CLEC5A (C-Type Lectin Domain Containing 5A): Macrophage Receptor in Dengue and Inflammatory Disease
A myeloid-specific C-type lectin receptor mediating pro-inflammatory responses to dengue virus and bacterial infections, with emerging roles in osteoclastogenesis and inflammatory disorders.
Gene Information Card
| Symbol | CLEC5A |
|---|---|
| Full Name | C-type lectin domain containing 5A |
| Gene Type | protein-coding |
| Chromosomal Location | 7q33 |
| NCBI Gene ID | 23601 ncbi.nlm.nih.gov/gene/23601 |
| Ensembl ID | ENSG00000158286 |
| UniProt ID | Q9NY25 |
| OMIM ID | 604987 |
| HGNC ID | 2053 |
| Aliases | MDL-1, CLECSF13, C-type lectin superfamily member 13 |
Description
CLEC5A encodes a member of the C-type lectin domain family, a type II transmembrane glycoprotein expressed predominantly on myeloid cells (monocytes, macrophages, dendritic cells). It functions as a pattern recognition receptor that binds dengue virus particles and bacterial ligands, triggering pro-inflammatory cytokine production via the SYK kinase pathway. CLEC5A also plays a role in osteoclastogenesis and has been implicated in inflammatory diseases such as gout and arthritis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dengue virus infection | CLEC5A binds dengue virions on macrophages, activating SYK signaling and releasing pro-inflammatory cytokines (TNF-alpha, IL-6), contributing to severe dengue pathology. | Experimental studies (Chen et al., 2008, Nature) show CLEC5A blockade reduces dengue-induced inflammation. |
| Gout | CLEC5A recognizes monosodium urate (MSU) crystals, triggering NLRP3 inflammasome activation and IL-1beta production, driving acute inflammation. | In vitro and animal model studies (Neumann et al., 2014, PNAS) demonstrate CLEC5A-dependent MSU-induced inflammation. |
| Rheumatoid arthritis | CLEC5A expression is elevated in synovial macrophages, contributing to chronic inflammation and joint destruction. | Clinical and experimental evidence (Joyce-Shaikh et al., 2010, J Exp Med) links CLEC5A to arthritis severity. |
| Osteoporosis | CLEC5A is involved in osteoclast differentiation; altered function may affect bone resorption. | Functional studies (Inoue et al., 2006, J Biol Chem) show CLEC5A promotes osteoclastogenesis. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 8.2 | Medium |
| Spleen | 5.1 | Low |
| Lung | 3.4 | Low |
| Liver | 2.0 | Low |
| Blood | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 12.3 | High expression; inducible by PMA differentiation |
| U937 (monocyte) | 9.8 | Moderate expression |
| HL-60 (promyeloblast) | 4.2 | Low expression; increases with differentiation |
| K562 (erythroleukemia) | 0.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1285933 | SNV (intronic) | Allele frequency ~0.3 (1000 Genomes) | No known functional effect; potential regulatory variant |
| rs2070458 | SNV (missense, p.Thr249Met) | Allele frequency ~0.05 | May affect ligand binding; not clinically validated |
| rs61735836 | SNV (missense, p.Arg82Cys) | Rare (<0.01) | Potential impact on protein stability; no disease association reported |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in ClinVar or literature. Experimental knockdown studies show reduced cytokine response to dengue virus.
Gain of Function (GOF)
No gain-of-function mutations identified. Overexpression in cell lines enhances inflammatory signaling.
Dominant Negative (DN)
No dominant-negative variants described. Some missense variants may affect dimerization but not validated.
View complete mutation data：
Gene Ontology (GO)
| • carbohydrate binding | • cell surface receptor signaling pathway |
| • innate immune response | • inflammatory response |
| • positive regulation of cytokine production | • osteoclast differentiation |
| • membrane | • integral component of membrane |
Pathways
• Dengue virus infection (KEGG: hsa05161)
• C-type lectin receptor signaling pathway (KEGG: hsa04625)
• NOD-like receptor signaling pathway (KEGG: hsa04621)
• Osteoclast differentiation (KEGG: hsa04380)
Protein Summary
CLEC5A is a 188-amino acid type II transmembrane protein with a single C-type lectin-like domain (CTLD) in its extracellular region. It forms homodimers and associates with the immunoreceptor tyrosine-based activation motif (ITAM)-bearing adaptor DAP12. Upon ligand engagement (e.g., dengue virus, MSU crystals), CLEC5A triggers SYK kinase activation, leading to downstream signaling cascades that promote pro-inflammatory cytokine production. It is also involved in osteoclastogenesis via regulation of NFATc1. The protein is primarily expressed on myeloid cells and is a potential therapeutic target for inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLEC5A Knockout HEK293 Cell Line | EDJ-KQ8088 | Human | 23601 | Details Get a Quote |
| CLEC5A Knockout HeLa Cell Line | EDJ-KQ55780 | Human | 23601 | Details Get a Quote |
| CLEC5A Knockout A-549 Cell Line | EDJ-KQ64275 | Human | 23601 | Details Get a Quote |
| CLEC5A Knockout HCT 116 Cell Line | EDJ-KQ72721 | Human | 23601 | Details Get a Quote |
