LGR4 Gene

HGNC Family	G protein-coupled receptors
Name	leucine-rich repeat containing G protein-coupled receptor 4
Description	The protein encoded by this gene is a G-protein coupled receptor that binds R-spondins and activates the Wnt signaling pathway. This Wnt signaling pathway activation is necessary for proper development of many organs of the body. [provided by RefSeq, Oct 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LGR4 is a multifunctional, leucine‐rich repeat–containing G protein–coupled receptor that plays a pivotal role in modulating Wnt/β‐catenin signaling and other pathways in both development and adult tissue homeostasis. In the intestinal epithelium, for example, LGR4 works together with its homolog LGR5 to bind R‐spondin ligands; this interaction potentiates Wnt receptor activation (via enhanced LRP6 phosphorylation) and is essential for maintaining stem cell markers, crypt proliferation, and proper differentiation—even though the receptor appears to signal independently of traditional heterotrimeric G proteins ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in Wnt pathway potentiation, LGR4 serves as an alternative receptor for other ligands, such as RANKL, wherein it competes with the canonical RANK receptor to suppress RANKL‐induced osteoclast differentiation. By activating downstream signals (including Gαq and GSK3‐β pathways) that inhibit key osteoclastogenic transcription factors, LGR4 thereby contributes to bone homeostasis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n LGR4 is also critical in various developmental contexts. It has been implicated in the proper formation and remodeling of several organs: for instance, its expression is required for normal embryonic development of the gut, skin, kidney, and mammary gland—where it influences stem cell repopulation and ductal morphogenesis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "]. Moreover, disruption of LGR4 in animal models leads to malformations such as anterior segment dysgenesis in the eye and impaired tube elongation in the male reproductive tract, resulting in infertility due to defects in both testicular and epididymal structures ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, LGR4 can interact with intracellular scaffolds such as IQGAP1 to recruit components of the Wnt signaling complex and thereby amplify both canonical and noncanonical Wnt responses, underscoring its role as a key modulator of diverse signaling cascades ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "]. Additionally, emerging evidence suggests that LGR4 functions in the tumor microenvironment by promoting M2 polarization of tumor‐associated macrophages and facilitating cancer cell migration and invasion, which further highlights its multifaceted contributions to tissue physiology and disease ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "]. \n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wim de Lau, Nick Barker, Teck Y Low, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature10337"}], "href": "https://doi.org/10.1038/nature10337"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21727895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21727895"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kendra S Carmon, Xing Gong, Qiushi Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1106083108"}], "href": "https://doi.org/10.1073/pnas.1106083108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21693646"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21693646"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Roxana C Mustata, Tom Van Loy, Anne Lefort, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/embor.2011.52"}], "href": "https://doi.org/10.1038/embor.2011.52"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21508962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21508962"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jian Luo, Zhengfeng Yang, Yu Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LGR4 is a receptor for RANKL and negatively regulates osteoclast differentiation and bone resorption."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.4076"}], "href": "https://doi.org/10.1038/nm.4076"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27064449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27064449"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Bernd Kinzel, Monika Pikiolek, Vanessa Orsini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional roles of Lgr4 and Lgr5 in embryonic gut, kidney and skin development in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ydbio.2014.03.009"}], "href": "https://doi.org/10.1016/j.ydbio.2014.03.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24680895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24680895"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ying Wang, Jie Dong, Dali Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/stem.1438"}], "href": "https://doi.org/10.1002/stem.1438"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23712846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23712846"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jinsheng Weng, Jian Luo, Xuhong Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0708257105"}], "href": "https://doi.org/10.1073/pnas.0708257105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18424556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18424556"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Fernando Mendive, Patrick Laurent, Grégory Van Schoore, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defective postnatal development of the male reproductive tract in LGR4 knockout mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ydbio.2005.11.043"}], "href": "https://doi.org/10.1016/j.ydbio.2005.11.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16406039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16406039"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Takayuki Hoshii, Toru Takeo, Naomi Nakagata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LGR4 regulates the postnatal development and integrity of male reproductive tracts in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.106.054619"}], "href": "https://doi.org/10.1095/biolreprod.106.054619"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17079737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17079737"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Kendra S Carmon, Xing Gong, Jing Yi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RSPO-LGR4 functions via IQGAP1 to potentiate Wnt signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1323106111"}], "href": "https://doi.org/10.1073/pnas.1323106111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24639526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24639526"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Binghe Tan, Xiujuan Shi, Jie Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of Rspo-Lgr4 Facilitates Checkpoint Blockade Therapy by Switching Macrophage Polarization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-18-0152"}], "href": "https://doi.org/10.1158/0008-5472.CAN-18-0152"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29967265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29967265"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ryo Yamashita, Yumiko Takegawa, Machiko Sakumoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defective development of the gall bladder and cystic duct in Lgr4- hypomorphic mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.21900"}], "href": "https://doi.org/10.1002/dvdy.21900"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19301403"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19301403"}]}]}]}
Synonyms	BNMD17, GPR48
Proteins	LGR4_HUMAN
NCBI Gene ID	55366
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LGR4 has 9,871 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 119 datasets.

Click the + buttons to view associations for LGR4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LGR4 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 LGR4 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 LGR4 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 LGR4 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 LGR4 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 LGR4 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 LGR4 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 LGR4 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 LGR4 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 LGR4 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 LGR4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LGR4 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 LGR4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LGR4 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 LGR4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LGR4 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 LGR4 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 LGR4 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of LGR4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LGR4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LGR4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with LGR4 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 LGR4 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 LGR4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LGR4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with LGR4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with LGR4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by LGR4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for LGR4 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with LGR4 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 LGR4 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 LGR4 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 LGR4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LGR4 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 LGR4 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 LGR4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of LGR4 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 LGR4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of LGR4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with LGR4 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 LGR4 from the GeneSigDB Published Gene Signatures dataset.