LOX

Summary

LOX (lysyl oxidase, HGNC:6664) is a protein-coding gene on chromosome 5q23.1, encoding Protein-lysine 6-oxidase (P28300). Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin.

This gene encodes a member of the lysyl oxidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a regulatory propeptide and the mature enzyme. The copper-dependent amine oxidase activity of this enzyme functions in the crosslinking of collagens and elastin, while the propeptide may play a role in tumor suppression. In addition, defects in this gene have been linked with predisposition to thoracic aortic aneurysms and dissections.

Source: NCBI Gene 4015 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial thoracic aortic aneurysm and aortic dissection (Strong, ClinGen) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 636 total — 28 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 60
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6664
Approved symbol	LOX
Name	lysyl oxidase
Location	5q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113083
Ensembl biotype	protein_coding
OMIM	153455
Entrez	4015

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000231004, ENST00000503759, ENST00000505593, ENST00000508067, ENST00000513319, ENST00000639739, ENST00000939087

RefSeq mRNA: 3 — MANE Select: NM_002317 NM_001178102, NM_001317073, NM_002317

CCDS: CCDS4129, CCDS93766, CCDS93767

Canonical transcript exons

ENST00000231004 — 7 exons

Exon	Start	End
ENSE00000761235	122076893	122077001
ENSE00001082205	122063195	122066749
ENSE00001891683	122077355	122078259
ENSE00003492280	122075404	122075541
ENSE00003595228	122074013	122074169
ENSE00003647722	122070053	122070168
ENSE00003693101	122070494	122070589

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 166.3436 / max 8243.8082, expressed in 1223 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63126	104.4508	1069
63128	19.3987	941
63129	16.9957	1026
63127	14.2752	914
63124	5.3648	560
63122	1.8261	650
63125	1.6391	431
63123	1.0001	551
63120	0.8832	311
63130	0.3257	161

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.52	gold quality
calcaneal tendon	UBERON:0003701	97.94	gold quality
tibia	UBERON:0000979	97.62	gold quality
skin of hip	UBERON:0001554	97.50	gold quality
periodontal ligament	UBERON:0008266	95.82	gold quality
cartilage tissue	UBERON:0002418	95.40	gold quality
pericardium	UBERON:0002407	94.53	gold quality
ventricular zone	UBERON:0003053	94.03	gold quality
upper arm skin	UBERON:0004263	93.78	gold quality
upper leg skin	UBERON:0004262	93.49	gold quality
parietal pleura	UBERON:0002400	92.99	gold quality
right lung	UBERON:0002167	92.65	gold quality
pleura	UBERON:0000977	92.60	gold quality
visceral pleura	UBERON:0002401	92.07	gold quality
tendon	UBERON:0000043	91.96	gold quality
metanephric glomerulus	UBERON:0004736	91.19	gold quality
renal glomerulus	UBERON:0000074	91.06	gold quality
gall bladder	UBERON:0002110	91.05	gold quality
saphenous vein	UBERON:0007318	90.85	gold quality
ascending aorta	UBERON:0001496	90.67	gold quality
thoracic aorta	UBERON:0001515	90.56	gold quality
adipose tissue	UBERON:0001013	90.53	gold quality
descending thoracic aorta	UBERON:0002345	90.50	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.38	gold quality
connective tissue	UBERON:0002384	90.37	gold quality
aorta	UBERON:0000947	89.85	gold quality
tibial artery	UBERON:0007610	89.46	gold quality
popliteal artery	UBERON:0002250	89.42	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.37	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.66	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	1623.75
E-MTAB-8205	yes	173.73
E-CURD-112	yes	18.04
E-MTAB-7052	no	2210.33
E-MTAB-10290	no	628.36
E-MTAB-6678	no	594.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPG, DNMT1, FLI1, GATA3, HIF1A, HIF3A, HMGA2, MYBL2, NFKB, TP53

miRNA regulators (miRDB)

203 targeting LOX, 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-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996

Literature-anchored findings (GeneRIF, showing 40)

• Polymorphisms of the LOX gene were genotyped in 192 ALS patients, including 31 unrelated familial cases and 138 controls, and no association was found between any of these polymorphisms and amyotrophic lateral sclerosis or its phenotype. (PMID:11675877)
• Loss or reduction of LOX function during tumor development is a direct consequence of somatic mutations and associated with colon tumor pathogenesis. (PMID:11807790)
• lysyl oxidase gene may play an important role in metastasis of esophageal, cardiac, and gastric carcinomas (PMID:12452073)
• comparison and aa sequence alignment of human and rat lysyl oxidase and lysyl oxidase-like gene (LOXL1); role in formation and repair of ECM elastin and collagen (PMID:12577300)
• Lysyl oxidase(LOX) could actually interact specifically not only with histone H1, but also with histone H2. (PMID:12686141)
• No associations of intracranial aneurysm and LOX were found. (PMID:12750963)
• LOX-mRNA level in both cell lines and tissues of HNSCC was markedly reduced as opposed to benign keratinocyte cell lines and mucosal tissue samples of the upper aerodigestive tract suggesting that LOX is involved in tumor suppressive processes. (PMID:12820424)
• LOX regulates control of normal collagen deposition in differentiating osteoblast cultures. (PMID:15137057)
• Four genetic variants including 2 novel polymorphisms, 1 in the noncoding sequence of exon 7 and the other upstream from lysyl oxidase promoter. None showed allelic association or cosegregation with intracranial aneurysm in families. (PMID:15273433)
• LOX is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in gastric cancers, and possibly also in other cancers. (PMID:15374948)
• the FN matrix may provide specific microenvironments to regulate LOX catalytic activity (PMID:15843371)
• Upregulation of Lox 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)
• pro-regions of lysyl oxidase and lysyl oxidase-like 1 are required for deposition onto elastic fibers (PMID:16251195)
• up-regulation of lysyl oxidase is associated with invasive breast cancer through a hydrogen peroxide-mediated mechanism involving the FAK/Src signaling pathway (PMID:16357151)
• LOX regulates cell motility/migration through changes in actin filament polymerization, which involve the regulation of the p130(Cas)/Crk/DOCK180 (PMID:16440329)
• Absence of lysyl oxidase is associated with basal and squamous cell carcinomas of the skin (PMID:16533769)
• LOX regulates the promoter of elastin, inducing an important activation of its activity. (PMID:17395448)
• BCL2 repression by the tumor suppressor activity of the lysyl oxidase propeptide inhibits transformed phenotype of lung and pancreatic cancer cells (PMID:17616686)
• By using both TNF receptor (TNFR) agonist and blocking antibodies we determined the involvement of TNFR2 on LOX down-regulation (PMID:17673218)
• LOX participates, in part, in the remodeling of the heart leading to cardiac dysfunction and heart failure. (PMID:17849172)
• LOX activity showed a statistically significant decrease in the vitreous of PDR and RRD relative to control specimens. This effect can contribute to the inadequate collagen cross-linking that causes the ECM changes that occur in these diseases. (PMID:18566459)
• There was a borderline of statistically significant difference in Arg158Gln genotype lying between control and OSF patients. G/A+A/A of LOX Arg158Gln in OSF patients older than 50 was statistically significantly higher than controls older than 50. (PMID:18764858)
• lysyl oxidase and glucose transporter-1 expression have roles in prostate cancer progression (PMID:19020742)
• The lysyl oxidase pro-peptide attenuates fibronectin-mediated activation of focal adhesion kinase and p130Cas in breast cancer cells. (PMID:19029090)
• The results suggest that decreased expression of elastin and LOX and increased expression of elafin in the cardinal ligaments may contribute to pelvic organ prolapse. (PMID:19087518)
• demonstrate a critical role for LOX in premetastatic niche formation and support targeting LOX for the treatment and prevention of metastatic disease (PMID:19111879)
• Report reciprocal regulation of LOX and LOXL2 expression during cell adhesion and terminal differentiation in epidermal keratinocytes. (PMID:19394199)
• Statins normalize vascular lysyl oxidase down-regulation induced by proatherogenic risk factors. (PMID:19406911)
• High Lysyl oxidase is associated with lymph node metastasis in esophageal squamous cell carcinoma. (PMID:19526206)
• LOX protein is overexpressed in polycystic ovarian tissue, and transcriptional activity of the LOX promoter is regulated by AGE signalling. (PMID:19583806)
• Genetic polymorphism as a mechanism of impaired tumor suppressor function of LOX-propeptide and it may play an etiologic role in ER-negative breast cancer. (PMID:19654310)
• a causal relationship between mtDNA deletions, reactive oxygen species production, and increased LOX activity that leads to increased contraction of collagen gels (PMID:19661442)
• Study validates that LOX is a marker for metastasis and survival in HNC. (PMID:19667273)
• LOX upregulation may be associated with increased invasiveness and metastatic potential in colorectal cancer. (PMID:19724858)
• Lysyl oxidase overexpression may be an early phenomenon in the pathogenesis of oropharyngeal squamous cell carcinoma and thus a noven target for chemopreventive and therapeutic strategies. (PMID:19816945)
• 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)
• Methylation in the promoter region may suppress LOX gene expression in women with pelvic organ prolapse (PMID:20146053)
• Our study is the first to show lysyl oxidase expression in primary choroidal melanomas. (PMID:20179655)
• The loss of Pdcd4 early in cancer progression may have an important role in the increased sensitivity of cancer cells to hypoxia through increased LOX activity and concomitant enhanced invasiveness. (PMID:20498644)
• requirement of the LOX-PrePeptide for pro-LOX exit from the ER and the influence of LOX-PP glycosylation on LOX enzyme activity. (PMID:20717923)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	loxa	ENSDARG00000003259
mus_musculus	Lox	ENSMUSG00000024529
rattus_norvegicus	Lox	ENSRNOG00000014426

Paralogs (15): CD6 (ENSG00000013725), CD5L (ENSG00000073754), LGALS3BP (ENSG00000108679), CD5 (ENSG00000110448), LOXL3 (ENSG00000115318), LOXL1 (ENSG00000129038), LOXL2 (ENSG00000134013), LOXL4 (ENSG00000138131), SSC4D (ENSG00000146700), PRSS12 (ENSG00000164099), CD163 (ENSG00000177575), CD163L1 (ENSG00000177675), SSC5D (ENSG00000179954), DMBT1 (ENSG00000187908), SCART1 (ENSG00000214279)

Protein

Protein identifiers

Protein-lysine 6-oxidase — P28300 (reviewed: P28300)

Alternative names: Lysyl oxidase

All UniProt accessions (6): P28300, A0A7P0SNB0, B0AZT2, B7ZAJ4, D0PNI2, H0YAL3

UniProt curated annotations — full annotation on UniProt →

Function. Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin. Regulator of Ras expression. May play a role in tumor suppression. Plays a role in the aortic wall architecture.

Subunit / interactions. Interacts with MFAP4. Interacts (via propeptide) with EFEMP2; this interaction is strong and facilitates formation of ternary complexes with ELN during elastic fiber assembly; this interaction limits interaction of EFEMP2 with FBLN5.

Subcellular location. Secreted. Extracellular space.

Tissue specificity. Heart, placenta, skeletal muscle, kidney, lung and pancreas.

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. Proteolytically cleaved by BMP1 which removes the propeptide. Also proteolytically cleaved by ADAMTS2 and ADAMTS14, but not by ADAMTS3, at an additional cleavage site downstream of the BMP1 cleavage site. The propeptide plays a role in directing the deposition of this enzyme to elastic fibers, via interaction with tropoelastin. Cleavage by BMP1 to remove the propeptide does not increase enzymatic activity but increases binding to collagen. Cleavage by ADAMTS2 produces a form with reduced collagen-binding activity. Sulfated at Tyr-187 and also at either Tyr-183 or Tyr-184 which enhances binding to collagen.

Disease relevance. Aortic aneurysm, familial thoracic 10 (AAT10) [MIM:617168] A form of thoracic aortic aneurysm, a disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as ‘medial necrosis’ or ‘Erdheim cystic medial necrosis’ in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Contains 1 lysine tyrosylquinone.

Similarity. Belongs to the lysyl oxidase family.

RefSeq proteins (3): NP_001171573, NP_001304002, NP_002308* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001695	Lysyl_oxidase	Family
IPR019828	Lysyl_oxidase_CS	Conserved_site
IPR050912

Pfam: 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 (42 total): sequence variant 8, sequence conflict 8, disulfide bond 5, binding site 3, glycosylation site 3, mutagenesis site 3, region of interest 3, modified residue 2, chain 2, signal peptide 1, propeptide 1, site 1, cross-link 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28300-F1	68.06	0.35

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 (1): 218–219 (cleavage; by adamts2 and adamts14)

Ligand- & substrate-binding residues (3): 296; 292; 294

Post-translational modifications (3): 187, 355, 320–355

Disulfide bonds (5): 238–244, 291–340, 324–330, 351–361, 398–412

Glycosylation sites (3): 81, 97, 144

Mutagenesis-validated functional residues (3):

Position	Phenotype
183–184	abolishes sulfation and reduces binding to collagen; when associated with 186-f-f-187 and f-190.
186–187	abolishes sulfation and reduces binding to collagen; when associated with 183-f-f-184 and f-190.
190	abolishes sulfation and reduces binding to collagen; when associated with 183-f-f-184 and 186-f-f-187.

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: 502 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, MODULE_52, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_CELL_CHEMOTAXIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_RESPONSE_TO_PEPTIDE, GOCC_COLLAGEN_TRIMER, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MENSE_HYPOXIA_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_OSTEOBLAST_DIFFERENTIATION

GO Biological Process (31): osteoblast differentiation (GO:0001649), heart development (GO:0007507), response to xenobiotic stimulus (GO:0009410), regulation of gene expression (GO:0010468), regulation of striated muscle tissue development (GO:0016202), regulation of transforming growth factor beta receptor signaling pathway (GO:0017015), peptidyl-lysine oxidation (GO:0018057), collagen fibril organization (GO:0030199), bone mineralization (GO:0030282), lung development (GO:0030324), platelet-derived growth factor receptor-beta signaling pathway (GO:0035791), ascending aorta development (GO:0035905), descending aorta development (GO:0035906), protein modification process (GO:0036211), regulation of apoptotic process (GO:0042981), regulation of megakaryocyte differentiation (GO:0045652), muscle cell cellular homeostasis (GO:0046716), elastic fiber assembly (GO:0048251), blood vessel morphogenesis (GO:0048514), response to steroid hormone (GO:0048545), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), muscle cell development (GO:0055001), cell chemotaxis (GO:0060326), connective tissue development (GO:0061448), DNA biosynthetic process (GO:0071897), regulation of bone development (GO:1903010), cellular response to chemokine (GO:1990869), regulation of platelet-derived growth factor receptor-beta signaling pathway (GO:2000586), blood vessel development (GO:0001568), response to hormone (GO:0009725), aorta development (GO:0035904)

GO Molecular Function (9): protein-lysine 6-oxidase activity (GO:0004720), copper ion binding (GO:0005507), collagen binding (GO:0005518), small molecule binding (GO:0036094), molecular adaptor activity (GO:0060090), 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 (4): extracellular region (GO:0005576), collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012)

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
binding	3
ossification	2
animal organ development	2
aorta development	2
anatomical structure development	2
cell differentiation	1
circulatory system development	1
response to chemical	1
gene expression	1
regulation of macromolecule biosynthetic process	1
striated muscle tissue development	1
regulation of muscle organ development	1
regulation of muscle tissue development	1
transforming growth factor beta receptor signaling pathway	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of cellular response to transforming growth factor beta stimulus	1
protein oxidation	1
peptidyl-lysine modification	1
extracellular matrix organization	1
biomineral tissue development	1
respiratory tube development	1
respiratory system development	1
platelet-derived growth factor receptor signaling pathway	1
protein metabolic process	1
macromolecule modification	1
apoptotic process	1
regulation of programmed cell death	1
megakaryocyte differentiation	1
regulation of myeloid cell differentiation	1
cellular homeostasis	1
extracellular matrix assembly	1
supramolecular fiber organization	1
blood vessel development	1
tube morphogenesis	1
response to hormone	1
response to lipid	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
protein-containing complex binding	1

Protein interactions and networks

STRING

5340 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LOX	ELN	P15502	952
LOX	FBLN5	Q9UBX5	900
LOX	ALOX15	P16050	852
LOX	EFEMP2	O95967	847
LOX	ALOX15B	O15296	817
LOX	ALOXE3	Q9BYJ1	803
LOX	FN1	P02751	799
LOX	ALOX5	P09917	776
LOX	THBS1	P07996	774
LOX	ALOX12B	O75342	773
LOX	MFAP2	P55001	769
LOX	PTGS2	P35354	760
LOX	PLOD1	Q02809	756
LOX	POSTN	Q15063	753
LOX	OLR1	P78380	746

IntAct

85 interactions, top by confidence:

A	B	Type	Score
EFEMP2	LOX	psi-mi:“MI:0915”(physical association)	0.730
EFEMP2	LOX	psi-mi:“MI:0407”(direct interaction)	0.730
LOX	EFEMP2	psi-mi:“MI:0407”(direct interaction)	0.730
LOX	EFEMP2	psi-mi:“MI:0915”(physical association)	0.730
ELN	EFEMP2	psi-mi:“MI:0915”(physical association)	0.650
FBLN5	EFEMP2	psi-mi:“MI:0915”(physical association)	0.610
LOX	PTPRK	psi-mi:“MI:0915”(physical association)	0.580
PTPRK	LOX	psi-mi:“MI:0915”(physical association)	0.580
FBLN5	LOX	psi-mi:“MI:0915”(physical association)	0.570
LOX	FBN1	psi-mi:“MI:0407”(direct interaction)	0.540
LOX	ELN	psi-mi:“MI:0407”(direct interaction)	0.540
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
	PLOD2	psi-mi:“MI:0914”(association)	0.530
ERBB2	HAX1	psi-mi:“MI:0914”(association)	0.530
GATAD2B	LOX	psi-mi:“MI:0915”(physical association)	0.440
GATAD2B	LOX	psi-mi:“MI:0403”(colocalization)	0.440
HSPA1A	LOX	psi-mi:“MI:0915”(physical association)	0.400
LOX	UXT	psi-mi:“MI:0915”(physical association)	0.370
LOX	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.370
COL1A1	LOX	psi-mi:“MI:0915”(physical association)	0.370
COL1A2	LOX	psi-mi:“MI:0915”(physical association)	0.370
COL3A1	LOX	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (54): RAF1 (Reconstituted Complex), LOX (Affinity Capture-MS), PTPRK (Affinity Capture-Western), PTPRK (Two-hybrid), LOX (Affinity Capture-Western), LOX (Affinity Capture-MS), LOX (Co-fractionation), ATP6V1A (Co-fractionation), LOX (Co-fractionation), LOX (Co-fractionation), ATP5C1 (Co-fractionation), LOX (Affinity Capture-MS), LOX (Affinity Capture-MS), LOX (Affinity Capture-MS), LOX (Affinity Capture-MS)

ESM2 similar proteins: A2A699, A2BD09, A6QLD2, A7YWH9, A8MVW0, A9L8T6, B0VX73, B1MT31, B4DS77, O14511, O35569, O35806, P16636, P28300, P28301, P33072, P54360, P56974, P97873, Q05063, Q08397, Q16650, Q2THW8, Q3UH99, Q3V1G4, Q499S9, Q5K027, Q5MJS3, Q5PQX1, Q5QQ37, Q64336, Q68BL7, Q68BL8, Q6PIX5, Q6QD51, Q701R2, Q766D5, Q76KP1, Q76M96, Q86X29

Diamond homologs: A1L0T3, A1L1V4, A1L4H1, A5PJQ2, A6H737, A7E3W2, B4F6N6, B5DF27, B8A4W9, E1C3U7, F1QQC3, F1RD85, G3V801, M9NDE3, O08762, O43866, O70513, P16636, P21757, P21758, P28300, P28301, P30203, P30204, P30205, P33072, P45845, P56730, P58022, P58215, P70117, P85521, P97873, Q05063, Q05585, Q07797, Q08380, Q08397, Q08B63, Q14DK5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
LOX	“up-regulates activity”	EFEMP2	binding
“CCT365623 (hydrochloride)”	“down-regulates activity”	LOX	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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
Molecules associated with elastic fibres	5	28.1×	2e-04
Interleukin-4 and Interleukin-13 signaling	7	13.1×	2e-04
Integrin cell surface interactions	5	12.2×	3e-03
Signaling by Interleukins	8	9.3×	3e-04
Cytokine Signaling in Immune system	8	5.9×	3e-03
Innate Immune System	9	4.2×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of cell cycle	5	24.2×	4e-04
collagen fibril organization	5	18.7×	8e-04
transforming growth factor beta receptor signaling pathway	6	15.9×	4e-04
response to ethanol	5	12.2×	3e-03
regulation of gene expression	6	8.3×	3e-03
heart development	6	7.9×	4e-03
transcription by RNA polymerase II	6	7.0×	6e-03
negative regulation of apoptotic process	9	5.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	15
Uncertain significance	336
Likely benign	194
Benign	12

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098840	NM_002317.7(LOX):c.53_66del (p.Leu18fs)	Pathogenic
1098842	NM_002317.7(LOX):c.445G>T (p.Gly149Ter)	Pathogenic
1339852	NM_002317.7(LOX):c.732_735del (p.Cys244fs)	Pathogenic
1411838	NC_000005.9:g.(?121409688)(121413680_?)del	Pathogenic
1763315	NM_002317.7(LOX):c.841del (p.Arg281fs)	Pathogenic
1785898	NM_002317.7(LOX):c.210_226dup (p.Val76fs)	Pathogenic
2017236	NM_002317.7(LOX):c.199C>T (p.Gln67Ter)	Pathogenic
2020787	NM_002317.7(LOX):c.667del (p.Gln223fs)	Pathogenic
2031883	NM_002317.7(LOX):c.88C>T (p.Gln30Ter)	Pathogenic
2045706	NM_002317.7(LOX):c.763dup (p.Arg255fs)	Pathogenic
2067815	NM_002317.7(LOX):c.460_461insCCCTGCGC (p.Leu154fs)	Pathogenic
2091974	NM_002317.7(LOX):c.63C>A (p.Cys21Ter)	Pathogenic
2424404	NC_000005.9:g.(?121402438)(121413680_?)del	Pathogenic
267291	NM_002317.7(LOX):c.839G>T (p.Ser280Ile)	Pathogenic
267293	NM_002317.7(LOX):c.800A>C (p.Gln267Pro)	Pathogenic
2746979	NM_002317.7(LOX):c.87_88delinsTT (p.Gln29_Gln30delinsHisTer)	Pathogenic
2767457	NM_002317.7(LOX):c.724G>T (p.Glu242Ter)	Pathogenic
2816479	NM_002317.7(LOX):c.40C>T (p.Gln14Ter)	Pathogenic
2844217	NM_002317.7(LOX):c.769dup (p.Tyr257fs)	Pathogenic
3222076	NM_002317.7(LOX):c.558C>G (p.Tyr186Ter)	Pathogenic
3642912	NM_002317.7(LOX):c.1035+1G>C	Pathogenic
3899267	NM_002317.7(LOX):c.713dup (p.Cys238fs)	Pathogenic
3907475	NM_002317.7(LOX):c.372G>A (p.Trp124Ter)	Pathogenic
4056321	NM_002317.7(LOX):c.1106_1109dup (p.Lys370fs)	Pathogenic
4098960	NM_002317.7(LOX):c.37_38del (p.Leu13fs)	Pathogenic
4614544	NM_002317.7(LOX):c.549T>A (p.Tyr183Ter)	Pathogenic
4724759	NM_002317.7(LOX):c.262del (p.Arg88fs)	Pathogenic
4726882	NM_002317.7(LOX):c.157C>T (p.Gln53Ter)	Pathogenic
1012735	NM_002317.7(LOX):c.960dup (p.Ala321fs)	Likely pathogenic
1708066	NM_002317.7(LOX):c.1024_1025dup (p.Gln345fs)	Likely pathogenic

SpliceAI

969 predictions. Top by Δscore:

Variant	Effect	Δscore
5:122070045:ACACT:A	donor_loss	1.0000
5:122070046:CACTT:C	donor_loss	1.0000
5:122070047:ACTTA:A	donor_loss	1.0000
5:122070048:CT:C	donor_loss	1.0000
5:122070049:TTA:T	donor_loss	1.0000
5:122070050:TA:T	donor_loss	1.0000
5:122070051:A:AC	donor_gain	1.0000
5:122070051:A:T	donor_loss	1.0000
5:122070052:C:CG	donor_gain	1.0000
5:122070052:CG:C	donor_gain	1.0000
5:122070052:CGG:C	donor_gain	1.0000
5:122070052:CGGT:C	donor_gain	1.0000
5:122070052:CGGTG:C	donor_gain	1.0000
5:122070488:CTTTA:C	donor_loss	1.0000
5:122070489:TTTAC:T	donor_loss	1.0000
5:122070490:TTAC:T	donor_loss	1.0000
5:122070492:ACC:A	donor_loss	1.0000
5:122070493:C:CA	donor_loss	1.0000
5:122070585:AATCC:A	acceptor_gain	1.0000
5:122070586:ATCC:A	acceptor_gain	1.0000
5:122070587:TCC:T	acceptor_gain	1.0000
5:122070588:CC:C	acceptor_gain	1.0000
5:122070588:CCC:C	acceptor_gain	1.0000
5:122070588:CCCTA:C	acceptor_loss	1.0000
5:122070589:CC:C	acceptor_gain	1.0000
5:122070590:C:CC	acceptor_gain	1.0000
5:122070590:C:T	acceptor_gain	1.0000
5:122070595:A:AC	acceptor_gain	1.0000
5:122070595:A:C	acceptor_gain	1.0000
5:122070600:C:CT	acceptor_gain	1.0000

AlphaMissense

2700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:122070065:C:G	C412S	1.000
5:122070066:A:T	C412S	1.000
5:122070106:A:C	C398W	1.000
5:122070107:C:G	C398S	1.000
5:122070108:A:G	C398R	1.000
5:122070108:A:T	C398S	1.000
5:122070157:G:C	N381K	1.000
5:122070157:G:T	N381K	1.000
5:122070498:A:G	L376P	1.000
5:122070525:G:A	T367I	1.000
5:122070532:C:G	D365H	1.000
5:122070536:C:A	W363C	1.000
5:122070536:C:G	W363C	1.000
5:122070538:A:G	W363R	1.000
5:122070538:A:T	W363R	1.000
5:122070542:G:C	C361W	1.000
5:122070543:C:A	C361F	1.000
5:122070543:C:G	C361S	1.000
5:122070543:C:T	C361Y	1.000
5:122070544:A:G	C361R	1.000
5:122070544:A:T	C361S	1.000
5:122070572:A:C	C351W	1.000
5:122070573:C:G	C351S	1.000
5:122070573:C:T	C351Y	1.000
5:122070574:A:G	C351R	1.000
5:122070574:A:T	C351S	1.000
5:122070589:C:G	G346R	1.000
5:122070589:C:T	G346R	1.000
5:122074028:A:C	C340W	1.000
5:122074029:C:G	C340S	1.000

dbSNP variants (sampled 300 via entrez): RS1000080738 (5:122079567 G>T), RS1000154204 (5:122079164 A>T), RS1000418950 (5:122066715 T>A), RS1000495294 (5:122066777 A>G), RS1000647921 (5:122074107 C>A,G,T), RS1000697834 (5:122064821 A>G), RS1000871605 (5:122072093 A>C), RS1001159475 (5:122078365 T>C), RS1001163597 (5:122079111 A>T), RS1001166914 (5:122063767 G>A,C), RS1001276673 (5:122078736 C>G,T), RS1001387919 (5:122071808 G>T), RS1002199838 (5:122065903 A>C), RS1002290247 (5:122072799 G>A), RS1002304467 (5:122065666 C>G)

Disease associations

OMIM: gene MIM:153455 | disease phenotypes: MIM:617168, MIM:607086

GenCC curated gene-disease

Disease	Classification	Inheritance
aortic aneurysm, familial thoracic 10	Strong	Autosomal dominant
familial thoracic aortic aneurysm and aortic dissection	Strong	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
familial thoracic aortic aneurysm and aortic dissection	Strong	AD

Mondo (7): aortic aneurysm, familial thoracic 10 (MONDO:0014950), cardiomyopathy (MONDO:0004994), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), breast ductal adenocarcinoma (MONDO:0005590), aortic aneurysm, familial thoracic 1 (MONDO:0024559), connective tissue disorder (MONDO:0003900), cutis laxa (MONDO:0016175)

Orphanet (4): Rare cardiomyopathy (Orphanet:167848), Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Familial aortic dissection (Orphanet:229), Cutis laxa (Orphanet:209)

HPO phenotypes

60 total (30 of 60 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000218	High palate
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000525	Abnormality iris morphology
HP:0000545	Myopia
HP:0000678	Dental crowding
HP:0000766	Abnormal sternum morphology
HP:0000767	Pectus excavatum
HP:0000822	Hypertension
HP:0000965	Cutis marmorata
HP:0000978	Bruising susceptibility
HP:0001065	Striae distensae
HP:0001166	Arachnodactyly
HP:0001297	Stroke
HP:0001382	Joint hypermobility
HP:0001519	Disproportionate tall stature
HP:0001640	Cardiomegaly
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001653	Mitral regurgitation
HP:0001659	Aortic regurgitation
HP:0001677	Coronary artery atherosclerosis
HP:0001712	Left ventricular hypertrophy
HP:0001763	Pes planus
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002138	Subarachnoid hemorrhage

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001859_25	Thiazide-induced adverse metabolic effects in hypertensive patients	8.000000e-06
GCST005580_17	Intraocular pressure	2.000000e-14
GCST005580_27	Intraocular pressure	6.000000e-14
GCST007431_45	Lung function (FEV1/FVC)	2.000000e-22
GCST007990_3	Coronary artery disease	3.000000e-09
GCST011011_52	Youthful appearance (self-reported)	4.000000e-11
GCST012226_60	Waist circumference adjusted for body mass index	5.000000e-08
GCST90000654_22	Central corneal thickness	5.000000e-13
GCST90013442_7	Keratoconus	2.000000e-20

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0004713	FEV/FVC ratio
EFO:0007789	BMI-adjusted waist circumference
EFO:0005213	central corneal thickness

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D009202	Cardiomyopathies	C14.280.238
D003240	Connective Tissue Diseases	C17.300
D003483	Cutis Laxa	C16.320.850.180; C17.300.230; C17.800.827.180
C562834	Aortic Aneurysm, Familial Thoracic 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2249 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 154,905 (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
CHEMBL93	ZILEUTON	4	21,372
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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
CCT365623	Inhibition	6.05	pIC50
compound 21b [PMID: 31430136]	Inhibition	5.48	pIC50

Binding affinities (BindingDB)

12 measured of 12 human assays (14 total across all organisms); most potent 12 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CN-DNJ	KI	200 nM
(2R,3R,4R,5S,6R)-2-(hydroxymethyl)-6-octylpiperidine-3,4,5-triol	KI	280 nM
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-nonylpiperidine-3,4,5-triol	KI	300 nM
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-octylpiperidine-3,4,5-triol	KI	420 nM
(2R,3R,5S,6R)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol	IC50	1000 nM
(2R,3S,4R,5R,6R)-2-hexyl-6-(hydroxymethyl)piperidine-3,4,5-triol	KI	2300 nM
(2R,3R,4R,5S)-1-hexyl-2-(hydroxymethyl)piperidine-3,4,5-triol	KI	5500 nM
(2R,3S,4R,5R,6R)-2-butyl-6-(hydroxymethyl)piperidine-3,4,5-triol	IC50	100000 nM
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-methylpiperidine-3,4,5-triol	IC50	150000 nM
(2R,3R,4R,5S,6R)-2-(hydroxymethyl)-6-propylpiperidine-3,4,5-triol	IC50	400000 nM
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-propylpiperidine-3,4,5-triol	IC50	700000 nM
(2R,3R,4R,5S,6R)-2-(hydroxymethyl)-6-methylpiperidine-3,4,5-triol	IC50	900000 nM

ChEMBL bioactivities

123 potent at pChembl≥5 of 151 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.72	IC50	190	nM	CHEMBL4444163
6.52	IC50	300	nM	CHEMBL4596739
6.50	IC50	320	nM	DISULFIRAM
6.47	IC50	340	nM	CHEMBL4458145
6.40	IC50	400	nM	CHEMBL4596503
6.38	IC50	420	nM	CHEMBL4536193
6.36	IC50	440	nM	CHEMBL4596022
6.35	IC50	450	nM	CHEMBL4596599
6.35	IC50	450	nM	CHEMBL4597756
6.33	IC50	470	nM	CHEMBL4595977
6.32	IC50	480	nM	CHEMBL4535726
6.29	IC50	510	nM	CHEMBL4453938
6.28	IC50	530	nM	CHEMBL4597283
6.26	IC50	550	nM	CHEMBL1618272
6.26	IC50	550	nM	CHEMBL4597684
6.23	IC50	590	nM	CHEMBL4595499
6.21	IC50	620	nM	CHEMBL4526964
6.16	IC50	690	nM	CHEMBL4597541
6.16	IC50	700	nM	CHEMBL4596464
6.14	IC50	720	nM	CHEMBL4595271
6.13	IC50	740	nM	CHEMBL4596703
6.12	IC50	760	nM	CHEMBL4597281
6.11	IC50	770	nM	CHEMBL4536971
6.11	IC50	770	nM	CHEMBL4528500
6.09	IC50	820	nM	CHEMBL4553578
6.08	IC50	830	nM	CHEMBL4598164
6.05	IC50	890	nM	CHEMBL4441173
6.04	IC50	910	nM	CHEMBL4594630
6.04	IC50	910	nM	CHEMBL4595035
6.03	IC50	930	nM	CHEMBL4459355
6.00	IC50	1000	nM	CHEMBL4443558
6.00	IC50	1000	nM	CHEMBL4571822
5.98	IC50	1040	nM	THIRAM
5.96	IC50	1100	nM	CHEMBL4596225
5.96	IC50	1100	nM	CHEMBL4594816
5.96	IC50	1100	nM	CHEMBL4541757
5.96	IC50	1100	nM	CHEMBL4564517
5.96	IC50	1100	nM	CHEMBL4596864
5.92	IC50	1200	nM	CHEMBL4469765
5.90	IC50	1260	nM	CHEMBL4457578
5.89	IC50	1300	nM	CHEMBL4596616
5.85	IC50	1400	nM	CHEMBL4526964
5.85	IC50	1400	nM	CHEMBL4597883
5.85	IC50	1400	nM	CHEMBL4596124
5.85	IC50	1400	nM	CHEMBL4457629
5.82	IC50	1500	nM	CHEMBL4595976
5.82	IC50	1500	nM	CHEMBL4472713
5.80	IC50	1600	nM	CHEMBL4241062
5.80	IC50	1600	nM	CHEMBL4597051
5.80	IC50	1600	nM	CHEMBL4456651

PubChem BioAssay actives

41 with measured affinity, of 91 total; 40 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
Disulfiram	1399349: Inhibition of recombinant human LOX expressed in HEK293 cells using diaminopentane as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorimetric method	ic50	0.3200	uM
3-aminopropanenitrile	1430573: Inhibition of full length recombinant human LOX expressed in HEK 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 in presence of BSA by Amplex red dye based fluorescence assay	ic50	0.5500	uM
(2R,3S,5R,6R)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol	1797728: In Vitro Enzyme Inhibition from Article 10.1016/j.bmc.2006.08.003: “Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.”	ic50	1.0000	uM
(2R,3R,4R,5S)-2-(hydroxymethyl)piperidine-3,4,5-triol	1797728: In Vitro Enzyme Inhibition from Article 10.1016/j.bmc.2006.08.003: “Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.”	ic50	1.0000	uM
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-methylpiperidine-3,4,5-triol	1797728: In Vitro Enzyme Inhibition from Article 10.1016/j.bmc.2006.08.003: “Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.”	ic50	1.0000	uM
dimethylcarbamothioylsulfanyl N,N-dimethylcarbamodithioate	1399349: Inhibition of recombinant human LOX expressed in HEK293 cells using diaminopentane as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorimetric method	ic50	1.0400	uM
1-[(Z)-4-amino-2-fluorobut-2-enyl]-3-[3-(dimethylsulfamoyl)phenyl]-2-methylindole-5-carboxylic acid;hydrochloride	1526681: Inhibition of LOX in human IMR90 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	1.2600	uM
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-nonylpiperidine-3,4,5-triol	1797728: In Vitro Enzyme Inhibition from Article 10.1016/j.bmc.2006.08.003: “Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.”	ic50	1.5000	uM
6-methyl-3-[(2E)-2-[(5-methyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)methylidene]hydrazinyl]-4H-1,2,4-triazin-5-one	1399349: Inhibition of recombinant human LOX expressed in HEK293 cells using diaminopentane as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorimetric method	ic50	1.6000	uM
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-(4-fluorophenyl)benzamide;hydrochloride	1483218: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	1.8000	uM
5-amino-N-[(E)-(4-hydroxyphenyl)methylideneamino]-1-(4-sulfamoylphenyl)pyrazole-4-carboxamide	2033699: Inhibition of LOX (unknown origin) using arachidonic/linoleic acid as substrate preincubated for 5 mins followed by substrate addition measured after 10 mins by absorbance based assay	ic50	1.9000	uM
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-octylpiperidine-3,4,5-triol	1797728: In Vitro Enzyme Inhibition from Article 10.1016/j.bmc.2006.08.003: “Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.”	ic50	2.1000	uM
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-(4-methoxyphenyl)benzamide;hydrochloride	1483218: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	2.4000	uM
5-amino-N-[(E)-benzylideneamino]-1-(4-sulfamoylphenyl)pyrazole-4-carboxamide	2033699: Inhibition of LOX (unknown origin) using arachidonic/linoleic acid as substrate preincubated for 5 mins followed by substrate addition measured after 10 mins by absorbance based assay	ic50	2.4000	uM
5-amino-1-(4-sulfamoylphenyl)-N-[(E)-thiophen-2-ylmethylideneamino]pyrazole-4-carboxamide	2033699: Inhibition of LOX (unknown origin) using arachidonic/linoleic acid as substrate preincubated for 5 mins followed by substrate addition measured after 10 mins by absorbance based assay	ic50	2.5000	uM
4,5-dimethyl-2-phenyl-4H-pyrazol-3-one	1399349: Inhibition of recombinant human LOX expressed in HEK293 cells using diaminopentane as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorimetric method	ic50	2.6000	uM
[3-[[4-(aminomethyl)-2-pyridinyl]oxy]phenyl]-(3,4-dihydro-1H-isoquinolin-2-yl)methanone	1483218: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	2.8000	uM
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-(1-benzothiophen-2-ylmethyl)benzamide;hydrochloride	1483218: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	2.9000	uM
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-benzylbenzamide;hydrochloride	1483218: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	3.1000	uM
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-phenylbenzamide;hydrochloride	1483218: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	3.1000	uM
5-amino-N-[(E)-(2-nitrophenyl)methylideneamino]-1-(4-sulfamoylphenyl)pyrazole-4-carboxamide	2033699: Inhibition of LOX (unknown origin) using arachidonic/linoleic acid as substrate preincubated for 5 mins followed by substrate addition measured after 10 mins by absorbance based assay	ic50	3.4000	uM
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-[(4-carbamimidoylphenyl)methyl]benzamide;dihydrochloride	1483218: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	3.5000	uM
5-amino-N-[(E)-(3-nitrophenyl)methylideneamino]-1-(4-sulfamoylphenyl)pyrazole-4-carboxamide	2033699: Inhibition of LOX (unknown origin) using arachidonic/linoleic acid as substrate preincubated for 5 mins followed by substrate addition measured after 10 mins by absorbance based assay	ic50	3.5000	uM
Zileuton	2033699: Inhibition of LOX (unknown origin) using arachidonic/linoleic acid as substrate preincubated for 5 mins followed by substrate addition measured after 10 mins by absorbance based assay	ic50	3.5000	uM
5-amino-N-[(E)-(2-chlorophenyl)methylideneamino]-1-(4-sulfamoylphenyl)pyrazole-4-carboxamide	2033699: Inhibition of LOX (unknown origin) using arachidonic/linoleic acid as substrate preincubated for 5 mins followed by substrate addition measured after 10 mins by absorbance based assay	ic50	3.8000	uM
(2R,3R,4R,5S)-1-hexyl-2-(hydroxymethyl)piperidine-3,4,5-triol	1797728: In Vitro Enzyme Inhibition from Article 10.1016/j.bmc.2006.08.003: “Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.”	ic50	4.0000	uM
5-amino-N-[(E)-(4-chlorophenyl)methylideneamino]-1-(4-sulfamoylphenyl)pyrazole-4-carboxamide	2033699: Inhibition of LOX (unknown origin) using arachidonic/linoleic acid as substrate preincubated for 5 mins followed by substrate addition measured after 10 mins by absorbance based assay	ic50	4.6000	uM
(2R,3R,4R,5S,6R)-2-(hydroxymethyl)-6-nonylpiperidine-3,4,5-triol	1797728: In Vitro Enzyme Inhibition from Article 10.1016/j.bmc.2006.08.003: “Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.”	ic50	4.8000	uM
5-amino-N-[(E)-[4-(dimethylamino)phenyl]methylideneamino]-1-(4-sulfamoylphenyl)pyrazole-4-carboxamide	2033699: Inhibition of LOX (unknown origin) using arachidonic/linoleic acid as substrate preincubated for 5 mins followed by substrate addition measured after 10 mins by absorbance based assay	ic50	4.8000	uM
5-amino-N-[(E)-(4-methoxyphenyl)methylideneamino]-1-(4-sulfamoylphenyl)pyrazole-4-carboxamide	2033699: Inhibition of LOX (unknown origin) using arachidonic/linoleic acid as substrate preincubated for 5 mins followed by substrate addition measured after 10 mins by absorbance based assay	ic50	4.8000	uM
5-amino-N-[(E)-(4-nitrophenyl)methylideneamino]-1-(4-sulfamoylphenyl)pyrazole-4-carboxamide	2033699: Inhibition of LOX (unknown origin) using arachidonic/linoleic acid as substrate preincubated for 5 mins followed by substrate addition measured after 10 mins by absorbance based assay	ic50	5.0000	uM
diethyl 5-[(5-amino-3-oxo-2-phenyl-1H-pyrazol-4-yl)diazenyl]-3-methylthiophene-2,4-dicarboxylate	1399349: Inhibition of recombinant human LOX expressed in HEK293 cells using diaminopentane as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorimetric method	ic50	5.0000	uM
(2R,3R,4R,5S,6R)-2-(hydroxymethyl)-6-octylpiperidine-3,4,5-triol	1797728: In Vitro Enzyme Inhibition from Article 10.1016/j.bmc.2006.08.003: “Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.”	ic50	5.0000	uM
Miglustat	1797728: In Vitro Enzyme Inhibition from Article 10.1016/j.bmc.2006.08.003: “Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.”	ic50	5.0000	uM
4-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-phenylbenzamide;hydrochloride	1483218: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	5.5000	uM
(2-chloro-4-pyridinyl)methanamine	1430573: Inhibition of full length recombinant human LOX expressed in HEK 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 in presence of BSA by Amplex red dye based fluorescence assay	ic50	5.9100	uM
3-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-(2-methoxyethyl)benzamide;hydrochloride	1483218: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	7.3000	uM
4-[[4-(aminomethyl)-2-pyridinyl]oxy]-N-(2-methoxyethyl)benzamide;hydrochloride	1483218: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	8.4000	uM
(2-phenoxy-4-pyridinyl)methanamine;hydrochloride	1483218: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay	ic50	8.7000	uM
(4Z)-4-(1-ethylquinolin-2-ylidene)-2-phenyl-5-phenyliminopyrazolidin-3-one	1399349: Inhibition of recombinant human LOX expressed in HEK293 cells using diaminopentane as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorimetric method	ic50	9.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Oxygen	decreases reaction, increases expression, increases activity	7
Estradiol	increases reaction, affects expression, affects binding, affects cotreatment, decreases expression (+1 more)	6
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	4
Valproic Acid	decreases expression, increases expression	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation	4
Particulate Matter	decreases expression, increases abundance, increases expression	4
bisphenol A	increases methylation, affects expression, decreases expression	3
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression	3
Arsenic	decreases ubiquitination, increases abundance, increases expression	3
Doxorubicin	decreases expression, increases expression, affects response to substance	3
Cyclosporine	decreases expression	3
nickel chloride	increases expression	2
cupric chloride	decreases expression, decreases reaction, increases activity	2
nickel sulfate	decreases expression, increases expression	2
GSK1210151A	decreases reaction, increases expression, decreases expression	2
Decitabine	affects expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Aminopropionitrile	decreases reaction, increases activity, decreases activity	2
Diethylhexyl Phthalate	increases expression, decreases expression	2
Hydrogen Peroxide	increases expression, affects expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Copper Sulfate	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
tremortin	increases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3997547	Binding	Inhibition of full length recombinant human LOX expressed in HEK 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 in presence	Small Molecule Lysyl Oxidase-like 2 (LOXL2) Inhibitors: The Identification of an Inhibitor Selective for LOXL2 over LOX. — ACS Med Chem Lett

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1W0	Abcam HeLa LOX KO	Cancer cell line	Female
CVCL_D1XC	Abcam A-549 LOX KO	Cancer cell line	Male
CVCL_D2BM	Abcam HCT 116 LOX KO	Cancer cell line	Male
CVCL_D2NM	Abcam THP-1 LOX KO	Cancer cell line	Male
CVCL_SV78	HAP1 LOX (-) 1	Cancer cell line	Male
CVCL_XQ21	HAP1 LOX (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	PHASE3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	PHASE3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	PHASE3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	PHASE3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	PHASE3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06846086	PHASE3	RECRUITING	Cardioprotective Effects of Melatonin in Patients With Cardiomyopathy
NCT07116473	PHASE3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)
NCT00185250	PHASE2	COMPLETED	Betaferon/ Betaseron (Interferon Beta-1b) in Patients With Chronic Viral Cardiomyopathy
NCT00490347	PHASE2	COMPLETED	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Feasibility Trial
NCT00694161	PHASE2	COMPLETED	The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy