LOXL1

Summary

LOXL1 (lysyl oxidase like 1, HGNC:6665) is a protein-coding gene on chromosome 15q24.1, encoding Lysyl oxidase homolog 1 (Q08397). Catalyzes the oxidative deamination of lysine and hydroxylysine residues in collagen and elastin, resulting in the formation of covalent cross-linkages, and the stabilization of collagen and elastin fibers.

This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. 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. Mutations in this gene are associated with exfoliation syndrome.

Source: NCBI Gene 4016 — RefSeq curated summary.

At a glance

• GWAS associations: 62
• Clinical variants (ClinVar): 99 total
• Phenotypes (HPO): 14
• Druggable target: yes
• MANE Select transcript: NM_005576

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6665
Approved symbol	LOXL1
Name	lysyl oxidase like 1
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Aliases	LOXL, LOL
Ensembl gene	ENSG00000129038
Ensembl biotype	protein_coding
OMIM	153456
Entrez	4016

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 2 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000261921, ENST00000562548, ENST00000566011, ENST00000566530, ENST00000567675, ENST00000856631

RefSeq mRNA: 1 — MANE Select: NM_005576 NM_005576

CCDS: CCDS10253

Canonical transcript exons

ENST00000261921 — 7 exons

Exon	Start	End
ENSE00001932826	73926462	73927885
ENSE00003550556	73942854	73942962
ENSE00003576071	73947807	73947902
ENSE00003615522	73949459	73949574
ENSE00003652706	73951831	73952136
ENSE00003655192	73947067	73947223
ENSE00003664690	73946417	73946554

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 98.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.9350 / max 649.6766, expressed in 1419 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147620	32.7224	1318
147622	5.5620	687
147624	2.4699	1039
147623	1.3315	438
147621	1.0907	546
147633	0.3794	248
147632	0.3792	232

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thoracic aorta	UBERON:0001515	98.10	gold quality
ascending aorta	UBERON:0001496	98.09	gold quality
descending thoracic aorta	UBERON:0002345	98.00	gold quality
stromal cell of endometrium	CL:0002255	97.96	gold quality
right coronary artery	UBERON:0001625	96.76	gold quality
aorta	UBERON:0000947	95.93	gold quality
urethra	UBERON:0000057	95.89	gold quality
left coronary artery	UBERON:0001626	95.31	gold quality
coronary artery	UBERON:0001621	95.02	gold quality
tibial artery	UBERON:0007610	94.35	gold quality
popliteal artery	UBERON:0002250	94.34	gold quality
saphenous vein	UBERON:0007318	94.16	gold quality
apex of heart	UBERON:0002098	93.51	gold quality
pigmented layer of retina	UBERON:0001782	92.86	gold quality
retina	UBERON:0000966	92.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.65	gold quality
metanephros cortex	UBERON:0010533	92.32	gold quality
gall bladder	UBERON:0002110	91.91	gold quality
adenohypophysis	UBERON:0002196	91.79	gold quality
right atrium auricular region	UBERON:0006631	91.61	gold quality
endocervix	UBERON:0000458	91.60	gold quality
cardiac atrium	UBERON:0002081	91.55	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.20	gold quality
blood vessel layer	UBERON:0004797	91.18	gold quality
smooth muscle tissue	UBERON:0001135	90.64	gold quality
ectocervix	UBERON:0012249	90.54	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.52	gold quality
heart	UBERON:0000948	90.36	gold quality
pituitary gland	UBERON:0000007	90.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.13	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	589.16
E-CURD-114	yes	62.28
E-HCAD-13	yes	25.58
E-ANND-3	yes	9.01
E-MTAB-7303	no	906.70
E-MTAB-10662	no	353.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting LOXL1, 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-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-548D-3P	99.87	70.67	4362
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-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-339-5P	96.73	66.01	820
HSA-MIR-4749-3P	96.40	66.24	798

Literature-anchored findings (GeneRIF, showing 40)

• comparison and aa sequence alignment of human and rat lysyl oxidase and human LOXL1 (PMID:12577300)
• pro-regions of lysyl oxidase and lysyl oxidase-like 1 are required for deposition onto elastic fibers (PMID:16251195)
• dill extract induces the LOXL gene expression in adult skin (PMID:16842595)
• The product of LOXL1 catalyzes the formation of elastin fibers found to be a major component of the lesions in exfoliation glaucoma (PMID:17690259)
• Genetic variation in LOXL1 might play a role as a risk factor for spontaneous cervical artery dissection. (PMID:17690546)
• Polymorphisms in the coding region of the LOXL1 gene located on chronosome 15q24 are associated with PXS and PEXG in population. (PMID:17891191)
• Levels of LOXL1 diminish with aging and were significantly decreased in the varicose condition. (PMID:17999374)
• These results confirm the previously detected association between LOXL1 and exfoliation syndrome. (PMID:18036875)
• Ancestral LOXL1 variants are associated with pseudoexfoliation in Caucasian Australians but with markedly lesser penetrance than in Nordic people. (PMID:18037624)
• LOXL1 single-nucleotide polymorphism variants are associated with pseudoexfoliation, but with a much lower prevalence of the G allele of rs1048661 in the Japanese population. (PMID:18201684)
• The SNPs rs1048661 and rs3825942 of the LOXL1 gene seem to be highly associated with XFS in the Japanese population, but a different polymorphism of LOXL1 may cause the development of XFS in the Japanese population. (PMID:18201684)
• The results from the present study do not indicate the involvement of the LOXL1 SNPs in primary open-angle and primary angle-closure glaucomas. (PMID:18223248)
• G153D LOXL1 variant is significantly associated with an increased risk of pseudoexfoliation and pseudoexfoliation glaucoma in an ethnically diverse patient population from the Northeastern United States (PMID:18254956)
• Two single-nucleotide polymorphism in the LOXL1 gene seem to be associated with exfoliation syndrome in the Japanese population (PMID:18282488)
• Our findings confirm genetic association of LOXL1 with Exfoliation glaucoma (XFG) and exfoliation syndrome and implicate a potential role of cross linking of elastin in the pathogenesis of XFG. (PMID:18287813)
• LOXL1 DNA sequence variants are associated with pseudoexfoliation will encourage new investigations into the role of elastin. (PMID:18332326)
• An analysis of LOXL1 and pseudoexfoliation glaucoma in a United States patient population was performed and confirmed the strong association previously reported for Icelandic and Swedish samples. (PMID:18334928)
• Out of the two non-synonymous single nucleotide polymorphisms in exon 1 of the LOXL1 gene, rs3825942 has a significant association with pseudoexfoliation syndrome cases in the patients of the southern Indian population. (PMID:18334947)
• Genetic variants in LOXL1 confer risk to PEX in German and Italian populations, independent of the presence of secondary glaucoma, confirming findings in patients from Northern Europe. (PMID:18385063)
• LOXL1 SNPs are located in 15q24.1 band and within genetic locus (GLC1N) associated with primary open-angle glaucoma (POAG). LOXL1 genetic predisposition is only limited to exfoliation with or without glaucoma and does not include POAG phenotype. (PMID:18385788)
• There was no association between SNPs in the LOXL1 gene and POAG. This is the first analysis of the LOXL1 gene in African-American and West-African populations. (PMID:18421074)
• Polymorphisms in the LOXL1 gene confer risk of pseudoexfoliation glaucoma and pseudoexfoliation glaucoma in Japanese, but with different risk-associated alleles and haplotypes. (PMID:18450598)
• These data confirm the previously reported association between LOXL1 polymorphisms and XFG and extend our knowledge to a Central European population. (PMID:18483563)
• Two mutations in lysyl oxidase-like 1 gene confer susceptibility to exfoliative glaucoma, primarily through exfoliation syndrome(XFS). Can we modulate LOXL1 activity to alter the course of XFS? (Review) (PMID:18541854)
• Genetic association studies were performed using a native Japanese population to examine the reproducibility of results of lysyl oxidase-like 1 (LOXL1) genetic association studies for exfoliation glaucoma (XFG) beyond the differences of ethnicity. (PMID:18552979)
• There was no involvement of the LOXL1 single nucleotide polymorphisms in patients with pigment dispersion syndrome and pigmentary glaucoma. (PMID:18618003)
• LOXL1 polymorphisms were associated with exfoliation syndrome. These polymorphisms had no influence on the phenotypic features of primary open-angle glaucoma patients. (PMID:18636115)
• Single nucleotide polymorphisms of LOXL1 (rs1048661; Arg141Leu and rs3825942; Gly153Asp) are highly associated with exfoliation syndrome in the Japanese population. (PMID:18648524)
• The association of lysyl oxidase like 1 (LOXL1) gene variants in Japanese patients with open-angle glaucoma, was evaluated. (PMID:18958304)
• Results provide evidence for lysyl oxidase-like 1 involvement in the initial stages of abnormal fibrogenesis in pseudoexfoliation syndrome tissues. (PMID:18974306)
• Individual LOXL1 single nucleotide polymorphisms, rs1048661, rs3825942, and rs2165241, were not associated with primary open-angle glaucoma in the Chinese population. (PMID:19098994)
• A functional single nucleotide polymorphism exists in the promoter region of the LOXL1 gene that does not contribute significantly to risk of pelvic organ prolapse or preterm premature rupture of membranes. (PMID:19182211)
• Pseudoexfoliation syndrome (XFS) is an important risk factor for glaucoma and lysyl oxidase-like 1 polymorphisms are strongly associated with XFS. (Review) (PMID:19240540)
• The earlier reported polymorphisms of the LOXL1 gene showed significant association also in the Finnish population. (PMID:19343041)
• Our study reveals that in the German population the LOXL1 genetic predisposition is limited to exfoliation glaucoma and does not include normal tension glaucoma. (PMID:19373106)
• There was decreased expression of fibulin-5 and increased expression of lysyl oxidase-like 1 in uterosacral ligaments in patients with pelvic organ prolapse, which suggests the possibility of defects in elastin synthesis. (PMID:19450918)
• Polymorphisms in LOXL1 confer risk to pseudoexfoliation syndrome (XFS) / pseudoexfoliation glaucoma (XFG) in the Chinese; the G allele of rs3825942 has been shown to be associated with XFS/XFG in all populations studied to date (PMID:19503743)
• Lysyl oxidase like 1 (LOXL1) on chromosome 15q24 is a major gene for exfoliation syndrome and exfoliation glaucoma. (Review) (PMID:19664108)
• 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)
• no consistent pattern among sites in the vagina in pelvic organ prolapse (PMID:19763368)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	loxl1	ENSDARG00000054451
mus_musculus	Loxl1	ENSMUSG00000032334
rattus_norvegicus	Loxl1	ENSRNOG00000008680

Paralogs (15): CD6 (ENSG00000013725), CD5L (ENSG00000073754), LGALS3BP (ENSG00000108679), CD5 (ENSG00000110448), LOX (ENSG00000113083), LOXL3 (ENSG00000115318), LOXL2 (ENSG00000134013), LOXL4 (ENSG00000138131), SSC4D (ENSG00000146700), PRSS12 (ENSG00000164099), CD163 (ENSG00000177575), CD163L1 (ENSG00000177675), SSC5D (ENSG00000179954), DMBT1 (ENSG00000187908), SCART1 (ENSG00000214279)

Protein

Protein identifiers

Lysyl oxidase homolog 1 — Q08397 (reviewed: Q08397)

Alternative names: Lysyl oxidase-like protein 1

All UniProt accessions (2): Q08397, H3BUV8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidative deamination of lysine and hydroxylysine residues in collagen and elastin, resulting in the formation of covalent cross-linkages, and the stabilization of collagen and elastin fibers. Essential for the elastic fiber homeostasis and for their maintenance at adult age.

Subunit / interactions. Interacts (via propeptide) with EFEMP2. Interacts with FBLN5.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in ocular tissues including the iris, ciliary body, lens and optic nerve. Not detected in the retina.

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. Proteolytic processing by a furin-like protease causes removal of N-terminal propeptide resulting in an enzyme largely inactive, but further proteolytic processing by BMP1 results in enzyme activation.

Disease relevance. Exfoliation syndrome (XFS) [MIM:177650] A disorder characterized by accumulation of abnormal fibrillar deposits in the anterior segment of the eye. In addition to being a cause of glaucoma and glaucomatous optic neuropathy, exfoliation syndrome has also been associated with lens zonule weakness, cataract formation, and systemic vascular complications due to deposition of exfoliation material in extraocular tissues. Disease susceptibility is associated with variants affecting the gene represented in this entry. Susceptibility to exfoliation syndrome is conferred by a risk haplotype that includes two LOXL1 coding non-synonymous SNPs (Arg141Leu and Gly153Asp) and one intronic SNP. Arg141Leu and Gly153Asp are sufficient to confer disease susceptibility in some populations.

Cofactor. Contains 1 lysine tyrosylquinone.

Similarity. Belongs to the lysyl oxidase family.

RefSeq proteins (1): NP_005567* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001695	Lysyl_oxidase	Family
IPR019828	Lysyl_oxidase_CS	Conserved_site
IPR050912

Pfam: PF01186

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (27 total): site 5, disulfide bond 5, region of interest 4, binding site 3, compositionally biased region 3, sequence variant 2, signal peptide 1, propeptide 1, modified residue 1, chain 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08397-F1	59.91	0.32

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 (5): 95–96 (cleavage; by furin-like protease); 134–135 (cleavage; by bmp1); 151–152 (cleavage; by bmp1); 216–217 (cleavage; by adamts14); 337–338 (cleavage; by bmp1)

Ligand- & substrate-binding residues (3): 449; 451; 453

Post-translational modifications (2): 512, 477–512

Disulfide bonds (5): 395–401, 448–497, 481–487, 508–518, 555–569

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: 204 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, PAL_PRMT5_TARGETS_UP, GOCC_SECRETORY_GRANULE, GOZGIT_ESR1_TARGETS_DN, GNF2_PTX3, GOBP_ARTERY_DEVELOPMENT, CAGCTG_AP4_Q5, CLASPER_LYMPHATIC_VESSELS_DURING_METASTASIS_DN, SREBP1_02, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_AORTA_DEVELOPMENT, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1

GO Biological Process (4): protein deamination (GO:0018277), collagen fibril organization (GO:0030199), response to lipopolysaccharide (GO:0032496), aorta development (GO:0035904)

GO Molecular Function (6): protein-lysine 6-oxidase activity (GO:0004720), copper ion binding (GO:0005507), 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 (5): acrosomal vesicle (GO:0001669), extracellular region (GO:0005576), basement membrane (GO:0005604), 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
protein modification process	1
extracellular matrix organization	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
artery development	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
binding	1
catalytic activity	1
oxidoreductase activity, acting on the CH-NH2 group of donors	1
cation binding	1
secretory granule	1
cellular anatomical structure	1
extracellular matrix	1
external encapsulating structure	1

Protein interactions and networks

STRING

1610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LOXL1	FBLN5	Q9UBX5	991
LOXL1	ELN	P15502	928
LOXL1	LTBP2	Q14767	823
LOXL1	LTBP3	Q9NS15	813
LOXL1	SERPINB1	P30740	790
LOXL1	FBN1	P35555	776
LOXL1	CLU	P10909	686
LOXL1	LTBP1	P22064	670
LOXL1	MFAP2	P55001	664
LOXL1	EFEMP1	Q12805	631
LOXL1	EFEMP2	O95967	607
LOXL1	BMP1	P13497	541
LOXL1	MFAP5	Q13361	540
LOXL1	MYOC	Q99972	514
LOXL1	APOE	P02649	507

IntAct

21 interactions, top by confidence:

A	B	Type	Score
BCHE	ENTPD5	psi-mi:“MI:0914”(association)	0.640
LOXL1	FBLN5	psi-mi:“MI:0407”(direct interaction)	0.440
GATAD2B	LOXL1	psi-mi:“MI:0915”(physical association)	0.400
ATXN1	LOXL1	psi-mi:“MI:0915”(physical association)	0.370
LOXL1	TFAP2A	psi-mi:“MI:0915”(physical association)	0.370
LOXL1	TFAP2C	psi-mi:“MI:0915”(physical association)	0.370
NUDCD1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
NUDCD1	APOBEC3B	psi-mi:“MI:0914”(association)	0.350
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
BCHE		psi-mi:“MI:0914”(association)	0.350
A2M	PZP	psi-mi:“MI:0914”(association)	0.350
BCHE	SHTN1	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
TRIM68	BTN3A3	psi-mi:“MI:0914”(association)	0.350
CD160	PLXNB2	psi-mi:“MI:0914”(association)	0.350
A2M	BMP7	psi-mi:“MI:0914”(association)	0.350
LOXL1	KLHDC10	psi-mi:“MI:0914”(association)	0.350
MFAP4	QSOX1	psi-mi:“MI:0914”(association)	0.350
TRIM68	NRP2	psi-mi:“MI:0914”(association)	0.350
P4HA2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): LOXL1 (Affinity Capture-MS), LOXL1 (Affinity Capture-MS), FBLN5 (Reconstituted Complex), FBLN5 (Affinity Capture-Western), FBLN5 (Two-hybrid), KCNIP1 (Affinity Capture-MS), LOXL1 (Affinity Capture-MS), LOXL1 (Affinity Capture-MS), LOXL1 (Affinity Capture-MS), LOXL1 (Affinity Capture-MS), KLHDC10 (Affinity Capture-MS), LOXL1 (Affinity Capture-MS), LOXL1 (Affinity Capture-MS), LOXL1 (Affinity Capture-MS), LOXL1 (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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	2
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1285 predictions. Top by Δscore:

Variant	Effect	Δscore
15:73927883:GCG:G	donor_gain	1.0000
15:73927884:CGGTG:C	donor_loss	1.0000
15:73927886:G:GG	donor_gain	1.0000
15:73927887:T:G	donor_loss	1.0000
15:73946415:A:AG	acceptor_gain	1.0000
15:73946416:G:GG	acceptor_gain	1.0000
15:73946534:G:GT	donor_gain	1.0000
15:73946552:CCA:C	donor_gain	1.0000
15:73946555:G:GG	donor_gain	1.0000
15:73947058:T:A	acceptor_gain	1.0000
15:73947065:A:AG	acceptor_gain	1.0000
15:73947065:AG:A	acceptor_gain	1.0000
15:73947066:G:GT	acceptor_gain	1.0000
15:73947066:GG:G	acceptor_gain	1.0000
15:73947066:GGC:G	acceptor_gain	1.0000
15:73947066:GGCA:G	acceptor_gain	1.0000
15:73947066:GGCAT:G	acceptor_gain	1.0000
15:73947196:GCGC:G	donor_gain	1.0000
15:73947199:C:G	donor_gain	1.0000
15:73947804:CA:C	acceptor_loss	1.0000
15:73947805:A:AC	acceptor_loss	1.0000
15:73947805:A:AG	acceptor_gain	1.0000
15:73947805:AG:A	acceptor_gain	1.0000
15:73947805:AGG:A	acceptor_gain	1.0000
15:73947806:G:A	acceptor_gain	1.0000
15:73947806:G:GA	acceptor_gain	1.0000
15:73947806:GGG:G	acceptor_gain	1.0000
15:73947806:GGGC:G	acceptor_gain	1.0000
15:73947806:GGGCC:G	acceptor_gain	1.0000
15:73947902:GGTG:G	donor_loss	1.0000

AlphaMissense

3689 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:73926916:T:A	W45R	1.000
15:73926916:T:C	W45R	1.000
15:73926918:G:C	W45C	1.000
15:73926918:G:T	W45C	1.000
15:73942934:T:A	C395S	1.000
15:73942934:T:C	C395R	1.000
15:73942935:G:A	C395Y	1.000
15:73942935:G:C	C395S	1.000
15:73942936:T:G	C395W	1.000
15:73942952:T:A	C401S	1.000
15:73942952:T:C	C401R	1.000
15:73942953:G:C	C401S	1.000
15:73942954:T:G	C401W	1.000
15:73946461:T:C	L419P	1.000
15:73946464:T:C	L420P	1.000
15:73946470:T:C	F422S	1.000
15:73946470:T:G	F422C	1.000
15:73946489:C:A	N428K	1.000
15:73946489:C:G	N428K	1.000
15:73946493:G:C	G430R	1.000
15:73946493:G:T	G430C	1.000
15:73946505:T:C	F434L	1.000
15:73946506:T:C	F434S	1.000
15:73946506:T:G	F434C	1.000
15:73946507:C:A	F434L	1.000
15:73946507:C:G	F434L	1.000
15:73946532:T:A	W443R	1.000
15:73946532:T:C	W443R	1.000
15:73946534:G:C	W443C	1.000
15:73946534:G:T	W443C	1.000

dbSNP variants (sampled 300 via entrez): RS1000079370 (15:73946057 G>A), RS1000176179 (15:73933169 A>G), RS1000274809 (15:73939102 T>C), RS1000288591 (15:73926559 G>C), RS1000306095 (15:73938840 C>T), RS1000374347 (15:73942342 A>G), RS1000481730 (15:73948825 A>G), RS1000609064 (15:73940582 G>A), RS1000621164 (15:73928124 G>A), RS1000916166 (15:73934436 A>C), RS1000923801 (15:73928371 G>A), RS1001027577 (15:73924462 G>A,C,T), RS1001416574 (15:73951418 G>A), RS1001507 (15:73944612 G>A,T), RS1001624268 (15:73945643 G>T)

Disease associations

OMIM: gene MIM:153456 | disease phenotypes: MIM:177650

GenCC curated gene-disease

Mondo (1): exfoliation syndrome, susceptibility to (MONDO:0100046)

Orphanet (0):

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000501	Glaucoma
HP:0000517	Abnormal lens morphology
HP:0000518	Cataract
HP:0001132	Lens subluxation
HP:0002063	Rigidity
HP:0009916	Anisocoria
HP:0011499	Mydriasis
HP:0012627	Pseudoexfoliation
HP:0012629	Phakodonesis
HP:0012631	Pigment deposition in the trabecular meshwork
HP:0012633	Asymmetry of intraocular pressure
HP:0012635	Iris hypoperfusion
HP:0012636	Retinal venous occlusion

GWAS associations

62 associations (top):

Study	Trait	p-value
GCST000067_1	Glaucoma (exfoliation)	3.000000e-21
GCST000442_3	Aortic root size	3.000000e-06
GCST001956_43	Height	7.000000e-09
GCST002486_2	Exfoliation glaucoma or exfoliation syndrome	3.000000e-84
GCST002787_2	Exfoliation syndrome	5.000000e-29
GCST002787_3	Exfoliation syndrome	2.000000e-217
GCST003998_8	Joint mobility (Beighton score)	3.000000e-10
GCST004063_144	Waist circumference adjusted for body mass index	3.000000e-10
GCST004063_148	Waist circumference adjusted for body mass index	6.000000e-12
GCST004500_19	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-09
GCST004500_83	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-10
GCST004501_107	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	8.000000e-11
GCST004501_108	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-10
GCST004503_6	Waist circumference adjusted for BMI in smokers	4.000000e-07
GCST004504_79	Waist circumference adjusted for BMI in non-smokers	5.000000e-06
GCST004504_80	Waist circumference adjusted for BMI in non-smokers	2.000000e-08
GCST004562_114	Waist circumference adjusted for body mass index	2.000000e-10
GCST004562_149	Waist circumference adjusted for body mass index	7.000000e-11
GCST004562_235	Waist circumference adjusted for body mass index	1.000000e-09
GCST004562_45	Waist circumference adjusted for body mass index	4.000000e-10
GCST004562_61	Waist circumference adjusted for body mass index	1.000000e-09
GCST004563_131	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-09
GCST004563_18	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-09
GCST004563_198	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-09
GCST004563_26	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	3.000000e-10
GCST004563_49	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	6.000000e-10
GCST004564_235	Waist circumference adjusted for BMI in active individuals	2.000000e-08
GCST004564_3	Waist circumference adjusted for BMI in active individuals	4.000000e-09
GCST004564_4	Waist circumference adjusted for BMI in active individuals	6.000000e-09
GCST004564_5	Waist circumference adjusted for BMI in active individuals	5.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007905	joint hypermobility measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0006941	grip strength measurement
EFO:0009959	diverticular disease
EFO:0004341	body fat distribution
EFO:0006939	cup-to-disc ratio measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523279 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.65	IC50	2260	nM	CHEMBL4457578

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 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	1526683: Inhibition of recombinant human LOXL1 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	2.2600	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression	7
sodium arsenite	increases abundance, increases expression, affects methylation, decreases expression, affects cotreatment	5
Estradiol	increases expression, increases reaction, affects cotreatment	4
Valproic Acid	increases expression, increases methylation, affects expression, decreases expression	4
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
entinostat	increases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrimidifen	decreases expression	1
thifluzamide	decreases expression	1
pyrachlostrobin	decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
picoxystrobin	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 expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Aerosols	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	increases expression	1
Antimycin A	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4323286	Binding	Inhibition of recombinant human LOXL1 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	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_D1TH	Abcam U-87MG LOXL1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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