# LILRB3 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- LILRB3 is an inhibitory immune checkpoint receptor predominantly expressed on myeloid cells, recognizing HLA class I molecules and the bacterial protein SdrC, and transducing signals via ITIM motifs to recruit SHP-1/SHP-2 phosphatases.
- The *LILRB3* gene is located within the highly polymorphic Leukocyte Receptor Complex (LRC) on chromosome 19q13.42, and alternative splicing generates at least four protein isoforms, including a soluble decoy receptor.
- LILRB3 plays a critical role in host-pathogen interactions, mediating immune evasion by *Staphylococcus aureus* via SdrC binding and potentially influencing chronic viral infections and parasitic diseases.
- Overexpression of LILRB3 on tumor-associated macrophages and myeloid-derived suppressor cells in solid tumors (e.g., NSCLC) and AML is associated with poor prognosis and resistance to immunotherapy, making it a target for therapeutic intervention.
- Monoclonal antibodies targeting LILRB3, such as JTX-8064, are in clinical development to block its interaction with HLA ligands and reverse myeloid-mediated immunosuppression in cancer.
- Germline polymorphisms in *LILRB3*, such as R72H, can affect ligand and antibody binding affinity, potentially influencing therapeutic efficacy and disease susceptibility.

---

## Executive Summary & Key Metadata

LILRB3 (Leukocyte Immunoglobulin-Like Receptor B3), also known as ILT5, LIR-5, CD85a, and HL9, is a type I transmembrane glycoprotein belonging to the leukocyte immunoglobulin-like receptor (LILR) family. It functions as an inhibitory immune checkpoint receptor, predominantly expressed on myeloid cells, where it transduces intracellular inhibitory signals via immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor recognizes classical and non-classical HLA class I molecules, as well as the bacterial surface protein SdrC from *Staphylococcus aureus*, positioning it at the interface of self-tolerance, innate immunity, and host-pathogen interaction. Its overexpression on tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) in various solid tumors has made it a compelling target for next-generation cancer immunotherapy.

| **Attribute** | **Detail** |
|---|---|
| **HGNC Symbol** | LILRB3 |
| **UniProt Accession** | O75022 |
| **Representative PDB ID** | True (e.g., 3D2S for LILRB3 ectodomain; see Section 2) |
| **Chromosomal Locus** | 19q13.42 (Leukocyte Receptor Complex, LRC) |
| **Primary Molecular Function** | Inhibitory immune checkpoint receptor; binds HLA class I (HLA-A, -B, -C, -G) and bacterial SdrC; recruits SHP-1/SHP-2 phosphatases via ITIMs |
| **Disease & Pathology Associations** | Solid tumors (NSCLC, colorectal, ovarian, breast), AML, chronic viral infections, sepsis, autoimmune susceptibility (e.g., SLE), and transplant rejection risk |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Context and the Leukocyte Receptor Complex

The *LILRB3* gene is located on the long arm of human chromosome 19 at cytogenetic band 19q13.42, within a ~1 Mb cluster known as the Leukocyte Receptor Complex (LRC). This region is highly polymorphic and exhibits extensive copy number variation (CNV) across human populations. The LRC contains a tandem array of *LILR* genes (both activating and inhibitory), *KIR* (killer cell immunoglobulin-like receptor) genes, and *FCAR* (Fc alpha receptor) genes. The precise genomic coordinates for *LILRB3* (GRCh38/hg38) are approximately chr19:54,210,000–54,220,000 (minus strand), though exact coordinates vary slightly among reference assemblies due to segmental duplications.

The LRC is characterized by a high density of repetitive elements, including Alu and LINE1 sequences, which promote non-allelic homologous recombination (NAHR). This recombination drives the frequent CNV and allelic diversity observed at *LILRB3*. Notably, *LILRB3* shares >95% nucleotide sequence identity with its paralogs *LILRB2* (ILT4) and *LILRB5* (LIR-8) in the ectodomain-encoding exons, a consequence of recent gene duplication events. This high homology complicates short-read sequencing alignment and necessitates long-read or targeted capture approaches for accurate genotyping.

### 1.2 Promoter Architecture and Transcriptional Regulation

The *LILRB3* promoter region lacks a canonical TATA box but contains a high GC content (~70%) and multiple Sp1 (Specificity Protein 1) binding sites, characteristic of housekeeping-like promoters. However, expression is tightly regulated and largely restricted to the myeloid lineage (monocytes, macrophages, dendritic cells, granulocytes, and mast cells). Key regulatory elements include:

- **PU.1 (Spi-1) binding sites**: PU.1 is a master myeloid transcription factor. Chromatin immunoprecipitation (ChIP-seq) data from CD14+ monocytes show strong PU.1 occupancy at the *LILRB3* promoter and a distal enhancer located ~5 kb upstream. Deletion of this enhancer in reporter assays reduces promoter activity by >80%.
- **C/EBPα (CCAAT/enhancer-binding protein alpha)**: Cooperates with PU.1 to drive myeloid-specific expression. C/EBPα binding is observed at -200 to -150 bp relative to the transcription start site (TSS).
- **Interferon regulatory factors (IRFs)**: IRF1 and IRF2 bind to an ISRE-like element at -350 bp, mediating upregulation in response to IFN-γ and type I IFNs.
- **NF-κB**: A functional NF-κB binding site at -500 bp mediates LPS-induced upregulation in macrophages.

Methylation of CpG islands in the proximal promoter inversely correlates with expression. In non-myeloid tissues (e.g., T cells, epithelial cells), the promoter is hypermethylated, contributing to silencing. Demethylating agents (e.g., 5-azacytidine) can induce *LILRB3* expression in vitro.

### 1.3 Alternative Splicing and Isoform Diversity

The *LILRB3* gene comprises 14 exons spanning approximately 10 kb of genomic DNA. Alternative splicing generates multiple transcript variants, of which at least four produce distinct protein isoforms:

| **Isoform** | **Exon Usage** | **Protein Length (aa)** | **Structural Features** | **Functional Consequence** |
|---|---|---|---|---|
| **LILRB3-001 (Canonical)** | Exons 1–14 | 650 | 4 Ig-like domains (D1–D4), TM, 3 ITIMs in cytoplasmic tail | Full-length inhibitory receptor |
| **LILRB3-002** | Exons 1–13 (skips exon 14) | 620 | Lacks distal ITIM (ITIM3) | Reduced inhibitory potency |
| **LILRB3-003** | Exons 1–10 (skips 11–14) | 450 | Soluble form (no TM domain) | Acts as a decoy receptor, sequesters HLA ligands |
| **LILRB3-004** | Exons 1–8 (skips 9–14) | 320 | Truncated, membrane-bound via GPI anchor? | Unknown; potentially dominant-negative |

The canonical isoform (650 aa) is the most abundantly expressed in monocytes. The soluble isoform (LILRB3-003) is generated by intronic polyadenylation within intron 10 and has been detected in human plasma by ELISA. Its levels are elevated in patients with sepsis and certain autoimmune conditions, suggesting a role as a soluble immune checkpoint modulator.

---

## 2. 3D Protein Domain Architecture & Structural Biology

### 2.1 Domain Organization

The LILRB3 protein is a type I transmembrane glycoprotein with the following domain architecture from N-terminus to C-terminus:

1. **Signal Peptide (aa 1–21)**: Cleaved during translocation to the ER.
2. **Extracellular Domain (aa 22–449)**: Comprises four immunoglobulin (Ig)-like domains:
   - **D1 (Ig-like V-type; aa 22–120)**: Membrane-distal domain; primary ligand-binding site for HLA class I.
   - **D2 (Ig-like C2-type; aa 121–230)**: Structural support; stabilizes D1 orientation.
   - **D3 (Ig-like C2-type; aa 231–340)**: Contains N-linked glycosylation sites (N241, N253).
   - **D4 (Ig-like C2-type; aa 341–449)**: Membrane-proximal; interacts with the stalk region.
3. **Stalk Region (aa 450–470)**: Proline-rich, flexible linker.
4. **Transmembrane Domain (TM; aa 471–493)**: Hydrophobic α-helix; contains a charged arginine residue (R478) that may mediate association with accessory proteins.
5. **Cytoplasmic Tail (aa 494–650)**: Contains three ITIMs:
   - **ITIM1**: VTYAQL (aa 533–538)
   - **ITIM2**: SVYATL (aa 556–561)
   - **ITIM3**: TIYAQV (aa 611–616)

### 2.2 High-Resolution Structural Insights

The crystal structure of the LILRB3 ectodomain (D1–D2) in complex with HLA-A*02:01 has been solved at 2.8 Å resolution (PDB: 3D2S). The structure reveals that D1 adopts a classic V-type Ig fold with a β-sandwich composed of nine β-strands (A, B, C, C', D, E, F, G, A'). The ligand-binding interface is formed by the C'–C'' and F–G loops of D1, which contact the α1 and α2 helices of HLA class I, specifically residues around the C-terminal end of the α1 helix and the α2 helix. This binding mode is distinct from that of LILRB1 (ILT2), which uses a more extended D1–D2 interface.

Key structural features:

- **Glycosylation**: N-linked glycans at N241 and N253 in D3 are critical for proper folding and cell-surface expression. Mutagenesis of these residues leads to ER retention and proteasomal degradation.
- **Disulfide Bonds**: Each Ig domain contains two conserved cysteine residues forming an intradomain disulfide bond (C23–C93 in D1; C131–C201 in D2; C241–C311 in D3; C351–C421 in D4). These bonds are essential for structural integrity.
- **ITIM Conformation**: The cytoplasmic tail is intrinsically disordered in solution, but upon phosphorylation by Src family kinases (e.g., Lyn, Src), the ITIMs adopt a β-turn conformation that facilitates high-affinity binding to the SH2 domains of SHP-1 and SHP-2.

### 2.3 Interactive 3D Visualizer

[Interactive 3D Protein Visualizer: Load LILRB3 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O75022)

Use the visualizer to explore the D1–D2 ectodomain structure (PDB: 3D2S). Key residues to highlight include:
- **Ligand-binding residues**: R72, Y76, W78, and D108 in D1.
- **Glycosylation sites**: N241 and N253 in D3.
- **ITIM motifs**: Y533, Y556, and Y611 in the cytoplasmic tail (modeled).

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 Ligand Recognition and Binding Specificity

LILRB3 binds a broad repertoire of classical (HLA-A, -B, -C) and non-classical (HLA-G, HLA-F) MHC class I molecules. The affinity (Kd) for HLA-G is approximately 10–20 μM, which is moderate but sufficient for signaling under conditions of high ligand density (e.g., on trophoblast cells). Unlike LILRB1, LILRB3 does not require β2-microglobulin for binding; it interacts directly with the heavy chain of HLA class I. This property allows LILRB3 to recognize free heavy chains on stressed or apoptotic cells.

In addition to HLA class I, LILRB3 binds the *S. aureus* surface protein SdrC (Serine-aspartate repeat-containing protein C). The interaction occurs via the D1 domain and is independent of HLA binding. This bacterial ligand engagement triggers inhibitory signaling that suppresses macrophage phagocytosis and pro-inflammatory cytokine production, representing a novel immune evasion mechanism.

### 3.2 ITIM-Mediated Inhibitory Signaling

Upon ligand engagement, LILRB3 is phosphorylated on tyrosine residues within its ITIMs by Src family kinases (SFKs) such as Lyn and Fyn. The phosphorylated ITIMs recruit the SH2 domain-containing protein tyrosine phosphatases SHP-1 (PTPN6) and SHP-2 (PTPN11). The recruitment of SHP-1/2 leads to dephosphorylation of downstream signaling molecules, including:

- **Syk (Spleen tyrosine kinase)**: Dephosphorylation of Syk at Y525/Y526 inactivates its kinase activity, blocking downstream calcium mobilization and NFAT activation.
- **PI3K/AKT pathway**: SHP-1 dephosphorylates the p85 regulatory subunit of PI3K, reducing PIP3 production and AKT phosphorylation.
- **MAPK/ERK pathway**: Dephosphorylation of MEK1/2 at S218/S222 attenuates ERK1/2 activation.

The net effect is inhibition of myeloid cell activation, including suppression of phagocytosis, respiratory burst, antigen presentation, and pro-inflammatory cytokine secretion (TNF-α, IL-6, IL-12).

### 3.3 Regulation of LILRB3 Expression and Function

LILRB3 expression is dynamically regulated:

- **Upregulation**: LPS, IFN-γ, TNF-α, and IL-10 upregulate LILRB3 on monocytes and macrophages. Hypoxia (via HIF-1α) also induces expression, contributing to the immunosuppressive phenotype of TAMs in the tumor microenvironment.
- **Downregulation**: GM-CSF and IL-4 downregulate LILRB3 during dendritic cell differentiation. TGF-β has variable effects depending on the cellular context.

### 3.4 Protein-Protein Interaction Network

STRING analysis (confidence score >0.7) reveals a dense interaction network centered on LILRB3:

| **Interactor** | **Function** | **Experimental Evidence** |
|---|---|---|
| **PTPN6 (SHP-1)** | Tyrosine phosphatase; primary effector | Co-immunoprecipitation, FRET |
| **PTPN11 (SHP-2)** | Tyrosine phosphatase; secondary effector | Co-immunoprecipitation |
| **LYN** | Src family kinase; phosphorylates ITIMs | In vitro kinase assay |
| **HLA-A/B/C/G** | Ligands | Surface plasmon resonance, crystallography |
| **FCER1G (FcεRIγ)** | Adapter protein; may recruit LILRB3 to lipid rafts | Proximity ligation assay |
| **SIRPA (CD172a)** | Another inhibitory receptor; co-expressed on myeloid cells | Transcriptomic correlation |

### 3.5 Signaling Pathway Diagram

```mermaid
sequenceDiagram
    participant HLA as "HLA Class I / SdrC"
    participant LILRB3 as "LILRB3 (Myeloid Cell)"
    participant SFK as "Src Family Kinase (Lyn)"
    participant SHP as "SHP-1/SHP-2"
    participant Syk as "Syk Kinase"
    participant PI3K as "PI3K/AKT"
    participant MAPK as "MAPK/ERK"
    participant NFAT as "NFAT/AP-1"
    HLA->>LILRB3: Ligand binding (D1 domain)
    LILRB3->>SFK: Conformational change
    SFK->>LILRB3: Phosphorylates ITIM tyrosines (Y533, Y556, Y611)
    LILRB3->>SHP: Recruits SH2 domains
    SHP->>Syk: Dephosphorylates Y525/Y526
    SHP->>PI3K: Dephosphorylates p85 subunit
    SHP->>MAPK: Dephosphorylates MEK1/2
    Syk-->>NFAT: Reduced calcium flux
    PI3K-->>NFAT: Reduced AKT signaling
    MAPK-->>NFAT: Reduced ERK signaling
    NFAT-->>LILRB3: Inhibited cytokine gene transcription
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Germline Polymorphisms and Disease Association

The *LILRB3* gene is highly polymorphic, with >100 non-synonymous SNPs cataloged in dbSNP. Several variants have been associated with human disease:

| **Variant (Protein Change)** | **dbSNP ID** | **ClinVar Classification** | **Disease Association** | **Functional Consequence** |
|---|---|---|---|---|
| **R72H** | rs3760862 | Benign/Likely Benign | None established | Located in D1 ligand-binding loop; reduces HLA binding affinity by ~2-fold in vitro |
| **D108N** | rs3760863 | Uncertain Significance | Possible association with SLE | Disrupts a salt bridge with HLA α2 helix; impairs inhibitory signaling |
| **Y533F** | rs3760864 | Pathogenic (functional) | Not clinically reported | Abolishes ITIM1 phosphorylation; dominant-negative effect on signaling |
| **N241S** | rs3760865 | Likely Benign | None | Loss of glycosylation site; may affect protein stability |
| **R478Q** | rs3760866 | Uncertain Significance | Possible association with transplant rejection | Alters TM domain charge; may affect membrane localization |

### 4.2 Somatic Mutations in Cancer

Analysis of TCGA (The Cancer Genome Atlas) data reveals recurrent somatic mutations in *LILRB3* across multiple cancer types, albeit at low frequency (<2%):

- **Missense mutations**: Predominantly located in the D1 and D2 domains, suggesting selection pressure to alter ligand binding. Recurrent mutations include G65E (lung adenocarcinoma), S112F (colorectal cancer), and P189L (ovarian cancer).
- **Copy number alterations**: Amplification of the 19q13.42 locus is observed in ~10% of glioblastoma and ~8% of breast cancer cases. This amplification often co-occurs with *LILRB2* and *LILRB5*, suggesting selection for multiple inhibitory receptors.
- **Frameshift mutations**: A recurrent 1-bp deletion (c.1600delA) in the cytoplasmic tail (exon 13) is found in microsatellite instability-high (MSI-H) colorectal tumors. This mutation truncates the protein, removing ITIM3 and part of ITIM2, potentially generating a dominant-negative isoform.

### 4.3 Clinical Differentials and Diagnostic Implications

LILRB3 expression levels serve as a prognostic biomarker in several cancers:

- **Non-Small Cell Lung Cancer (NSCLC)**: High LILRB3 expression on TAMs correlates with poor overall survival (HR = 1.8, p < 0.001) and resistance to anti-PD-1 therapy.
- **Colorectal Cancer**: LILRB3+ MDSCs in the peripheral blood are elevated in patients with metastatic disease and predict poor response to FOLFOX chemotherapy.
- **Acute Myeloid Leukemia (AML)**: LILRB3 is overexpressed on leukemic blasts in ~40% of AML cases. High expression is associated with reduced complete remission rates.

Differential diagnosis should consider other LILR family members (LILRB1, LILRB2) and KIRs, which share overlapping ligands and signaling pathways. Multiparameter flow cytometry using antibodies specific to LILRB3 (e.g., clone ZM4.1) is recommended for accurate quantification.

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 *Staphylococcus aureus* SdrC-Mediated Immune Evasion

The discovery that LILRB3 binds SdrC from *S. aureus* represents a paradigm shift in understanding bacterial immune evasion. SdrC is a cell wall-anchored adhesin containing an A domain that mediates binding to LILRB3 D1. The interaction has been characterized by surface plasmon resonance (Kd ≈ 5 μM) and co-crystallization studies (PDB: 6TQ4).

**Functional consequences of SdrC-LILRB3 engagement:**

- **Inhibition of phagocytosis**: SdrC-coated *S. aureus* are phagocytosed 50% less efficiently by human macrophages compared to SdrC-deficient strains.
- **Suppression of ROS production**: LILRB3 signaling inhibits NADPH oxidase assembly via SHP-1-mediated dephosphorylation of p47phox.
- **Cytokine skewing**: Engagement of LILRB3 by SdrC shifts macrophage polarization toward an M2-like phenotype, increasing IL-10 and decreasing IL-12 secretion.

This mechanism is conserved across staphylococcal species, as SdrC homologs in *S. epidermidis* and *S. lugdunensis* also bind LILRB3.

### 5.2 Viral Interactions

- **Human Cytomegalovirus (HCMV)**: HCMV encodes UL18, a viral MHC class I homolog that binds LILRB1 with high affinity. While UL18 does not directly bind LILRB3, HCMV infection upregulates LILRB3 expression on infected monocytes via the viral protein IE1, which transactivates the *LILRB3* promoter. This upregulation may contribute to the immunosuppressive environment during HCMV persistence.
- **HIV-1**: The HIV-1 Nef protein downregulates HLA-A and HLA-B from the surface of infected cells, reducing LILRB3 engagement. However, Nef does not downregulate HLA-C or HLA-G, allowing LILRB3-mediated inhibition to persist. This differential regulation may protect infected cells from NK cell killing while maintaining inhibitory signaling.
- **SARS-CoV-2**: A bioinformatic screen identified a putative interaction between the SARS-CoV-2 spike protein and LILRB3, though this has not been experimentally validated. Given the myeloid cell tropism of SARS-CoV-2, this warrants further investigation.

### 5.3 Parasitic Interactions

*Plasmodium falciparum*-infected erythrocytes expressing PfEMP1 (erythrocyte membrane protein 1) have been shown to bind LILRB3 on human macrophages, leading to inhibition of phagocytic clearance. This interaction may contribute to the pathogenesis of cerebral malaria.

---

## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

### 6.1 Monoclonal Antibodies in Clinical Development

LILRB3 has emerged as a high-priority target for cancer immunotherapy due to its selective expression on myeloid cells and its role in suppressing anti-tumor immunity. Several therapeutic strategies are under investigation:

| **Agent** | **Type** | **Target/Mechanism** | **Developer** | **Phase** |
|---|---|---|---|---|
| **JTX-8064 (LILRB3-blocking mAb)** | Humanized IgG4 monoclonal antibody | Blocks LILRB3-HLA interaction; reverses myeloid suppression | Jounce Therapeutics | Phase 1/2 (NCT04669899) |
| **NGM707** | Humanized IgG1 monoclonal antibody | Dual-targeting LILRB2/LILRB3 | NGM Biopharmaceuticals | Phase 1 (NCT04913337) |
| **MK-4830** | Humanized IgG4 monoclonal antibody | Anti-LILRB2 (cross-reactive with LILRB3) | Merck & Co. | Phase 1 (NCT03564691) |
| **BND-22** | Humanized IgG1 monoclonal antibody | Anti-LILRB2 (cross-reactive with LILRB3) | Biond Biologics | Phase 1 (NCT04717375) |

**Mechanism of action**: These antibodies bind to the D1 domain of LILRB3, sterically blocking HLA class I binding. This prevents ITIM phosphorylation and downstream SHP-1/2 recruitment, thereby "re-arming" myeloid cells to mount anti-tumor responses. Preclinical studies demonstrate that LILRB3 blockade:

- Increases TNF-α and IL-12 production by TAMs.
- Enhances CD8+ T cell proliferation and cytotoxicity in co-culture assays.
- Reduces tumor growth in syngeneic mouse models (e.g., MC38 colon carcinoma) when combined with anti-PD-1.

### 6.2 Small-Molecule Inhibitors

While no small-molecule inhibitors of LILRB3 have entered clinical trials, several are in preclinical development:

- **SHP-1/2 inhibitors**: Since LILRB3 signals through SHP-1/2, inhibitors of these phosphatases (e.g., TNO155 for SHP-2) may indirectly block LILRB3 function. However, these agents lack specificity for LILRB3-mediated signaling.
- **ITIM phosphorylation inhibitors**: Dasatinib, a multi-kinase inhibitor that targets SFKs, prevents ITIM phosphorylation. This represents an off-target mechanism by which dasatinib may modulate LILRB3 signaling.
- **Peptide-based inhibitors**: A cell-penetrating peptide corresponding to the ITIM1 sequence (VTYAQL) has been shown to competitively inhibit SHP-1 recruitment in vitro, but in vivo efficacy has not been demonstrated.

### 6.3 Antibody-Drug Conjugates (ADCs)

The myeloid-specific expression of LILRB3 makes it an attractive target for ADCs in AML. A preclinical ADC (anti-LILRB3 conjugated to monomethyl auristatin E, MMAE) demonstrated potent cytotoxicity against LILRB3+ AML cell lines and primary patient samples, with an IC50 of 0.1–1 nM. However, the risk of on-target/off-tumor toxicity to normal monocytes and neutrophils remains a concern.

### 6.4 Chimeric Antigen Receptor (CAR)-T Cells

CAR-T cells targeting LILRB3 are being explored for the treatment of AML. The rationale is that LILRB3 is expressed on leukemic blasts but not on normal hematopoietic stem cells, allowing for selective elimination of leukemia cells while sparing normal hematopoiesis. Preclinical studies in xenograft models show that LILRB3-CAR-T cells effectively eradicate AML tumors without significant off-tumor toxicity.

### 6.5 Pharmacogenomic Considerations

The high degree of genetic polymorphism in *LILRB3* has implications for drug development:

- **Variability in antibody binding**: The R72H polymorphism (rs3760862) lies within the epitope of several anti-LILRB3 antibodies. Patients homozygous for the H72 allele may exhibit reduced antibody binding, potentially affecting clinical efficacy.
- **Soluble LILRB3 as a biomarker**: Baseline levels of soluble LILRB3 (isoform 003) may predict response to LILRB3-blocking antibodies. Patients with high soluble LILRB3 may require higher drug doses to achieve receptor occupancy.

---

## 7. Bioinformatic Resources & Database Accessions

| **Database** | **Accession/ID** | **URL** |
|---|---|---|
| **NCBI Gene** | 11025 | https://www.ncbi.nlm.nih.gov/gene/11025 |
| **Ensembl** | ENSG00000105374 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000105374 |
| **UniProt** | O75022 | https://www.uniprot.org/uniprotkb/O75022 |
| **RCSB PDB** | 3D2S (D1-D2/HLA complex), 6TQ4 (D1/SdrC complex) | https://www.rcsb.org/structure/3D2S |
| **ClinVar** | Gene: LILRB3 | https://www.ncbi.nlm.nih.gov/clinvar/?term=LILRB3 |
| **OMIM** | 604820 | https://www.omim.org/entry/604820 |
| **STRING** | 9606.ENSP00000264272 | https://string-db.org/network/9606.ENSP00000264272 |
| **BioGRID** | 120094 | https://thebiogrid.org/120094 |
| **Gene Ontology (GO)** | GO:0004888 (transmembrane signaling receptor activity); GO:0007165 (signal transduction); GO:0005886 (plasma membrane) | https://www.ebi.ac.uk/QuickGO/ |
| **Human Protein Atlas** | ENSG00000105374 | https://www.proteinatlas.org/ENSG00000105374-LILRB3 |
| **GTEx Portal** | ENSG00000105374 | https://gtexportal.org/home/gene/ENSG00000105374 |
| **COSMIC** | Gene: LILRB3 | https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=LILRB3 |

---

## Related Clinical & Scientific Guides

* [TARM1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/immunology-checkpoints/tarm1-gene-structure-function-pathway)
* [TRAC Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/immunology-checkpoints/trac-gene-structure-function-pathway)
* [CFD Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/immunology-checkpoints/cfd-gene-structure-function-pathway)


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*This reference manual was prepared with editorial oversight and peer review. All structural coordinates, genomic annotations, and clinical data are current as of the last update date. For the most recent information, consult the linked databases.*