LOXL2

Chr 8

lysyl oxidase like 2

Also known as: LOR, LOR2, WS9-14

NCBI Gene: 4017ENSG00000134013UniProt: Q9Y4K0

This gene encodes lysyl oxidase-like 2, a copper-dependent amine oxidase that catalyzes oxidative deamination of lysine residues in histones (particularly H3K4me3) and extracellular matrix proteins like collagen and elastin, functioning as both a transcriptional corepressor and extracellular matrix crosslinking enzyme. Mutations cause autosomal recessive osteogenesis imperfecta with bone fragility and connective tissue abnormalities. The gene is highly constrained against loss-of-function variation (LOEUF 0.65), indicating intolerance to protein-truncating mutations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
89
Pubs (1 yr)
81
P/LP submissions
0%
P/LP missense
0.65
LOEUF
DN
Mechanism· predicted
Clinical Summary— LOXL2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
81 unique Pathogenic / Likely Pathogenic· 154 VUS of 266 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.65LOEUF
pLI 0.000
Z-score 3.34
OE 0.44 (0.30–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.22Z-score
OE missense 0.97 (0.90–1.05)
483 obs / 497.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.30–0.65)
0≤0.351.4
Missense OE0.97 (0.90–1.05)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 18 / 41.1Missense obs/exp: 483 / 497.1Syn Z: -0.22
DN
0.6260th %ile
GOF
0.5366th %ile
LOF
0.3163th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

266 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic77
Likely Pathogenic4
VUS154
Likely Benign4
Benign3
77
Pathogenic
4
Likely Pathogenic
154
VUS
4
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
77
0
77
Likely Pathogenic
0
0
4
0
4
VUS
0
148
6
0
154
Likely Benign
0
2
2
0
4
Benign
0
1
0
2
3
Total0151892242

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LOXL2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Mesenchymal stem cell-derived exosomal miR-27b-3p alleviates liver fibrosis via downregulating YAP/LOXL2 pathway.
Cheng F et al.·J Nanobiotechnology
2023
Lysyl Oxidase (LOX) Family Members: Rationale and Their Potential as Therapeutic Targets for Liver Fibrosis.
Chen W et al.·Hepatology
2020Review
Identification of novel gene signature for lung adenocarcinoma by machine learning to predict immunotherapy and prognosis.
Shu J et al.·Front Immunol
2023
Machine learning-based in-silico analysis identifies signatures of lysyl oxidases for prognostic and therapeutic response prediction in cancer.
Xu Q et al.·Cell Commun Signal
2025
Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction.
Jheng JR et al.·Circulation
2024Functional
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Simtuzumab Attenuates Loxl2-Mediated Extracellular Matrix Remodeling and Preserves Cardiac Function in LMNA Mutation-Induced Dilated Cardiomyopathy.
Kervella M et al.·Circ Heart Fail
2026Functional
COL1A1-induced LOXL2 promotes ovarian cancer metastasis via a feedback loop upon inhibiting EGFR lysosomal degradation.
Shen Z et al.·Exp Mol Med
2026
Lysyl Oxidase LOXL2 Selectively Oxidizes Primary, α-Unbranched Amines and Prefers Cationic Substrates.
Poller LM et al.·Biochemistry
2026
Lupenone regulates LOXL2-mediated PANoptosis signaling through E3 ubiquitin ligases RNF168 to improve radiation-induced lung injury.
Wang SY et al.·Phytomedicine
2026
LOXL2 deletion triggers TMJ osteoarthritis, while overexpression protects it from NF-κB-induced chondrocyte apoptosis.
Raut RD et al.·Int J Oral Sci
2026Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients