1. Gene Aliases

CD68, CD68 Molecule, CD68 Antigen, Macrosialin, SCARD1, GP110, LAMP4, Scavenger Receptor Class D, Member 1, Macrophage Antigen CD68, DKFZp686M18236, DKFZP686M18236, Gp110

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=CD68&keywords=CD68]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

autocrine signaling [Signaling between cells of the same type. The signal produced by the signaling cell binds to a receptor on, and affects a cell of the same type. GO:0035425]

cellular response to lipopolysaccharide [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. GO:0071222]

cellular response to nutrient levels [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus reflecting the presence, absence, or concentration of nutrients. GO:0031669]

cellular response to organic substance [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic substance stimulus. GO:0071310]

cellular response to oxidised low-density lipoprotein particle stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an oxidized lipoprotein particle stimulus. GO:0140052]

establishment of protein localization to organelle [The directed movement of a protein to a specific location on or in an organelle. Encompasses establishment of localization in the membrane or lumen of a membrane-bounded organelle. GO:0072594]

inflammatory response to antigenic stimulus [An inflammatory response to an antigenic stimulus, which can be include any number of T cell or B cell epitopes. GO:0002437]

negative regulation of dendritic cell antigen processing and presentation [Any process that stops, prevents, or reduces the frequency, rate, or extent of dendritic cell antigen processing and presentation. GO:0002605]

MSigDB Signatures:

REACTOME_NEUTROPHIL_DEGRANULATION: Neutrophil degranulation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NEUTROPHIL_DEGRANULATION.html]

REACTOME_INNATE_IMMUNE_SYSTEM: Innate Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INNATE_IMMUNE_SYSTEM.html]

KEGG_LYSOSOME: Lysosome [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_LYSOSOME.html]

WP_MACROPHAGE_MARKERS: Macrophage markers [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_MACROPHAGE_MARKERS.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes a 110-kD transmembrane glycoprotein that is highly expressed by human monocytes and tissue macrophages. It is a member of the lysosomal/endosomal-associated membrane glycoprotein (LAMP) family. The protein primarily localizes to lysosomes and endosomes with a smaller fraction circulating to the cell surface. It is a type I integral membrane protein with a heavily glycosylated extracellular domain and binds to tissue- and organ-specific lectins or selectins. The protein is also a member of the scavenger receptor family. Scavenger receptors typically function to clear cellular debris, promote phagocytosis, and mediate the recruitment and activation of macrophages. Alternative splicing results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]

GeneCards Summary: CD68 (CD68 Molecule) is a Protein Coding gene. Diseases associated with CD68 include Granular Cell Tumor and Histiocytic Sarcoma. Among its related pathways are Innate Immune System and LDL Oxidation in Atherogenesis. An important paralog of this gene is LAMP1.

UniProtKB/Swiss-Prot Summary: Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-specific lectins or selectins, allowing homing of macrophage subsets to particular sites. Rapid recirculation of CD68 from endosomes and lysosomes to the plasma membrane may allow macrophages to crawl over selectin-bearing substrates or other cells.

8. Cellular Location of Gene Product

Selective cytoplasmic expression in macrophages. Localized to the Golgi apparatus & vesicles. Predicted location: Membrane, Intracellular (different isoforms) [https://www.proteinatlas.org/ENSG00000129226/subcellular]

9. Mechanistic Information

Summary

CD68, a transmembrane glycoprotein highly expressed in monocytes and tissue macrophages, is involved in phagocytic activities and cell-pathogen interactions [CS: 10]. In the context of lung diseases and toxicities, CD68's dysregulation appears to be a response mechanism to counteract the damage caused by harmful stimuli [CS: 8]. For example, in response to cigarette smoke extract exposure, CD68 mRNA expression is elevated in lung tissue [CS: 9]. This upregulation likely serves to enhance the phagocytic capabilities of macrophages, facilitating the clearance of particulates and damaged cells induced by smoke [CS: 8]. This action reduces the potential for prolonged inflammation and tissue damage that can result from the accumulation of smoke particles [CS: 7].

Similarly, during influenza infection, CD68 expression is increased as part of the body's immune response [CS: 9]. CD68+ monocytic cells are recruited to the lung, mediating TLR4-dependent inflammation, a necessary response to control and eliminate the viral infection [CS: 8]. The upregulation of CD68 in this scenario likely aids in the efficient recruitment and activation of macrophages to the site of infection, enhancing the clearance of the virus and infected cells [CS: 8]. This mechanism, although contributing to inflammation, is crucial for controlling the spread of the virus and preventing further lung damage [CS: 9]. The increased expression of CD68 in these conditions reflects the body's attempt to mobilize an effective immune response to mitigate the impact of harmful agents on lung tissue [CS: 8].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: lung, lymphoid tissue (tissue enhanced) [https://www.proteinatlas.org/ENSG00000129226/tissue]

Cell type enchanced: hofbauer cells, kupffer cells, langerhans cells, macrophages, proximal enterocytes (cell type enhanced) [https://www.proteinatlas.org/ENSG00000129226/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: