LOXL4 Gene

Name	lysyl oxidase-like 4
Description	This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LOXL4, a member of the lysyl oxidase enzyme family, is a copper‐dependent amine oxidase that catalyzes the cross‐linking of collagen and elastin, thereby contributing to extracellular matrix (ECM) maturation and remodeling. Its expression is regulated by factors such as transforming growth factor–β (TGF‑β), with studies in trabecular meshwork cells showing that induction of LOXL4 (along with other LOX isoforms) may increase ECM stiffness and outflow resistance, a mechanism relevant to ocular hypertension and glaucoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the context of cancer, LOXL4 is frequently upregulated and exerts multifaceted roles. For instance, in hepatocellular carcinoma, overexpression of LOXL4 promotes cell migration, invasion, metastatic dissemination, and angiogenesis via activation of the FAK/Src signaling pathway in a hydrogen peroxide–dependent manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In bladder cancer, LOXL4 is identified as a direct target of miR‑193a‑3p, acting as a key mediator in an oxidative stress signaling axis that modulates chemoresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Biochemical characterization has confirmed that LOXL4 possesses inherent amine oxidase activity, underscoring its fundamental role in ECM cross‐linking."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in gastric cancer, elevated LOXL4 levels correlate with enhanced tumor proliferation, invasion, and metastasis through similar activation of the FAK/Src pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while in breast cancer, reduced LOXL4 expression is linked to aberrant collagen deposition, altered collagen bundle structure, and ultimately promotes tumor growth and lung metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, during hepatocarcinogenesis, LOXL4 secreted by neoplastic cells can be internalized by hepatic macrophages, which then adopt an immunosuppressive phenotype that favors immune evasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, in colorectal cancer liver metastases with a replacement histopathological growth pattern, LOXL4 is notably expressed in neutrophils, suggesting its potential as a surrogate biomarker for this metastatic subtype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that LOXL4 critically regulates ECM composition and remodeling while modulating intracellular signaling pathways that influence tumor progression, metastasis, chemoresistance, and immune evasion. Such multifaceted functions underscore its potential as both a prognostic biomarker and a therapeutic target in diverse clinical settings.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Anirudh Sethi, Weiming Mao, Robert J Wordinger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transforming growth factor-beta induces extracellular matrix protein cross-linking lysyl oxidase (LOX) genes in human trabecular meshwork cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.11-7287"}], "href": "https://doi.org/10.1167/iovs.11-7287"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21546528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21546528"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rongkun Li, Yahui Wang, Xiaoxin Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosome-mediated secretion of LOXL4 promotes hepatocellular carcinoma cell invasion and metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12943-019-0948-8"}], "href": "https://doi.org/10.1186/s12943-019-0948-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30704479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30704479"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hui Deng, Lei Lv, Yang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the oxidative stress pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-13-234"}], "href": "https://doi.org/10.1186/1476-4598-13-234"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25311867"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25311867"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Moon Suk Kim, Sung-Su Kim, Sang Taek Jung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and purification of enzymatically active forms of the human lysyl oxidase-like protein 4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M308856200"}], "href": "https://doi.org/10.1074/jbc.M308856200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14551188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14551188"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rong-kun Li, Wen-yi Zhao, Fang Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lysyl oxidase-like 4 (LOXL4) promotes proliferation and metastasis of gastric cancer via FAK/Src pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-014-1823-z"}], "href": "https://doi.org/10.1007/s00432-014-1823-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25216702"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25216702"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sul Ki Choi, Hoe Suk Kim, Tiefeng Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LOXL4 knockdown enhances tumor growth and lung metastasis through collagen-dependent extracellular matrix changes in triple-negative breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.14450"}], "href": "https://doi.org/10.18632/oncotarget.14450"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28060764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28060764"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qing Li, Chun-Chao Zhu, Bo Ni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lysyl oxidase promotes liver metastasis of gastric cancer via facilitating the reciprocal interactions between tumor cells and cancer associated fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EBioMedicine (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ebiom.2019.10.037"}], "href": "https://doi.org/10.1016/j.ebiom.2019.10.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31678002"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31678002"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Vincent Palmieri, Anthoula Lazaris, Thomas Z Mayer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neutrophils expressing lysyl oxidase-like 4 protein are present in colorectal cancer liver metastases resistant to anti-angiogenic therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pathol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/path.5449"}], "href": "https://doi.org/10.1002/path.5449"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32297656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32297656"}]}]}]}
Synonyms	LOXC
Proteins	LOXL4_HUMAN
NCBI Gene ID	84171
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LOXL4 has 6,568 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 108 datasets.

Click the + buttons to view associations for LOXL4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LOXL4 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by LOXL4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of LOXL4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of LOXL4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of LOXL4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of LOXL4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LOXL4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LOXL4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LOXL4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LOXL4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of LOXL4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with LOXL4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LOXL4 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LOXL4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LOXL4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of LOXL4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of LOXL4 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing LOXL4 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LOXL4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LOXL4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing LOXL4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing LOXL4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with LOXL4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with LOXL4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LOXL4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with LOXL4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by LOXL4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with LOXL4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with LOXL4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with LOXL4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with LOXL4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LOXL4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at LOXL4 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LOXL4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of LOXL4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing LOXL4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with LOXL4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with LOXL4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing LOXL4 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of LOXL4 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of LOXL4 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.