LY96 (Lymphocyte Antigen 96)
MD-2, the TLR4 co-receptor for LPS recognition and innate immune signaling
Gene Information Card
| Symbol | LY96 |
|---|---|
| Full Name | Lymphocyte Antigen 96 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q21.11 |
| NCBI Gene ID | 23643 ncbi.nlm.nih.gov/gene/23643 |
| Ensembl ID | ENSG00000154589 |
| UniProt ID | Q9Y6Y9 |
| OMIM ID | 605242 |
| HGNC ID | 17156 |
| Aliases | MD-2, ESOP-1, Ly-96 |
Description
The LY96 gene encodes the protein MD-2 (myeloid differentiation factor 2), a secreted glycoprotein that associates with Toll-like receptor 4 (TLR4) on the cell surface. MD-2 is essential for the recognition of lipopolysaccharide (LPS) from Gram-negative bacteria, forming the TLR4-MD-2 complex that initiates innate immune responses via NF-κB and MAPK pathways. LY96 is primarily expressed in immune cells and tissues exposed to microbial products.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sepsis / Endotoxin shock | Enhanced TLR4-MD-2 signaling in response to LPS leads to excessive cytokine release | PMID: 10653850, 11780160 |
| Atherosclerosis | MD-2 mediates inflammatory responses to modified lipoproteins and bacterial products in vascular endothelium | PMID: 19229032 |
| Asthma | Polymorphisms in LY96 associated with altered LPS responsiveness and airway inflammation | PMID: 15577926 |
| Inflammatory bowel disease | Dysregulated TLR4-MD-2 signaling contributes to chronic intestinal inflammation | PMID: 17210672 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Liver | 8.2 | Medium |
| Whole blood | 6.1 | Low |
| Bone marrow | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.3 | High expression; LPS-inducible |
| HEK293T | 0.8 | Low endogenous; used for TLR4 reconstitution |
| HUVEC | 4.2 | Moderate; upregulated by inflammatory stimuli |
| RAW 264.7 (mouse macrophage) | 18.1 | High; functional MD-2 |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.355G>A (p.Gly119Arg) | Missense | <0.01% | Reduced LPS binding and TLR4 activation |
| c.244C>T (p.Arg82Cys) | Missense | <0.01% | Impaired MD-2 secretion and complex formation |
| c.162_163insC | Frameshift | Rare | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations that impair MD-2 secretion, LPS binding, or TLR4 complex formation reduce innate immune signaling.
Gain of Function (GOF)
Not well documented; no common gain-of-function variants reported in LY96.
Dominant Negative (DN)
Some missense variants may act dominant-negatively by sequestering TLR4 in non-functional complexes.
View complete mutation data：
Gene Ontology (GO)
| • lipopolysaccharide binding (GO:0001530) | • receptor activity (GO:0004872) |
| • signal transduction (GO:0007165) | • Toll-like receptor 4 binding (GO:0035662) |
| • innate immune response (GO:0045087) | • plasma membrane (GO:0005886) |
Pathways
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• MyD88-independent TLR4 signaling (Reactome: R-HSA-166166)
• NF-kB activation by TLR4 (Reactome: R-HSA-975871)
Protein Summary
MD-2 (encoded by LY96) is a 160-amino-acid secreted glycoprotein that forms a heterodimer with the extracellular domain of TLR4. It contains a hydrophobic pocket that directly binds the lipid A moiety of LPS, enabling TLR4 dimerization and downstream signaling. MD-2 is critical for host defense against Gram-negative bacteria but also contributes to sterile inflammation and autoimmune pathology when dysregulated.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LY96 Knockout HEK293 Cell Line | EDJ-KQ3149 | Human | 23643 | Details Get a Quote |
| LY96 Knockout HeLa Cell Line | EDJ-KQ55789 | Human | 23643 | Details Get a Quote |
| LY96 Knockout A-549 Cell Line | EDJ-KQ64285 | Human | 23643 | Details Get a Quote |
| LY96 Knockout HCT 116 Cell Line | EDJ-KQ72732 | Human | 23643 | Details Get a Quote |
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