LRIG2 Gene

HGNC Family	Immunoglobulin superfamily domain containing
Name	leucine-rich repeats and immunoglobulin-like domains 2
Description	This gene encodes a transmembrane protein containing leucine-rich repeats and immunoglobulin-like domains. The encoded protein promotes epidermal growth factor signalling, resulting in increased proliferation. Its expression in the cytoplasm of glioma cells is correlated with poor survival. Mutations in this gene can cause urofacial syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LRIG2 is an evolutionarily conserved, single‐pass transmembrane glycoprotein characterized by extracellular leucine‐rich repeats and immunoglobulin‐like domains that is widely expressed in normal tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Functional studies have revealed that LRIG2 plays multiple context‐dependent roles. Mutations in LRIG2 have been linked to urofacial syndrome, where aberrant LRIG2 function in developing bladder nerves contributes to dysfunctional urinary voiding and an abnormal facial grimace."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In the nervous system, LRIG2 can associate with guidance receptors such as Neogenin, thereby negatively regulating ADAM17‐mediated proteolytic shedding; this regulation is essential for proper neurite growth, cortical neuron migration, and regenerative responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In various cancers, LRIG2 appears to promote oncogenic signaling. In hepatocellular carcinoma, for example, LRIG2 is upregulated via a long noncoding RNA/miRNA axis and contributes to enhanced proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In glioma and glioblastoma, LRIG2 functions in a pro-tumorigenic manner by augmenting receptor tyrosine kinase signaling. It not only promotes resistance to EGFR inhibition through stabilization of AXL and reactivation of downstream SRC signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", but also interacts with and potentiates PDGFRβ activation, thereby facilitating cell cycle progression and increased tumor cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Complementary studies in glioma further indicate that LRIG2, in contrast to its family member LRIG1, regulates receptor turnover and contributes to enhanced invasion and tumor cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Elevated cytoplasmic LRIG2 expression is also associated with aggressive disease and poor patient outcomes in other tumors. In oligodendroglioma, for instance, increased LRIG2 correlates independently with decreased survival"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and in invasive pituitary adenomas and early-stage cervical squamous cell carcinomas, high LRIG2 levels are linked to increased tumor invasiveness and reduced long-term survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, LRIG2 functions as a multifaceted modulator of cell signaling. By interacting with various receptor tyrosine kinases and influencing proteolytic processing events, it can promote oncogenic pathways and contribute to tumor aggressiveness as well as therapy resistance, while its mutation underlies specific congenital syndromes affecting bladder function.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Camilla Holmlund, Jonas Nilsson, Dongsheng Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization and tissue-specific expression of human LRIG2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2004.02.002"}], "href": "https://doi.org/10.1016/j.gene.2004.02.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15145052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15145052"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Helen M Stuart, Neil A Roberts, Berk Burgu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LRIG2 mutations cause urofacial syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.12.002"}], "href": "https://doi.org/10.1016/j.ajhg.2012.12.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23313374"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23313374"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Susan van Erp, Dianne M A van den Heuvel, Yuki Fujita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lrig2 Negatively Regulates Ectodomain Shedding of Axon Guidance Receptors by ADAM Proteases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2015.11.008"}], "href": "https://doi.org/10.1016/j.devcel.2015.11.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26651291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26651291"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Degang Ji, Yue Wang, Hang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA LINC00461/miR-149-5p/LRIG2 axis regulates hepatocellular carcinoma progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.03.049"}], "href": "https://doi.org/10.1016/j.bbrc.2019.03.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30879766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30879766"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Minhai Dong, Qungen Xiao, Jinyang Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting LRIG2 overcomes resistance to EGFR inhibitor in glioblastoma by modulating GAS6/AXL/SRC signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Gene Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41417-020-0163-1"}], "href": "https://doi.org/10.1038/s41417-020-0163-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31988476"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31988476"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Qungen Xiao, Minhai Dong, Fangling Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LRIG2 promotes the proliferation and cell cycle progression of glioblastoma cells in vitro and in vivo through enhancing PDGFRβ signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2018.4482"}], "href": "https://doi.org/10.3892/ijo.2018.4482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30015847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30015847"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Baofeng Wang, Lin Han, Rudong Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of LRIG2 expression by RNA interference inhibits glioblastoma cell (GL15) growth, causes cell cycle redistribution, increases cell apoptosis and enhances cell adhesion and invasion in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biol Ther (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cbt.8.11.8375"}], "href": "https://doi.org/10.4161/cbt.8.11.8375"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19421009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19421009"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Camilla Holmlund, Hannu Haapasalo, Wei Yi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytoplasmic LRIG2 expression is associated with poor oligodendroglioma patient survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropathology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1440-1789.2008.00970.x"}], "href": "https://doi.org/10.1111/j.1440-1789.2008.00970.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18992012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18992012"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Huaqiu Zhang, Qin Yan, Shutian Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of expression of Leucine-rich repeats and immunoglobulin-like domains 2 gene with invasiveness of pituitary adenoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Huazhong Univ Sci Technolog Med Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11596-011-0483-3"}], "href": "https://doi.org/10.1007/s11596-011-0483-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21823015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21823015"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Håkan Hedman, Annika K Lindström, Tibor Tot, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LRIG2 in contrast to LRIG1 predicts poor survival in early-stage squamous cell carcinoma of the uterine cervix."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Oncol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/0284186X.2010.492789"}], "href": "https://doi.org/10.3109/0284186X.2010.492789"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20553099"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20553099"}]}]}]}
Synonyms	LIG-2, UFS2
Proteins	LRIG2_HUMAN
NCBI Gene ID	9860
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LRIG2 has 5,437 functional associations with biological entities spanning 8 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) extracted from 108 datasets.

Click the + buttons to view associations for LRIG2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LRIG2 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 LRIG2 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 LRIG2 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 LRIG2 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 LRIG2 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 LRIG2 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 LRIG2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of LRIG2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LRIG2 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 LRIG2 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 LRIG2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LRIG2 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 LRIG2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with LRIG2 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LRIG2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LRIG2 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 LRIG2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with LRIG2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with LRIG2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing LRIG2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of LRIG2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LRIG2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LRIG2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing LRIG2 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 LRIG2 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 LRIG2 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 LRIG2 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 LRIG2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LRIG2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with LRIG2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of LRIG2 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 LRIG2 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 LRIG2 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 LRIG2 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 LRIG2 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 LRIG2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LRIG2 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 LRIG2 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 LRIG2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of LRIG2 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 LRIG2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.