1. Gene Aliases

Oxidized Low Density Lipoprotein Receptor 1, CLEC8A, SCARE1, LOX-1, Oxidized Low-Density Lipoprotein Receptor 1, C-Type Lectin Domain Family 8 Member A, Lectin-Type Oxidized LDL Receptor 1, HLOX-1, LOX1, Oxidised Low Density Lipoprotein (Lectin-Like) Receptor 1, Oxidized Low Density Lipoprotein (Lectin-Like) Receptor 1, Oxidized Low-Density Lipoprotein Receptor 1 Soluble Form, Scavenger Receptor Class E Member 1, Lectin-Like Oxidized LDL Receptor 1, Lectin-Like OxLDL Receptor 1, Ox LDL Receptor 1, Ox-LDL Receptor 1, LOXIN, SLOX1

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=OLR1&keywords=Olr1]

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:

endocytosis [A vesicle-mediated transport process in which cells take up external materials or membrane constituents by the invagination of a part of the plasma membrane to form a new membrane-bounded vesicle. GO:0006897]

immune system process [Any process involved in the development or functioning of the immune system, an organismal system for calibrated responses to potential internal or invasive threats.|Note that this term is a direct child of 'biological_process ; GO:0008150' because some immune system processes are types of cellular process (GO:0009987), whereas others are types of multicellular organism process (GO:0032501). GO:0002376]

inflammatory response [The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. GO:0006954]

leukocyte cell-cell adhesion [The attachment of a leukocyte to another cell via adhesion molecules. GO:0007159]

lipoprotein metabolic process [The chemical reactions and pathways involving any conjugated, water-soluble protein in which the covalently attached nonprotein group consists of a lipid or lipids. GO:0042157]

negative regulation of gene expression [Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).|This term covers any process that negatively regulates the rate of production of a mature gene product, and so includes processes that negatively regulate that rate by reducing the level, stability or availability of intermediates in the process of gene expression. For example, it covers any process that reduces the level, stability or availability of mRNA or circRNA for translation and thereby reduces the rate of production of the encoded protein via translation. GO:0010629]

positive regulation of cellular process [Any process that activates or increases the frequency, rate or extent of a cellular process, any of those that are carried out at the cellular level, but are not necessarily restricted to a single cell. For example, cell communication occurs among more than one cell, but occurs at the cellular level. GO:0048522]

positive regulation of superoxide anion generation [Any process that activates or increases the frequency, rate or extent of enzymatic generation of superoxide by a cell. GO:0032930]

response to hydrogen peroxide [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrogen peroxide (H2O2) stimulus. GO:0042542]

vasoconstriction [A decrease in the diameter of blood vessels, especially arteries, due to constriction of smooth muscle cells that line the vessels, and usually causing an increase in blood pressure. GO:0042310]

MSigDB Signatures:

REACTOME_HEMOSTASIS: Hemostasis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_HEMOSTASIS.html]

CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_UP: Genes up-regulated in hepatoblastoma (HB) tumors as compared with non-tumor (NT) adjacent tissue. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_UP.html]

CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_HYPOMETHYLATED_AND_UP: Genes hypomethylated and overexpressed in hepatoblastoma (HB) tumors as compared with non-tumor (NT) adjacent tissue assessed by Infinium MethylationEPIC 850K array and Human Transcriptome Array 2.0 & RNA-sequencing. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_HYPOMETHYLATED_AND_UP.html]

KEGG_PPAR_SIGNALING_PATHWAY: PPAR signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PPAR_SIGNALING_PATHWAY.html]

WP_PPAR_SIGNALING_PATHWAY: PPAR signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PPAR_SIGNALING_PATHWAY.html]

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

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

ANDERSEN_CHOLANGIOCARCINOMA_CLASS2: Genes overexpressed in cholangiocarcinoma class 2 associated with poor prognosis. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ANDERSEN_CHOLANGIOCARCINOMA_CLASS2.html]

BENPORATH_CYCLING_GENES: Genes showing cell-cycle stage-specific expression [PMID: 12058064]. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BENPORATH_CYCLING_GENES.html]

WHITFIELD_CELL_CYCLE_G2_M: Genes periodically expressed in synchronized HeLa cells (cervical carcinoma), with peak during the G2/M phase of cell cycle. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WHITFIELD_CELL_CYCLE_G2_M.html]

JINESH_BLEBBISHIELD_TRANSFORMED_STEM_CELL_SPHERES_UP: Genes up-regulated in transformed spheres compared to blebbishields from RT4 cells [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/JINESH_BLEBBISHIELD_TRANSFORMED_STEM_CELL_SPHERES_UP.html]

REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL: Cell surface interactions at the vascular wall [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL.html]

CHICAS_RB1_TARGETS_CONFLUENT: Genes up-regulated in confluent IMR90 cells (fibroblast) after knockdown of RB1 [GeneID=5925] by RNAi. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CHICAS_RB1_TARGETS_CONFLUENT.html]

ZHANG_RESPONSE_TO_IKK_INHIBITOR_AND_TNF_UP: Genes up-regulated in BxPC3 cells (pancreatic cancer) after treatment with TNF [GeneID=7124] or IKI-1, an inhibitor of IkappaB kinase (IKK). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ZHANG_RESPONSE_TO_IKK_INHIBITOR_AND_TNF_UP.html]

ZWANG_CLASS_3_TRANSIENTLY_INDUCED_BY_EGF: Class III of genes transiently induced by EGF [GeneID =1950] in 184A1 cells (mammary epithelium). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ZWANG_CLASS_3_TRANSIENTLY_INDUCED_BY_EGF.html]

KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3: Genes with promoters occupied by SMAD2 or SMAD3 [GeneID=4087, 4088] in HaCaT cells (keratinocyte) according to a ChIP-chip analysis. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes a low density lipoprotein receptor that belongs to the C-type lectin superfamily. This gene is regulated through the cyclic AMP signaling pathway. The encoded protein binds, internalizes and degrades oxidized low-density lipoprotein. This protein may be involved in the regulation of Fas-induced apoptosis. This protein may play a role as a scavenger receptor. Mutations of this gene have been associated with atherosclerosis, risk of myocardial infarction, and may modify the risk of Alzheimer's disease. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2010]

GeneCards Summary: OLR1 (Oxidized Low Density Lipoprotein Receptor 1) is a Protein Coding gene. Diseases associated with OLR1 include Myocardial Infarction and Atherosclerosis Susceptibility. Among its related pathways are Innate Immune System and Response to elevated platelet cytosolic Ca2+. Gene Ontology (GO) annotations related to this gene include carbohydrate binding and low-density lipoprotein particle receptor activity. An important paralog of this gene is CLEC7A.

UniProtKB/Swiss-Prot Summary: Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that induces vascular endothelial cell activation and dysfunction, resulting in pro-inflammatory responses, pro-oxidative conditions and apoptosis. Its association with oxLDL induces the activation of NF-kappa-B through an increased production of intracellular reactive oxygen and a variety of pro-atherogenic cellular responses including a reduction of nitric oxide (NO) release, monocyte adhesion and apoptosis. In addition to binding oxLDL, it acts as a receptor for the HSP70 protein involved in antigen cross-presentation to naive T-cells in dendritic cells, thereby participating in cell-mediated antigen cross-presentation. Also involved in inflammatory process, by acting as a leukocyte-adhesion molecule at the vascular interface in endotoxin-induced inflammation. Also acts as a receptor for advanced glycation end (AGE) products, activated platelets, monocytes, apoptotic cells and both Gram-negative and Gram-positive bacteria. May serve as a receptor for adhesin A variant 3 (nadA) of N.meningitidis.

8. Cellular Location of Gene Product

Mainly localized to the nucleoplasm & plasma membrane. In addition localized to vesicles. Predicted location: Membrane, Intracellular (different isoforms) [https://www.proteinatlas.org/ENSG00000173391/subcellular]

9. Mechanistic Information

Summary

Olr1 encodes the LOX-1 receptor, which functions in the recognition and removal of oxidatively modified low-density lipoprotein (oxLDL) from the bloodstream, a process that counteracts oxidative damage and lipid accumulation in conditions like hyperglycemia [CS: 9]. Increased LOX-1 expression in response to high glucose and oxLDL presence may attempt to enhance clearance of harmful oxLDL, as well as participate in initiating an inflammatory response by activating NF-kappaB, potentially to recruit immune cells and repair damaged tissues in the liver [CS: 8]. However, overactivation of this receptor amplifies ROS production, driving a cycle of inflammation and oxidative stress that harms hepatocytes and contributes to the pathology of liver diseases, notably non-alcoholic fatty liver disease (NAFLD), where excessive lipid accumulation and inflammation are hallmarks [CS: 8].

However, in specific conditions of ER stress, such as those induced experimentally by tunicamycin, LOX-1 mRNA expression is downregulated potentially to prevent further uptake of modified lipoproteins that would exacerbate the stress on the ER [CS: 7].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: lung, placenta (tissue enhanced) [https://www.proteinatlas.org/ENSG00000173391/tissue]

Cell type enchanced: cytotrophoblasts, hofbauer cells, langerhans cells, macrophages, monocytes, syncytiotrophoblasts (group enriched) [https://www.proteinatlas.org/ENSG00000173391/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:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

No biomarkers associated with disease or organ of interest were found