LRIG3 Gene

HGNC Family	Immunoglobulin superfamily domain containing
Name	leucine-rich repeats and immunoglobulin-like domains 3
Description	Predicted to act upstream of or within otolith morphogenesis. Located in extracellular space. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LRIG3 is an integral transmembrane protein that plays multifaceted roles in both developmental morphogenesis and tumor suppression. In the developing inner ear, LRIG3 is essential for proper lateral semicircular canal formation by establishing a feedback loop with netrin‐1; this interaction precisely regulates basement membrane breakdown and thus canal morphogenesis (as demonstrated in."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the context of gliomas and glioblastomas, LRIG3 expression has been linked to a less aggressive tumor phenotype. Studies show that enhanced perinuclear localization of LRIG3 correlates with lower proliferative indices and improved clinical outcomes, while RNA interference–mediated knockdown of LRIG3 increases cell proliferation, invasion, adhesion, and resistance to apoptosis, likely through dysregulation of epidermal growth factor receptor (EGFR) signaling (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Consistent with these findings, forced LRIG3 expression in glioblastoma cells attenuates EGFR pathway activity and suppresses invasive behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, emerging evidence highlights a complex cross‐regulation within the LRIG family; LRIG1, for instance, can destabilize LRIG3, suggesting that the relative balance of these proteins is critical in fine‐tuning receptor tyrosine kinase signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Supporting its tumor‐suppressive role in diverse malignancies, LRIG3 overexpression in prostate cancer cells inhibits viability, adhesion, migration, and invasion while promoting apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Finally, LRIG3 has been shown to rescue defects in bone morphogenetic protein signaling and adipogenesis in LRIG‐null models, demonstrating broader roles in cellular differentiation and systemic metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore LRIG3’s importance as a key regulator of receptor-mediated signaling pathways that govern both normal tissue development and tumor suppression. Its ability to modulate EGFR and BMP signaling, along with its dynamic interplay with other LRIG family members, positions LRIG3 as a promising candidate for prognostic evaluation and therapeutic targeting in various human cancers and developmental disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Victoria E Abraira, Tony Del Rio, Andrew F Tucker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cross-repressive interactions between Lrig3 and netrin 1 shape the architecture of the inner ear."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.029330"}], "href": "https://doi.org/10.1242/dev.029330"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19004851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19004851"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dongsheng Guo, Jonas Nilsson, Hannu Haapasalo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-006-0032-5"}], "href": "https://doi.org/10.1007/s00401-006-0032-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16532360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16532360"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mingjun Cai, Lin Han, Rudong Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of LRIG3 gene expression via RNA interference modulates the proliferation, cell cycle, cell apoptosis, adhesion and invasion of glioblastoma cell (GL15)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2009.01.001"}], "href": "https://doi.org/10.1016/j.canlet.2009.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19200647"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19200647"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Dongsheng Guo, Hongkuan Yang, Yang Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LRIG3 modulates proliferation, apoptosis and invasion of glioblastoma cells as a potent tumor suppressor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jns.2015.02.015"}], "href": "https://doi.org/10.1016/j.jns.2015.02.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25708990"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25708990"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hanine Rafidi, Francisco Mercado, Michael Astudillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leucine-rich repeat and immunoglobulin domain-containing protein-1 (Lrig1) negative regulatory action toward ErbB receptor tyrosine kinases is opposed by leucine-rich repeat and immunoglobulin domain-containing protein 3 (Lrig3)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.486050"}], "href": "https://doi.org/10.1074/jbc.M113.486050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23723069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23723069"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ying Chen, Qing Wang, Mi Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpressed LRIG3 gene ameliorates prostate cancer through suppression of cell invasion and migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Macromol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ijbiomac.2018.11.028"}], "href": "https://doi.org/10.1016/j.ijbiomac.2018.11.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30412760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30412760"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Carl Herdenberg, Pascal M Mutie, Ola Billing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Commun Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42003-020-01613-w"}], "href": "https://doi.org/10.1038/s42003-020-01613-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33469151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33469151"}]}]}]}
Synonyms	LIG3
Proteins	LRIG3_HUMAN
NCBI Gene ID	121227
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LRIG3 has 5,704 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 109 datasets.

Click the + buttons to view associations for LRIG3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LRIG3 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 LRIG3 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 LRIG3 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 LRIG3 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 LRIG3 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 LRIG3 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 LRIG3 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 LRIG3 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 LRIG3 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 LRIG3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LRIG3 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 LRIG3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with LRIG3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LRIG3 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 LRIG3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LRIG3 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 LRIG3 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 LRIG3 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing LRIG3 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 LRIG3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LRIG3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing LRIG3 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 LRIG3 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 LRIG3 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 LRIG3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of LRIG3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LRIG3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with LRIG3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of LRIG3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by LRIG3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with LRIG3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with LRIG3 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 LRIG3 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 LRIG3 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 LRIG3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LRIG3 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 LRIG3 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 LRIG3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of LRIG3 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 LRIG3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with LRIG3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.