LNX1 Gene

HGNC Family	Zinc fingers
Name	ligand of numb-protein X 1, E3 ubiquitin protein ligase
Description	This gene encodes a membrane-bound protein that is involved in signal transduction and protein interactions. The encoded product is an E3 ubiquitin-protein ligase, which mediates ubiquitination and subsequent proteasomal degradation of proteins containing phosphotyrosine binding (PTB) domains. This protein may play an important role in tumorogenesis. Alternatively spliced transcript variants encoding distinct isoforms have been described. A pseudogene, which is located on chromosome 17, has been identified for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LNX1 (Ligand of Numb protein X) is a multifunctional RING‐type E3 ubiquitin ligase characterized by several PDZ domains and, in some isoforms, a unique N‐terminal RING finger. It acts as a molecular scaffold that binds to a variety of proteins to coordinate diverse cellular processes. For example, LNX1 specifically interacts with the phosphotyrosine‐binding (PTB) domain of Numb through a conserved LDNPAY motif; this interaction is thought to regulate cell fate decisions and modulate Notch signaling by targeting Numb for ubiquitin‐mediated degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, LNX1 can bind to the intracellular tail of the coxsackievirus and adenovirus receptor (CAR) via its PDZ domains, suggesting a role in assembling or stabilizing membrane‐associated protein complexes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, the p80 isoform of LNX1 (LNX1p80) has been implicated in the regulation of tight junction turnover. By interacting with claudin‐1, LNX1p80 promotes its polyubiquitylation, leading to enhanced endocytosis and subsequent lysosomal degradation of claudins—mechanisms essential for dynamic remodeling of tight junctions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " LNX1 is also reported to control the endocytosis of other transmembrane proteins such as JAM4 as part of a tripartite complex with Numb, thereby contributing to the reorganization of cell junctions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Finally, interactions with signaling proteins such as c‐Src, whose phosphorylation of LNX1 and subsequent ubiquitination by LNX1 have been observed, further underscore its role in modulating key signaling cascades that can impact cell proliferation and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the current body of work positions LNX1 as an important integrator of protein–protein interactions that links ubiquitin-mediated protein degradation to the regulation of cell fate, signaling pathways, and junctional dynamics. Its activity in directing the ubiquitination and turnover of proteins such as Numb and claudins underscores its potential impact on processes ranging from the modulation of Notch signaling to the remodeling of tight junctions, with broader implications for tissue homeostasis and pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S E Dho, S Jacob, C D Wolting, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mammalian numb phosphotyrosine-binding domain. Characterization of binding specificity and identification of a novel PDZ domain-containing numb binding protein, LNX."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (1998)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.273.15.9179"}], "href": "https://doi.org/10.1074/jbc.273.15.9179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9535908"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9535908"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Vivienne Armbruester, Marlies Sauter, Klaus Roemer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Np9 protein of human endogenous retrovirus K interacts with ligand of numb protein X."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.78.19.10310-10319.2004"}], "href": "https://doi.org/10.1128/JVI.78.19.10310-10319.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15367597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15367597"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kerstin Sollerbrant, Elisabeth Raschperger, Momina Mirza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Coxsackievirus and adenovirus receptor (CAR) forms a complex with the PDZ domain-containing protein ligand-of-numb protein-X (LNX)."}]}, {"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.M205927200"}], "href": "https://doi.org/10.1074/jbc.M205927200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12468544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12468544"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Senye Takahashi, Noriko Iwamoto, Hiroyuki Sasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The E3 ubiquitin ligase LNX1p80 promotes the removal of claudins from tight junctions in MDCK cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.040055"}], "href": "https://doi.org/10.1242/jcs.040055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19295125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19295125"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "A Kansaku, S Hirabayashi, H Mori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ligand-of-Numb protein X is an endocytic scaffold for junctional adhesion molecule 4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209468"}], "href": "https://doi.org/10.1038/sj.onc.1209468"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16832352"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16832352"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Andreas Weiss, Martin Baumgartner, Gerald Radziwill, et al. "}, {"type": "b", "children": [{"type": "t", "text": "c-Src is a PDZ interaction partner and substrate of the E3 ubiquitin ligase Ligand-of-Numb protein X1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2007.09.062"}], "href": "https://doi.org/10.1016/j.febslet.2007.09.062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17936276"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17936276"}]}]}]}
Synonyms	PDZRN2, LNX, MPDZ
Proteins	LNX1_HUMAN
NCBI Gene ID	84708
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LNX1 has 5,781 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 115 datasets.

Click the + buttons to view associations for LNX1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LNX1 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LNX1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of LNX1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of LNX1 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 LNX1 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 LNX1 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 LNX1 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 LNX1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of LNX1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LNX1 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 LNX1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LNX1 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 LNX1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LNX1 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 LNX1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with LNX1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of LNX1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LNX1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LNX1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with LNX1 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 LNX1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing LNX1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of LNX1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LNX1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with LNX1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with LNX1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with LNX1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by LNX1 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 LNX1 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 LNX1 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 LNX1 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 LNX1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LNX1 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 LNX1 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 LNX1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of LNX1 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 LNX1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with LNX1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with LNX1 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 LNX1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of LNX1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.