effect	Δscore
8:23298830:CCTTA:C	donor_loss	1.0000
8:23298831:CTTA:C	donor_loss	1.0000
8:23298832:TTA:T	donor_loss	1.0000
8:23298833:TA:T	donor_loss	1.0000
8:23298834:A:AC	donor_gain	1.0000
8:23298835:C:CC	donor_gain	1.0000
8:23298944:CAAC:C	acceptor_gain	1.0000
8:23302022:CTCAC:C	donor_loss	1.0000
8:23302025:AC:A	donor_loss	1.0000
8:23302159:GATGT:G	acceptor_gain	1.0000
8:23302160:ATGT:A	acceptor_gain	1.0000
8:23302161:TGT:T	acceptor_gain	1.0000
8:23302162:GT:G	acceptor_gain	1.0000
8:23302164:C:A	acceptor_loss	1.0000
8:23302164:C:CC	acceptor_gain	1.0000
8:23302165:T:C	acceptor_loss	1.0000
8:23302171:C:CT	acceptor_gain	1.0000
8:23302172:A:T	acceptor_gain	1.0000
8:23303279:TAC:T	donor_loss	1.0000
8:23303280:ACCT:A	donor_gain	1.0000
8:23303281:C:CA	donor_loss	1.0000
8:23303281:CCTC:C	donor_gain	1.0000
8:23303283:T:TA	donor_gain	1.0000
8:23303284:C:A	donor_gain	1.0000
8:23309662:GCCTA:G	donor_loss	1.0000
8:23309663:CCTA:C	donor_loss	1.0000
8:23309664:CTAC:C	donor_loss	1.0000
8:23309665:TACCT:T	donor_loss	1.0000
8:23309909:CGG:C	acceptor_gain	1.0000
8:23316947:A:AC	donor_gain	1.0000

AlphaMissense

5138 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:23298887:A:G	C732R	1.000
8:23302069:C:A	W697C	1.000
8:23302069:C:G	W697C	1.000
8:23302071:A:G	W697R	1.000
8:23302071:A:T	W697R	1.000
8:23302075:G:C	C695W	1.000
8:23302076:C:T	C695Y	1.000
8:23302077:A:G	C695R	1.000
8:23303307:G:C	C657W	1.000
8:23303308:C:T	C657Y	1.000
8:23303309:A:G	C657R	1.000
8:23309688:C:A	W620C	1.000
8:23309688:C:G	W620C	1.000
8:23309761:A:G	L596P	1.000
8:23319951:C:A	W468C	1.000
8:23319951:C:G	W468C	1.000
8:23328467:C:A	W355C	1.000
8:23328467:C:G	W355C	1.000
8:23328469:A:G	W355R	1.000
8:23328469:A:T	W355R	1.000
8:23328491:C:A	W347C	1.000
8:23328491:C:G	W347C	1.000
8:23328493:A:G	W347R	1.000
8:23328493:A:T	W347R	1.000
8:23360178:C:G	C148S	1.000
8:23360179:A:T	C148S	1.000
8:23368100:G:C	C84W	1.000
8:23368101:C:T	C84Y	1.000
8:23298843:G:C	C746W	0.999
8:23298845:A:G	C746R	0.999

dbSNP variants (sampled 300 via entrez): RS1000009643 (8:23336503 G>A), RS1000017326 (8:23385863 C>T), RS1000035305 (8:23360027 A>C,G), RS1000067007 (8:23373052 A>C), RS1000069650 (8:23342664 C>T), RS1000100330 (8:23342791 C>T), RS1000149024 (8:23330099 G>A,C), RS1000155802 (8:23401009 CAAG>C), RS1000182454 (8:23327349 G>C), RS1000199393 (8:23304408 G>A), RS1000202591 (8:23380155 G>T), RS1000214257 (8:23362413 T>C), RS1000228321 (8:23335855 CT>C), RS1000249136 (8:23370040 G>C), RS1000258649 (8:23300635 T>C)

Disease associations

OMIM: gene MIM:606663 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000751_1	Attention deficit hyperactivity disorder	3.000000e-06
GCST005667_38	Central corneal thickness	2.000000e-08
GCST005957_7	Waist-to-hip ratio adjusted for BMI (age <50)	3.000000e-06
GCST005958_10	Waist-to-hip ratio adjusted for BMI (age >50)	3.000000e-08
GCST005962_21	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-11
GCST008839_228	Height	1.000000e-24
GCST012490_265	Femur bone mineral density x serum urate levels interaction	1.000000e-08
GCST90000025_324	Appendicular lean mass	1.000000e-16
GCST90000027_11	Appendicular lean mass	1.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005213	central corneal thickness
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3714029 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 133,533 (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
CHEMBL1356238	PYRITHIONE	4	15,582
CHEMBL964	DISULFIRAM	4	38,611
CHEMBL120563	THIRAM	2	79,340

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 1.4.3.13 Lysyl oxidases

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
simtuzumab	Inhibition	7.17	pKi
compound 21b [PMID: 31430136]	Inhibition	6.82	pIC50
CCT365623	Inhibition	5.82	pIC50

ChEMBL bioactivities

640 potent at pChembl≥5 of 667 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	IC50	3.981	nM	CHEMBL4457578
8.30	IC50	5.012	nM	CHEMBL4448713
8.30	IC50	5	nM	CHEMBL4457578
8.05	IC50	9	nM	CHEMBL4457578
7.90	IC50	12.59	nM	CHEMBL4556859
7.89	IC50	13	nM	CHEMBL4457578
7.70	IC50	19.95	nM	CHEMBL4531065
7.70	IC50	19.95	nM	CHEMBL4467234
7.70	IC50	19.95	nM	CHEMBL4458907
7.70	IC50	19.95	nM	CHEMBL4581458
7.60	IC50	25.12	nM	CHEMBL4582216
7.55	IC50	28	nM	CHEMBL4456063
7.55	IC50	28	nM	CHEMBL4515085
7.47	IC50	34	nM	CHEMBL4068580
7.46	IC50	35	nM	CHEMBL4084982
7.38	IC50	42	nM	CHEMBL4059919
7.37	IC50	43	nM	CHEMBL4082808
7.35	IC50	45	nM	CHEMBL4453775
7.35	IC50	45	nM	CHEMBL4597759
7.30	IC50	50	nM	CHEMBL4086010
7.30	IC50	50.12	nM	CHEMBL4569453
7.30	IC50	50.12	nM	CHEMBL4550754
7.28	IC50	53	nM	CHEMBL4103928
7.25	IC50	56	nM	CHEMBL4088453
7.25	IC50	56	nM	CHEMBL4526964
7.25	IC50	56	nM	CHEMBL4522781
7.25	IC50	56	nM	CHEMBL4594701
7.24	IC50	58	nM	CHEMBL4097435
7.24	IC50	58	nM	CHEMBL4551841
7.24	IC50	58	nM	CHEMBL4450748
7.22	IC50	60	nM	CHEMBL4540610
7.22	IC50	60	nM	CHEMBL4447452
7.21	IC50	62	nM	CHEMBL4067192
7.21	IC50	62	nM	CHEMBL4059919
7.21	IC50	62	nM	CHEMBL4084982
7.20	IC50	63.1	nM	CHEMBL4574820
7.19	IC50	64	nM	CHEMBL4518059
7.19	IC50	65	nM	CHEMBL4436117
7.19	IC50	65	nM	CHEMBL4564074
7.19	IC50	64	nM	CHEMBL4595733
7.18	IC50	66	nM	CHEMBL1618272
7.18	IC50	66	nM	CHEMBL4439162
7.18	IC50	66	nM	CHEMBL4598011
7.17	IC50	67	nM	CHEMBL4089707
7.17	IC50	68	nM	CHEMBL4467908
7.17	IC50	68	nM	CHEMBL4596100
7.16	IC50	69	nM	CHEMBL4568508
7.16	IC50	69	nM	CHEMBL4457897
7.16	IC50	70	nM	CHEMBL4573381
7.16	IC50	70	nM	CHEMBL4461466

PubChem BioAssay actives

214 with measured affinity, of 308 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
1-[(Z)-4-amino-2-fluorobut-2-enyl]-3-[3-(dimethylsulfamoyl)phenyl]-2-methylindole-5-carboxylic acid;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.0040	uM
3-[1-[(Z)-4-amino-2-fluorobut-2-enyl]-2-methyl-5-methylsulfonylindol-3-yl]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.0050	uM
4-[[1-[(Z)-4-amino-2-fluorobut-2-enyl]triazol-4-yl]methyl]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.0126	uM
3-[1-[(Z)-4-amino-2-fluorobut-2-enyl]-5-(methanesulfonamido)-2-methylindol-3-yl]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.0199	uM
3-[1-[(Z)-4-amino-2-fluorobut-2-enyl]-2-methylpyrrolo[3,2-b]pyridin-3-yl]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.0199	uM
4-[[1-[(Z)-4-amino-2-fluorobut-2-enyl]triazol-4-yl]methylamino]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.0199	uM
4-[[1-[(Z)-4-amino-2-fluorobut-2-enyl]triazol-4-yl]methoxy]-3-chloro-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.0199	uM
1-[(Z)-4-amino-2-fluorobut-2-enyl]-3-[3-(dimethylsulfamoyl)phenyl]-N,N,2-trimethylindole-5-carboxamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.0251	uM
3-[[4-(aminomethyl)-6-(trifluoromethyl)-2-pyridinyl]oxy]-N-(1-benzothiophen-2-ylmethyl)benzamide;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0340	uM
3-[[4-(aminomethyl)-6-(trifluoromethyl)-2-pyridinyl]oxy]-N-(2-sulfamoylethyl)benzamide;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0350	uM
3-[[4-(aminomethyl)-6-(trifluoromethyl)-2-pyridinyl]oxy]-N-phenylbenzamide;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0420	uM
3-[[4-(aminomethyl)-6-(trifluoromethyl)-2-pyridinyl]oxy]-N-[2-(tetrazol-1-yl)ethyl]benzamide;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0430	uM
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-(4-fluorophenyl)benzamide;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0500	uM
3-[1-[(Z)-4-amino-2-fluorobut-2-enyl]-5-hydroxy-2-methylindol-3-yl]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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
4-[[1-[(Z)-4-amino-2-fluorobut-2-enyl]triazol-4-yl]methoxy]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-(4-methoxyphenyl)benzamide;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0530	uM
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-phenylbenzamide;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0560	uM
[3-[[4-(aminomethyl)-6-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]-[(3R)-3-aminopyrrolidin-1-yl]methanone;dihydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0580	uM
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-benzylbenzamide;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0620	uM
1-[(Z)-4-amino-2-fluorobut-2-enyl]-3-[3-(dimethylsulfamoyl)phenyl]-N,N,2-trimethylindole-6-carboxamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.0631	uM
3-aminopropanenitrile	1430567: Inhibition of full length recombinant human LOXL2 expressed in CHO cells assessed as reduction in H2O2 production using DAP as substrate preincubated for 2 hrs followed by substrate addition measured every 2 minutes for 50 minutes by Amplex red dye based fluorescence assay	ic50	0.0660	uM
[2-(3-phenoxyphenoxy)-6-(trifluoromethyl)-4-pyridinyl]methanamine	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0670	uM
[5-(3-methylsulfonyl-5-phenylphenyl)sulfonyl-1,3-thiazol-2-yl]methanamine	1604044: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 3 hrs followed by substrate addition by ROS-Glo assay	ic50	0.0690	uM
[5-[3-(1-methylpyrazol-4-yl)-5-methylsulfonylphenyl]sulfonyl-1,3-thiazol-2-yl]methanamine	1604044: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 3 hrs followed by substrate addition by ROS-Glo assay	ic50	0.0690	uM
[3-[[4-(aminomethyl)-2-pyridinyl]oxy]phenyl]-[(3R,4R)-3-fluoro-4-hydroxypyrrolidin-1-yl]methanone;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0740	uM
3-[[4-(aminomethyl)-6-(trifluoromethyl)-2-pyridinyl]oxy]-N-[(2R)-2,3-dihydroxypropyl]benzamide;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0770	uM
[5-[3-ethyl-5-(1-methylpyrazol-4-yl)phenyl]sulfonyl-1,3-thiazol-2-yl]methanamine	1604044: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 3 hrs followed by substrate addition by ROS-Glo assay	ic50	0.0780	uM
[3-[[4-(aminomethyl)-6-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]-[(3R,4R)-3-fluoro-4-hydroxypyrrolidin-1-yl]methanone;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0780	uM
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-(1-benzothiophen-2-ylmethyl)benzamide;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0790	uM
3-[1-[(Z)-4-amino-2-fluorobut-2-enyl]-5-methoxy-2-methylindol-3-yl]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.0794	uM
ethyl 1-[(Z)-4-amino-2-fluorobut-2-enyl]-3-[3-(dimethylsulfamoyl)phenyl]-2-methylindole-5-carboxylate;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.0794	uM
4-[[3-[[4-(aminomethyl)-2-pyridinyl]oxy]benzoyl]amino]benzoic acid;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0810	uM
[3-[[4-(aminomethyl)-2-pyridinyl]oxy]phenyl]-[(3S,4S)-3-fluoro-4-hydroxypyrrolidin-1-yl]methanone;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0820	uM
[4-(3-methylsulfonyl-5-phenylphenyl)sulfonyl-1,3-thiazol-2-yl]methanamine	1604044: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 3 hrs followed by substrate addition by ROS-Glo assay	ic50	0.0850	uM
3-[[4-(aminomethyl)-6-(trifluoromethyl)-2-pyridinyl]oxy]-N-methoxybenzamide;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.0960	uM
3-[1-[(Z)-4-amino-2-fluorobut-2-enyl]-2-methylindol-3-yl]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.1000	uM
3-[1-[(Z)-4-amino-2-fluorobut-2-enyl]pyrrol-3-yl]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.1000	uM
[5-[3-(4-methylphenyl)-5-methylsulfonylphenyl]sulfonyl-1,3-thiazol-2-yl]methanamine	1604043: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 1 hr followed by substrate addition by ROS-Glo assay	ic50	0.1030	uM
[3-[[4-(aminomethyl)-6-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]-[(3R)-3-hydroxypyrrolidin-1-yl]methanone;hydrochloride	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.1100	uM
[3-[[4-(aminomethyl)-2-pyridinyl]oxy]phenyl]-(3,4-dihydro-1H-isoquinolin-2-yl)methanone	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.1200	uM
(5-naphthalen-2-ylsulfonyl-1,3-thiazol-2-yl)methanamine	1604044: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 3 hrs followed by substrate addition by ROS-Glo assay	ic50	0.1200	uM
3-[1-[(Z)-4-amino-2-fluorobut-2-enyl]-2-methyl-5-(2H-tetrazol-5-yl)indol-3-yl]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.1259	uM
3-[1-[(Z)-4-amino-2-fluorobut-2-enyl]-5-chloro-2-methylindol-3-yl]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.1259	uM
4-[1-[(Z)-4-amino-2-fluorobut-2-enyl]triazol-4-yl]-N,N-dimethylbenzenesulfonamide;hydrochloride	1526666: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine 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	0.1259	uM
[5-(3-methylsulfonyl-5-phenylphenyl)sulfonylthiophen-2-yl]methanamine	1604044: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 3 hrs followed by substrate addition by ROS-Glo assay	ic50	0.1260	uM
(2-chloro-4-pyridinyl)methanamine	1430567: Inhibition of full length recombinant human LOXL2 expressed in CHO cells assessed as reduction in H2O2 production using DAP as substrate preincubated for 2 hrs followed by substrate addition measured every 2 minutes for 50 minutes by Amplex red dye based fluorescence assay	ic50	0.1260	uM
(3S)-3-[[4-(aminomethyl)-6-(trifluoromethyl)-2-pyridinyl]oxy]-N-phenylpiperidine-1-carboxamide	1483214: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	0.1300	uM
[5-[3-fluoro-5-(1-methylpyrazol-4-yl)phenyl]sulfonyl-1,3-thiazol-2-yl]methanamine	1604043: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 1 hr followed by substrate addition by ROS-Glo assay	ic50	0.1430	uM
[4-[3-(1-methylpyrazol-4-yl)-5-methylsulfonylphenyl]sulfonyl-1,3-thiazol-2-yl]methanamine	1604044: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 3 hrs followed by substrate addition by ROS-Glo assay	ic50	0.1460	uM
Disulfiram	1399350: Inhibition of recombinant LOXL2 (unknown origin) expressed in NS0 cells using diaminopentane as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorimetric method	ic50	0.1500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression, decreases methylation, increases expression	4
Valproic Acid	affects expression, increases expression	4
Cadmium Chloride	increases abundance, increases expression, decreases expression	4
Air Pollutants	increases expression, affects methylation, increases abundance, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Tetrachlorodibenzodioxin	increases expression	3
graphene oxide	increases expression	2
sodium arsenite	decreases expression, affects methylation	2
cobaltous chloride	increases expression	2
Particulate Matter	increases abundance, affects expression, increases reaction, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
tungsten carbide	increases expression, affects binding	1
testosterone enanthate	affects expression	1
titanium dioxide	decreases methylation	1
trichostatin A	increases expression, increases reaction	1
beta-lapachone	increases expression	1
benzo(e)pyrene	increases methylation	1
cupric chloride	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
bisphenol B	increases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
jinfukang	increases expression	1
NSC 689534	increases expression	1
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression	1
GSK1210151A	decreases reaction, increases expression, decreases expression	1
2-methoxy-N-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzenesulfonamide	decreases reaction, increases expression, decreases expression	1
bisphenol AF	increases expression	1

ChEMBL screening assays

63 unique, capped per target: 62 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3997540	Binding	Inhibition of full length recombinant human LOXL2 expressed in CHO cells assessed as reduction in H2O2 production using DAP as substrate preincubated for 15 mins followed by substrate addition measured every 2 minutes for 50 minutes by Ampl	Small Molecule Lysyl Oxidase-like 2 (LOXL2) Inhibitors: The Identification of an Inhibitor Selective for LOXL2 over LOX. — ACS Med Chem Lett
CHEMBL4323305	ADMET	Substrate activity at recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells assessed as oxidative turnover at 30 uM measured after 30 mins by horseradish peroxidase-coupled amplex red reagent-based	Identification and Optimization of Mechanism-Based Fluoroallylamine Inhibitors of Lysyl Oxidase-like 2/3. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1W1	Abcam HeLa LOXL2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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