LRRFIP2 Gene

Name	leucine rich repeat (in FLII) interacting protein 2
Description	The protein encoded by this gene, along with MYD88, binds to the cytosolic tail of toll-like receptor 4 (TLR4), which results in activation of nuclear factor kappa B signaling. The ubiquitin-like protein FAT10 prevents the interaction of the encoded protein and TLR4, thereby inactivating the nuclear factor kappa B signaling pathway. In addition, this protein can downregulate the NLRP3 inflammasome by recruiting the caspase-1 inhibitor Flightless-I to the inflammasome complex. [provided by RefSeq, Jan 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LRRFIP2 is emerging as a multifunctional regulator that participates in diverse signaling pathways with important roles in immune modulation, developmental processes, and cancer. In the context of innate immunity, LRRFIP2 directly associates with the NLRP3 inflammasome where it binds to NLRP3 and recruits Flightless‐I—a pseudosubstrate inhibitor of caspase‐1—to suppress caspase‐1 activation and downstream interleukin‐1β maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, LRRFIP2 positively modulates Toll‐like receptor 4 (TLR4) signaling by interacting with the adaptor protein MyD88; its dynamic interaction is regulated by site‐specific phosphorylation (e.g., at serine 202), which in turn controls NF‐κB activation and cytokine production in LPS‐stimulated macrophages."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition to these immune functions, LRRFIP2 has been identified as an activator within the Wnt/β‐catenin pathway through its interaction with Dishevelled (Dvl), resulting in the stabilization of β‐catenin and activation of LEF/TCF‐dependent transcription, a process essential for proper embryonic development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Alterations in LRRFIP2 expression and splicing have also been reported in various cancers, with tumor‐specific splice variants and genomic rearrangements that encompass LRRFIP2 being associated with disease progression and even serving as potential diagnostic or prognostic markers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " Furthermore, variation in a genomic region spanning MLH1 and LRRFIP2 has been implicated as a modifier of disease onset in Huntington’s disease, suggesting that LRRFIP2 may contribute to genetic susceptibility in neurodegenerative conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jing Jin, Qian Yu, Chaofeng Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms3075"}], "href": "https://doi.org/10.1038/ncomms3075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23942110"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23942110"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Samuel J Carpentier, Minjian Ni, Jeffrey M Duggan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The signaling adaptor BCAP inhibits NLRP3 and NLRC4 inflammasome activation in macrophages through interactions with Flightless-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.aau0615"}], "href": "https://doi.org/10.1126/scisignal.aau0615"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31088976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31088976"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Penggao Dai, Sun Yong Jeong, Yanbao Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of TLR signaling by multiple MyD88-interacting partners including leucine-rich repeat Fli-I-interacting proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0802260"}], "href": "https://doi.org/10.4049/jimmunol.0802260"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19265123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19265123"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Harsha P Gunawardena, Yi Huang, Roma Kenjale, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unambiguous characterization of site-specific phosphorylation of leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) in Toll-like receptor 4 (TLR4)-mediated signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.168179"}], "href": "https://doi.org/10.1074/jbc.M110.168179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21220426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21220426"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jun Liu, Anne G Bang, Chris Kintner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the Wnt signaling activator leucine-rich repeat in Flightless interaction protein 2 by a genome-wide functional analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0409472102"}], "href": "https://doi.org/10.1073/pnas.0409472102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15677333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15677333"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kasper Thorsen, Karina D Sørensen, Anne Sofie Brems-Eskildsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M700590-MCP200"}], "href": "https://doi.org/10.1074/mcp.M700590-MCP200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18353764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18353764"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Manuela Pinheiro, Carla Pinto, Ana Peixoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel exonic rearrangement affecting MLH1 and the contiguous LRRFIP2 is a founder mutation in Portuguese Lynch syndrome families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Med (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/GIM.0b013e31821dd525"}], "href": "https://doi.org/10.1097/GIM.0b013e31821dd525"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21785361"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21785361"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kaili Chang, Chong Yuan, Xueguang Liu "}, {"type": "b", "children": [{"type": "t", "text": "A New RBPs-Related Signature Predicts the Prognosis of Colon Adenocarcinoma Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Oncol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fonc.2021.627504"}], "href": "https://doi.org/10.3389/fonc.2021.627504"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33767995"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33767995"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jong-Min Lee, Michael J Chao, Denise Harold, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A modifier of Huntington's disease onset at the MLH1 locus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddx286"}], "href": "https://doi.org/10.1093/hmg/ddx286"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28934397"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28934397"}]}]}]}
Synonyms	HUFI-2
Proteins	LRRF2_HUMAN
NCBI Gene ID	9209
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LRRFIP2 has 7,411 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, 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 LRRFIP2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LRRFIP2 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 LRRFIP2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LRRFIP2 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 LRRFIP2 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 LRRFIP2 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 LRRFIP2 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 LRRFIP2 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 LRRFIP2 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 LRRFIP2 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 LRRFIP2 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 LRRFIP2 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 LRRFIP2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with LRRFIP2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LRRFIP2 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 LRRFIP2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LRRFIP2 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 LRRFIP2 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 LRRFIP2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing LRRFIP2 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 LRRFIP2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing LRRFIP2 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 LRRFIP2 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 LRRFIP2 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 LRRFIP2 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 LRRFIP2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LRRFIP2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with LRRFIP2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by LRRFIP2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with LRRFIP2 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 LRRFIP2 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 LRRFIP2 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 LRRFIP2 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 LRRFIP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LRRFIP2 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 LRRFIP2 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 LRRFIP2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of LRRFIP2 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 LRRFIP2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with LRRFIP2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with LRRFIP2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of LRRFIP2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.