HGNC Family | CD molecules (CD), Immunoglobulin superfamily domain containing |
Name | leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), member 3 |
Description | This gene encodes a member of a family of immunoreceptors that are expressed predominantly in monocytes and B cells, and at lower levels in dendritic cells and natural killer cells. The encoded protein lacks the transmembrane region found in other members of this family. It acts as a soluble receptor for class I major histocompatibility complex (MHC) antigens. Alternatively spliced transcript variants encoding different isoforms have been found. This gene is located in a cluster of related genes on chromosome 19 and is polymorphic in human populations, with many individuals containing a deletion of this genomic region. [provided by RefSeq, Mar 2014] |
Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nLILRA3 is a unique member of the leukocyte immunoglobulin‐like receptor family because it is secreted rather than membrane bound. Structural and sequence‐based studies have revealed that LILRA3 lacks transmembrane and cytoplasmic domains, and that several polymorphic residues in its immunoglobulin‐like domains likely affect its ligand‐binding properties. Indeed, biochemical analyses indicate that, unlike other LILRs that bind folded HLA class I molecules, LILRA3 preferentially interacts with free heavy chain (for example, HLA‐C free chains) and shows overall reduced binding affinity relative to its membrane‐bound homologues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctionally, LILRA3 appears to play an important role in modulating immune responses. Several genetic studies have linked the presence or deletion of the LILRA3 gene with susceptibility to autoimmune and inflammatory disorders. For example, loss‐of‐function alleles or homozygous deletions are associated with higher incidence and an earlier onset of diseases such as multiple sclerosis, Sjögren’s syndrome, and rheumatoid arthritis. In vitro analyses demonstrate that exogenous LILRA3 can bind to monocytes and B cells, triggering the secretion of cytokines and stimulating proliferation of cytotoxic lymphocytes (including CD8⁺ T cells and natural killer cells). By acting as a competitive agonist/antagonist relative to activating LILR receptors, LILRA3 helps to balance activating and inhibitory immune signals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "16"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its immunomodulatory role in autoimmunity, LILRA3 has been implicated in a variety of other pathological contexts. In neuroimmunology, soluble LILRA3 binds with high affinity to Nogo‐66—a myelin‐associated inhibitor—and by doing so it antagonizes inhibitory signaling, thereby promoting neurite outgrowth and synaptogenesis through the ERK/MEK pathway. In addition, altered LILRA3 expression is linked not only to multiple sclerosis severity but also to conditions with inflammatory components such as benign prostatic hyperplasia, nasopharyngeal carcinoma, and antiphospholipid syndrome. Its modulatory actions also extend to infectious diseases where LILRA3 regulation appears to influence cytotoxic cell proliferation in HIV infection. Moreover, over‐expression studies in monocytes have shown that LILRA3 can dampen the secretion of pro‐inflammatory cytokines while enhancing phagocytosis and cell proliferation via Akt and Erk/MEK pathways, as seen in inflammatory bowel disease. Finally, genetic interactions with other loci—including those in Takayasu arteritis and systemic lupus erythematosus—underscore the broader importance of LILRA3 in regulating inflammatory and immune homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "29"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S J Moodie, P J Norman, A L King, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Leukocyte immunoglobulin-like receptor A3 is increased in IBD patients and functions as an anti-inflammatory modulator."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Immunol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cei.13529"}], "href": "https://doi.org/10.1111/cei.13529"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33006756"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33006756"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Mengyan Wang, Mengru Liu, Jinchao Jia, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A susceptibility locus in the IL12B but not LILRA3 region is associated with vascular damage in Takayasu arteritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-93213-9"}], "href": "https://doi.org/10.1038/s41598-021-93213-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34211061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34211061"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Hongjiang Liu, Chun Li, Hui Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Soluble LILRA3 is aberrantly expressed in antiphospholipid syndrome (APS) and is a potential marker of thrombotic APS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Rheumatology (Oxford) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/rheumatology/keac192"}], "href": "https://doi.org/10.1093/rheumatology/keac192"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35325077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35325077"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Mengru Liu, Yundi Tang, Yan Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leukocyte Ig-like receptor A3 facilitates inflammation, migration and invasion of synovial tissue-derived fibroblasts via ERK/JNK activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Rheumatology (Oxford) (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/rheumatology/kead359"}], "href": "https://doi.org/10.1093/rheumatology/kead359"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37462532"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37462532"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Wei Tian, Li Xin Li, Wen Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leukocyte immunoglobulin-like receptor A3 gene deletion in five Chinese populations and protective association with nasopharyngeal carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Immunogenet (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/iji.12647"}], "href": "https://doi.org/10.1111/iji.12647"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38015196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38015196"}]}]}]}
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Synonyms | ILT6, ILT-6, LIR-4, LIR4, CD85E, HM43, HM31 |
Proteins | LIRA3_HUMAN |
NCBI Gene ID | 11026 |
API | |
Download Associations | |
Predicted Functions |
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Co-expressed Genes |
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Expression in Tissues and Cell Lines |
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LILRA3 has 2,242 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 71 datasets.
Click the + buttons to view associations for LILRA3 from the datasets below.
If available, associations are ranked by standardized value
Dataset | Summary | |
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Achilles Cell Line Gene Essentiality Profiles | cell lines with fitness changed by LILRA3 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 LILRA3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of LILRA3 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 LILRA3 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 LILRA3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of LILRA3 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 LILRA3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of LILRA3 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
ChEA Transcription Factor Targets | transcription factors binding the promoter of LILRA3 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 LILRA3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of LILRA3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing LILRA3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with LILRA3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of LILRA3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
COSMIC Cell Line Gene Mutation Profiles | cell lines with LILRA3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
CTD Gene-Chemical Interactions | chemicals interacting with LILRA3 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
DISEASES Experimental Gene-Disease Association Evidence Scores | diseases associated with LILRA3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset. | |
DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with LILRA3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
DisGeNET Gene-Disease Associations | diseases associated with LILRA3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
DisGeNET Gene-Phenotype Associations | phenotypes associated with LILRA3 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 LILRA3 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 LILRA3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
ENCODE Transcription Factor Targets | transcription factors binding the promoter of LILRA3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
GAD Gene-Disease Associations | diseases associated with LILRA3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
GAD High Level Gene-Disease Associations | diseases associated with LILRA3 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 LILRA3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
GeneRIF Biological Term Annotations | biological terms co-occuring with LILRA3 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 LILRA3 from the GeneSigDB Published Gene Signatures dataset. | |
GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of LILRA3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of LILRA3 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of LILRA3 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of LILRA3 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of LILRA3 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of LILRA3 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
GO Biological Process Annotations 2015 | biological processes involving LILRA3 gene from the curated GO Biological Process Annotations 2015 dataset. | |
GO Biological Process Annotations 2023 | biological processes involving LILRA3 gene from the curated GO Biological Process Annotations 2023 dataset. | |
GO Biological Process Annotations 2025 | biological processes involving LILRA3 gene from the curated GO Biological Process Annotations2025 dataset. | |
GO Cellular Component Annotations 2015 | cellular components containing LILRA3 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
GO Cellular Component Annotations 2023 | cellular components containing LILRA3 protein from the curated GO Cellular Component Annotations 2023 dataset. | |
GO Cellular Component Annotations 2025 | cellular components containing LILRA3 protein from the curated GO Cellular Component Annotations 2025 dataset. | |
GO Molecular Function Annotations 2015 | molecular functions performed by LILRA3 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
GO Molecular Function Annotations 2023 | molecular functions performed by LILRA3 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
GO Molecular Function Annotations 2025 | molecular functions performed by LILRA3 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
GTEx Tissue Gene Expression Profiles | tissues with high or low expression of LILRA3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of LILRA3 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of LILRA3 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
HPA Tissue Gene Expression Profiles | tissues with high or low expression of LILRA3 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of LILRA3 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
Hub Proteins Protein-Protein Interactions | interacting hub proteins for LILRA3 from the curated Hub Proteins Protein-Protein Interactions dataset. | |
HuGE Navigator Gene-Phenotype Associations | phenotypes associated with LILRA3 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
InterPro Predicted Protein Domain Annotations | protein domains predicted for LILRA3 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of LILRA3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of LILRA3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of LILRA3 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of LILRA3 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
LOCATE Curated Protein Localization Annotations | cellular components containing LILRA3 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset. | |
LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain LILRA3 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
MiRTarBase microRNA Targets | microRNAs targeting LILRA3 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset. | |
MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of LILRA3 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
MSigDB Cancer Gene Co-expression Modules | co-expressed genes for LILRA3 from the MSigDB Cancer Gene Co-expression Modules dataset. | |
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of LILRA3 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
Pathway Commons Protein-Protein Interactions | interacting proteins for LILRA3 from the Pathway Commons Protein-Protein Interactions dataset. | |
PFOCR Pathway Figure Associations 2024 | pathways involving LILRA3 protein from the Wikipathways PFOCR 2024 dataset. | |
Reactome Pathways 2024 | pathways involving LILRA3 protein from the Reactome Pathways 2024 dataset. | |
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of LILRA3 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of LILRA3 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of LILRA3 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of LILRA3 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of LILRA3 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of LILRA3 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with LILRA3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |