LOX

Chr 5AD

lysyl oxidase

NCBI Gene: 4015ENSG00000113083UniProt: P28300

Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin (PubMed:26838787). Regulator of Ras expression. May play a role in tumor suppression. Plays a role in the aortic wall architecture (By similarity)

Primary Disease Associations & Inheritance

Aortic aneurysm, familial thoracic 10MIM #617168
AD
504
ClinVar variants
43
Pathogenic / LP
0.99
pLI score· haploinsufficient
4
Active trials
Clinical Summary— LOX
🧬
Gene-Disease Validity (ClinGen)
familial thoracic aortic aneurysm and aortic dissection · ADStrong

Strong evidence — appropriate for clinical testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 296 VUS of 504 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.988
Z-score 3.96
OE 0.09 (0.04–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.65Z-score
OE missense 0.88 (0.78–0.99)
205 obs / 233.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.09 (0.04–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.78–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
0≤1.21.6
LoF obs/exp: 2 / 22.1Missense obs/exp: 205 / 233.0Syn Z: -1.61

ClinVar Variant Classifications

504 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic11
VUS296
Likely Benign142
Benign5
Conflicting18
32
Pathogenic
11
Likely Pathogenic
296
VUS
142
Likely Benign
5
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
22
0
32
Likely Pathogenic
8
1
2
0
11
VUS
7
270
18
1
296
Likely Benign
0
6
33
103
142
Benign
0
1
4
0
5
Conflicting
—18
Total2527879104504

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

View in ClinVar →

Protein Context — Lollipop Plot

LOX · protein map & ClinVar variants

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

Gene2Phenotype Curations

LOX-related congenital cutis laxawith pulmonary failure and arterial tortuosity

limited
ARUndeterminedAltered Gene Product Structure
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
LYSYL OXIDASE; LOX
MIM #153455 · *

Aortic aneurysm, familial thoracic 10

MIM #617168

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — LOX
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Lysyl Oxidase (LOX) Family Members: Rationale and Their Potential as Therapeutic Targets for Liver Fibrosis.
Chen W et al.·Hepatology
2020Review
Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer.
Saatci O et al.·Nat Commun
2020
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
Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis.
Borsini A et al.·Mol Psychiatry
2021
Capsular polysaccharide enables Klebsiella pneumoniae to evade phagocytosis by blocking host-bacteria interactions.
Liu X et al.·mBio
2025
Macrophage-Specific E3 Ubiquitin Ligase TRIM31 Reduces Atherosclerotic Plaque Formation by Targeting LOX-1.
Zhang J et al.·Circulation
2026
Phospholipase iPLA(2)β averts ferroptosis by eliminating a redox lipid death signal.
Sun WY et al.·Nat Chem Biol
2021
Biosynthesis of leukotriene B(4).
Wan M et al.·Semin Immunol
2017Review
LOX-1 in Cardiovascular Disease: A Comprehensive Molecular and Clinical Review.
Sánchez-León ME et al.·Int J Mol Sci
2024Review
LOX-1 in atherosclerotic disease.
Sawamura T et al.·Clin Chim Acta
2015Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Cell metabolomics to reveal the mechanism of saponins and alkaloids on prostate inflammation via COX and LOX pathways.
Liu L et al.·Prostaglandins Other Lipid Mediat
2026Functional
Bifunctional Artificial Enzymes-Loaded Microgels With LOX- and CAT-Like Activities for Metabolic Reprogramming and Scarless Wound Repair.
Kang Y et al.·Adv Sci (Weinh)
2026Functional
Trientine ameliorates bleomycin-induced pulmonary fibrosis in rats through copper chelation and modulation of the CTR1/LOX/COL pathway.
Khalil IT et al.·Inflammopharmacology
2026
Chirality-controlled biomolecular recognition in Cu(I) metallodrugs: the first enantiomorphic CuP2O2 systems with dual DNA/LOX activity.
Hadjikakou SK et al.·Dalton Trans
2026
Tannic Acid Achieves Rapid Scar-Free Corneal Healing by Chelating Excess Copper to Suppress Aberrant LOX-Mediated Fibrosis.
Cai M et al.·Invest Ophthalmol Vis Sci
2026🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Lupus Erythematosus, Systemic

Omega-3 Supplementation in Systemic Lupus Erythematosus

NOT YET RECRUITING
NCT07393399Phase NAUniversity of Sao PauloStarted 2026-07
Omega-3 Fatty Acids (EPA plus DHA)Placebo
Keratoconus

The Collagen Factors of Rapid Progression of Keratoconus in Children.

RECRUITING
NCT06722937Zhongshan Ophthalmic Center, Sun Yat-sen UniversityStarted 2023-04-14
Observation
HIV-1-infection

DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection

RECRUITING
NCT06203132Phase PHASE3ANRS, Emerging Infectious DiseasesStarted 2025-01-27
Doravirine + tenofovir DF + lamivudineDolutegravir + tenofovir DF + lamivudine or emtricitabine
Colorectal Cancer

The Role of Lipid Transporter MFSD2A in the Resolution of Colorectal Cancer-associated Inflammation

RECRUITING
NCT06071598IRCCS San RaffaeleStarted 2023-03-15
Surgical specimens of CRC-affected patients

External Resources

Links to major genomics databases and tools