OLR1

Summary

OLR1 (oxidized low density lipoprotein receptor 1, HGNC:8133) is a protein-coding gene on chromosome 12p13.2, encoding Oxidized low-density lipoprotein receptor 1 (P78380). Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells.

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.

Source: NCBI Gene 4973 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 42 total
• Druggable target: yes
• MANE Select transcript: NM_002543

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8133
Approved symbol	OLR1
Name	oxidized low density lipoprotein receptor 1
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	LOX-1, SCARE1, CLEC8A
Ensembl gene	ENSG00000173391
Ensembl biotype	protein_coding
OMIM	602601
Entrez	4973

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000309539, ENST00000339968, ENST00000432556, ENST00000536989, ENST00000538745, ENST00000538873, ENST00000539518, ENST00000543414, ENST00000543993, ENST00000544577, ENST00000545927, ENST00000896632

RefSeq mRNA: 3 — MANE Select: NM_002543 NM_001172632, NM_001172633, NM_002543

CCDS: CCDS53745, CCDS53746, CCDS8618

Canonical transcript exons

ENST00000309539 — 6 exons

Exon	Start	End
ENSE00001209326	10160786	10160925
ENSE00002273116	10172002	10172132
ENSE00002284894	10158301	10160021
ENSE00003620745	10169074	10169175
ENSE00003690051	10166712	10166957
ENSE00003785553	10160347	10160462

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 93.03.

FANTOM5 (CAGE): breadth broad, TPM avg 28.2621 / max 2902.8765, expressed in 514 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129496	26.4205	486
129492	1.5425	145
129494	0.1270	66
129495	0.1152	62
129493	0.0568	33

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	93.03	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.97	gold quality
bone marrow cell	CL:0002092	91.96	gold quality
upper lobe of left lung	UBERON:0008952	91.29	gold quality
spinal cord	UBERON:0002240	91.19	gold quality
upper lobe of lung	UBERON:0008948	90.67	gold quality
bone marrow	UBERON:0002371	90.31	gold quality
lower lobe of lung	UBERON:0008949	88.19	gold quality
placenta	UBERON:0001987	86.42	gold quality
lung	UBERON:0002048	86.37	gold quality
corpus callosum	UBERON:0002336	80.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.23	gold quality
vermiform appendix	UBERON:0001154	79.00	gold quality
gall bladder	UBERON:0002110	76.92	gold quality
substantia nigra	UBERON:0002038	75.98	gold quality
buccal mucosa cell	CL:0002336	75.43	gold quality
inferior vagus X ganglion	UBERON:0005363	75.19	gold quality
caudate nucleus	UBERON:0001873	75.13	gold quality
midbrain	UBERON:0001891	74.28	gold quality
prefrontal cortex	UBERON:0000451	74.20	gold quality
amygdala	UBERON:0001876	73.32	gold quality
caecum	UBERON:0001153	72.64	gold quality
middle frontal gyrus	UBERON:0002702	72.52	gold quality
hypothalamus	UBERON:0001898	72.30	gold quality
monocyte	CL:0000576	71.80	gold quality
trabecular bone tissue	UBERON:0002483	71.72	gold quality
putamen	UBERON:0001874	71.53	gold quality
mononuclear cell	CL:0000842	71.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.23	gold quality
tibial nerve	UBERON:0001323	70.88	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	6576.95
E-HCAD-15	yes	1123.78
E-MTAB-6819	yes	331.06
E-MTAB-6701	yes	127.70
E-CURD-122	yes	74.16
E-GEOD-84465	yes	42.54
E-GEOD-130148	yes	23.77
E-MTAB-9801	yes	6.44
E-MTAB-7303	no	14.16
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, HR, JUN, NFKB1, NFKB, POU2F1, PPARA, PPARG, RELA

miRNA regulators (miRDB)

98 targeting OLR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-8082	99.95	67.27	1170

Literature-anchored findings (GeneRIF, showing 40)

• LOX-1 gene expression is regulated through the cyclic AMP signaling pathway and histamine up-regulates LOX-1 expression via the H2 receptor in THP-1 monocytes (PMID:11728449)
• mediates the action of oxidized LDL that induces the decrease in NO release and the increased expression of adhesion molecules, which are typical changes in endothelial dysfunction (PMID:11915516)
• The expression of this receptor activates a variety of intracellular processes that lead to expression of adhesion molecules and endothelial activation. May be relevant in intra-arterial thrombogenesis and myocardial reperfusion injury. (PMID:11985903)
• oxidized LDL receptor expressed in vascular endothelial cells (PMID:12073608)
• LOX-1 is extensively expressed in the proliferated intima of grafted veins and in advanced atherosclerotic carotid arteries. Further, LOX-1 is colocalized with apoptotic cells. (PMID:12232563)
• Scavenger receptors are the main heat-shock-protein binding structures on human dendritic cells and LOX-1 is one of these molecules. (PMID:12354387)
• genetic variation in the OLR1 gene may modify the risk of AD in an APOE*4-dependent fashion (PMID:12384789)
• Results suggest Ox-LDL may be an important factor involved in the regulation of Fas-induced apoptosis via Ox-LDL/LOX-1 interaction in vascular endothelial cells. (PMID:12419941)
• Ox-LDL through its receptor LOX-1 triggers the CD40/CD40L signaling pathway that activates the inflammatory reaction in HCAECs. (PMID:12637341)
• oxidized high-density lipoprotein activates NF-kappa B via binding to oxidized low-density lipoprotein receptor-1 on the cell surface, followed by enhancement of intracellular reactive oxygen species production in endothelial cells (PMID:12646204)
• Data suggest that genetic variation in the OLR1 gene may modify the risk of Alzheimer’s disease. (PMID:12807963)
• a role for LOX-1 as mediator of the stimulatory effect of high glucose on monocyte adhesion (PMID:12829655)
• The oxidised LDL receptor 1 is a susceptibility gene for acute myocardial infarction. (PMID:14684693)
• High glucose concentrations enhance LOX-1 expression in human monocyte-derived macrophages & this is associated with foam cell formation. MDMs of patients with type 2 diabetes overexpress LOX-1 supporting its involvement in diabetic atherosclerosis. (PMID:15001526)
• CRP increased, through LOX-1, both human monocyte adhesion to aortic endothelial cells and oxLDL uptake by these cells. (PMID:15472120)
• the experimental evidence has suggested that LOX-1 may contribute to the development of hypertensive organ damage–REVIEW (PMID:15480893)
• Ox-LDL, mediated by LOX-1, enhanced MMP-3 production in articular chondrocytes. Increased ox-LDL with elevated of LOX-1 in rheumatoid arthritis(RA) cartilage indicates specific role of receptor-ligand interaction in cartilage pathology in RA. (PMID:15529384)
• LOX-1 gene variants at 501 found to be inversely associated with the severity of coronary artery disease (PMID:15562935)
• Data suggest a binding mode for the recognition of modified low density lipoprotein and other Lox-1 ligands based on the arrangement of critical binding residues on the Lox-1 structure. (PMID:15695803)
• The lectin-like oxidized low-density lipoprotein receptor (LOX-1), a recently identified receptor that plays a role in the uptake of oxidized low-density lipoproteins into endothelial cells, has a pivotal role in the pathogenesis of atherosclerosis. (PMID:15727724)
• Induction of LOX-1-related oxidation pathways and increased susceptibility to oxidative stress play a role in promoting vascular injury in old renal transplants independent of the recipient age. (PMID:15780115)
• angiotensin II upregulates LOX-1 and 12-LO and 15-LO expression in human vascular smooth muscle cells (PMID:15797645)
• LOX-1 and CD40 synergistically, but through a distinct pathway, work to induce endothelin-1 expression in endothelial cells. (PMID:15838273)
• Upregulation of LOX-1 by linoleic acid may contribute to endothelial dysfunction associated with type 2 diabetes (PMID:15855339)
• OLR1 polymorpism showed significant association with Alzheimer disease in Italian population. (PMID:15860461)
• The essential role of cytoplasmic sequence of LOX-1 for cell-surface sorting is established. (PMID:15935375)
• Serum LOX-1 appears to be a useful marker for early diagnosis of acute coronary syndromes. (PMID:16061745)
• Human LOX-1 recognizes phosphatidylserine, in a Ca2+-dependent manner, both in vitro and in cultured cells. (PMID:16146427)
• The critical role of Oct-1 in ox-LDL-induced LOX-1 promoter activation was further confirmed by mutagenesis assay (PMID:16173915)
• Expression of inflammatory molecules induced by oxidized low-density lipoproteins in HUVECs is mediated by LOX-1. (PMID:16188066)
• Ox-LDL and the specific receptor LOX-1 are involved in atherogenesis and atherothrombosis. LOX-1 downregulation is associated with the anti-platelet action of atorvastatin. 3’UTR/T LOX-1 polymorphism has been associated with increased risk of CAD. (PMID:16285995)
• Present data suggests that homozygosity for the C allele for OLR1+1073 polymorphism, selectively in individuals without APOE epsilon4 allele, may impair clearance of Abeta, and particularly Abeta40, from the brain across the blood-brain barrier. (PMID:16328515)
• LOX-1 mediates ox-LDL-induced SMC proliferation and plays a role in neointimal formation after vascular injury (PMID:16434026)
• Purification, crystallization and preliminary X-ray analysis of the ligand-binding domain of human lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1 (PMID:16511086)
• follicular atresia is not under the exclusive control of apoptosis and LOX-1-dependent autophagy represents an alternate form of programmed cell death (PMID:16690797)
• OLR1 gene single nucleotide polymorphism has little effect on an increased risk for ischemic cerebrovascular disease in the Japanese population. (PMID:17022953)
• These results indicate that the functional unit of LOX-1 is an oligomer and that oligomerization of LOX-1 is dependent on the receptor density on the plasma membrane. (PMID:17306253)
• the chimeric structural property of the NECK region may enable clustered LOX-1 on the cell surface to recognize OxLDL (PMID:17416594)
• role in platelet aggregation; expression on platelets increased 1.5- to 2.0-fold after ADP stimulation (PMID:17538005)
• small concentrations of oxLDL promote capillary tube formation by inducing the expression of VEGF via LOX-1-mediated activation of NADPH oxidase- MAPKs-NF-kappaB pathway. (PMID:17717293)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-193e13.5	ENSDARG00000052656
danio_rerio		ENSDARG00000074732
danio_rerio	si:dkey-26c10.5	ENSDARG00000088023
danio_rerio	si:ch211-170d8.8	ENSDARG00000090945
mus_musculus	Olr1	ENSMUSG00000030162
rattus_norvegicus	Olr1	ENSRNOG00000056219
drosophila_melanogaster	rgn	FBGN0261258
caenorhabditis_elegans		WBGENE00009156
caenorhabditis_elegans		WBGENE00013008

Paralogs (23): CLEC2D (ENSG00000069493), CD69 (ENSG00000110848), CLEC2B (ENSG00000110852), KLRB1 (ENSG00000111796), KLRD1 (ENSG00000134539), KLRC1 (ENSG00000134545), KLRG1 (ENSG00000139187), KLRF1 (ENSG00000150045), CLEC1A (ENSG00000150048), CLEC1B (ENSG00000165682), CLEC7A (ENSG00000172243), CLEC12A (ENSG00000172322), KLRC4 (ENSG00000183542), CLEC2A (ENSG00000188393), KLRG2 (ENSG00000188883), CLEC9A (ENSG00000197992), KLRC2 (ENSG00000205809), KLRC3 (ENSG00000205810), KLRK1 (ENSG00000213809), CLEC2L (ENSG00000236279), CLEC12B (ENSG00000256660), KLRF2 (ENSG00000256797), CLEC5A (ENSG00000258227)

Protein

Protein identifiers

Oxidized low-density lipoprotein receptor 1 — P78380 (reviewed: P78380)

Alternative names: C-type lectin domain family 8 member A, Lectin-like oxidized LDL receptor 1, Lectin-type oxidized LDL receptor 1

All UniProt accessions (8): B7ZAN8, P78380, F5GZH1, F5H001, F5H0N6, F5H3G7, F5H7N8, J3QTI8

UniProt curated annotations — full annotation on UniProt →

Function. 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. (Microbial infection) May serve as a receptor for adhesin A variant 3 (nadA) of N.meningitidis.

Subunit / interactions. Homodimer; disulfide-linked. May form a hexamer composed of 3 homodimers. Interacts with HSP70. (Microbial infection) Binds to the head and beginning of the coiled stalk of N.meningitidis adhesin A (nadA) variant 3; binding can be abrogated by monoclonal antibodies against the specific regions of NadA. Binding occurs in protein microarrays, in solution and when LOX-1 is expressed on the cell surface.

Subcellular location. Cell membrane. Membrane raft. Secreted.

Tissue specificity. Expressed at high level in endothelial cells and vascular-rich organs such as placenta, lung, liver and brain, aortic intima, bone marrow, spinal cord and substantia nigra. Also expressed at the surface of dendritic cells. Widely expressed at intermediate and low level.

Post-translational modifications. The intrachain disulfide-bonds prevent N-glycosylation at some sites. N-glycosylated.

Disease relevance. Independent association genetic studies have implicated OLR1 gene variants in myocardial infarction susceptibility. OLR1 may be involved in Alzheimer disease (AD). Involvement in AD is however unclear: according to some authors, variations in OLR1 modify the risk of AD. While according to others they do not.

Domain organisation. The cytoplasmic region is required for subcellular sorting on the cell surface. The C-type lectin domain mediates the recognition and binding of oxLDL.

Induction. By inflammatory cytokines such as TNF, IFNG/IFN-gamma, IL6/interleukin-6 and by pathological conditions such as hyperlipidemia, hypertension and diabetes mellitus. Up-regulated in atherosclerotic lesions, by oxLDL, reactive oxygen species and fluid shear stress, suggesting that it may participate in amplification of oxLDL-induced vascular dysfunction.

Isoforms (3)

UniProt ID	Names	Canonical?
P78380-1	1	yes
P78380-2	2
P78380-3	3

RefSeq proteins (3): NP_001166103, NP_001166104, NP_002534* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR033992	NKR-like_CTLD	Domain
IPR052332	OxLDL_rcpt1-like	Family

Pfam: PF00059

UniProt features (56 total): mutagenesis site 24, strand 8, disulfide bond 4, chain 2, lipid moiety-binding region 2, glycosylation site 2, splice variant 2, topological domain 2, helix 2, region of interest 2, sequence variant 1, transmembrane region 1, turn 1, domain 1, coiled-coil region 1, site 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
6TL7	X-RAY DIFFRACTION	1.11
7W5D	X-RAY DIFFRACTION	1.14
7XMP	X-RAY DIFFRACTION	1.27
1YPQ	X-RAY DIFFRACTION	1.4
1YXJ	X-RAY DIFFRACTION	1.78
7R8U	X-RAY DIFFRACTION	1.9
9IUD	X-RAY DIFFRACTION	1.98
1YPU	X-RAY DIFFRACTION	2.05
6TLA	X-RAY DIFFRACTION	2.16
3VLG	X-RAY DIFFRACTION	2.3
1YXK	X-RAY DIFFRACTION	2.4
6TL9	X-RAY DIFFRACTION	2.73
1YPO	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78380-F1	87.43	0.79

Antibody-complex structures (SAbDab): 1 — 7R8U

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 183 (not glycosylated)

Post-translational modifications (2): 36, 46

Disulfide bonds (4): 140, 144–155, 172–264, 243–256

Glycosylation sites (2): 73, 139

Mutagenesis-validated functional residues (24):

Position	Phenotype
22–25	impairs sorting into the cell surface but retains ability to bind oxldl. abolishes sorting into the cell surface; when a
70	abolishes sorting into the cell surface; when associated with 22-e–e-25.
140	abolishes homodimerization.
144	abolishes sorting into the cell surface and binding to acetylated ldl (acldl) while increasing n-glycosylation; when ass
150	abolishes binding to acetylated ldl (acldl), probably due to inappropriate homodimerization.
155	abolishes sorting into the cell surface and binding to acetylated ldl (acldl) while increasing n-glycosylation; when ass
172	abolishes sorting into the cell surface and binding to acetylated ldl (acldl) while increasing n-glycosylation; when ass
183	does not affect glycosylation state.
193	impairs binding to acetylated ldl (acldl); when associated with 198-aa-199.
198–199	impairs binding to acetylated ldl (acldl); when associated with l-193.
208	does not affect subcellular location but displays a strongly reduced affinity for acetylated ldl (acldl).
209–210	abolishes binding to acetylated ldl (acldl).
209	does not affect binding to acetylated ldl (acldl).
226	no effect.
226	abolishes binding to acetylated ldl (acldl); when associated with n-229 and n-231.
229	does not affect subcellular location but displays a reduced affinity for acetylated ldl (acldl). abolishes binding to ac
231	abolishes binding to acetylated ldl (acldl). abolishes binding to acldl; when associated with q-226 and n-229.
235–236	impairs binding to acetylated ldl (acldl); when associated with a-240.
240	impairs binding to acetylated ldl (acldl); when associated with 235-al-236.
243	abolishes sorting into the cell surface and binding to acetylated ldl (acldl) while increasing n-glycosylation; when ass
248	does not affect subcellular location but displays a reduced affinity for acetylated ldl (acldl).
256	abolishes sorting into the cell surface and binding to acetylated ldl (acldl) while increasing n-glycosylation; when ass
264	abolishes sorting into the cell surface and binding to acetylated ldl (acldl) while increasing n-glycosylation; when ass
267–273	impairs protein folding and transport.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 274 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, MODULE_172, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, AP1_01, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOCC_SECRETORY_GRANULE, MODULE_64, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_CELL_ADHESION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, ACCAATC_MIR509, AP1_Q4_01

GO Biological Process (8): immune system process (GO:0002376), proteolysis (GO:0006508), inflammatory response (GO:0006954), leukocyte cell-cell adhesion (GO:0007159), blood circulation (GO:0008015), lipoprotein metabolic process (GO:0042157), cell adhesion (GO:0007155), vesicle-mediated transport (GO:0016192)

GO Molecular Function (4): low-density lipoprotein particle receptor activity (GO:0005041), carbohydrate binding (GO:0030246), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), membrane (GO:0016020), specific granule membrane (GO:0035579), signaling receptor complex (GO:0043235), membrane raft (GO:0045121), tertiary granule membrane (GO:0070821)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Hemostasis	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein metabolic process	2
cellular process	2
binding	2
secretory granule membrane	2
biological_process	1
defense response	1
cell-cell adhesion	1
circulatory system process	1
transport	1
low-density lipoprotein particle binding	1
lipoprotein particle receptor activity	1
protein binding	1
nuclear lumen	1
membrane	1
cell periphery	1
specific granule	1
protein-containing complex	1
membrane microdomain	1
tertiary granule	1

Protein interactions and networks

STRING

1690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OLR1	HSPA4	P34932	980
OLR1	CRP	P02741	965
OLR1	SCARB1	Q8WTV0	855
OLR1	SCARB2	Q14108	851
OLR1	CD36	P16671	850
OLR1	LOX	P28300	746
OLR1	MSR1	P21757	713
OLR1	HSPD1	P10809	704
OLR1	LRP1	Q07954	678
OLR1	SCARF1	Q14162	664
OLR1	APOE	P02649	661
OLR1	ABCA1	O95477	651
OLR1	HSP90AA1	P07900	647
OLR1	STAB1	Q9NY15	646
OLR1	HSP90AB1	P08238	644

IntAct

21 interactions, top by confidence:

A	B	Type	Score
OLR1	OLR1	psi-mi:“MI:0195”(covalent binding)	0.710
OLR1	OLR1	psi-mi:“MI:0407”(direct interaction)	0.710
OLR1	OLR1	psi-mi:“MI:0914”(association)	0.710
OLR1	TCP1	psi-mi:“MI:0914”(association)	0.640
OLR1	TCP1	psi-mi:“MI:0915”(physical association)	0.640
TCP1	OLR1	psi-mi:“MI:0403”(colocalization)	0.640
TCP1	OLR1	psi-mi:“MI:0407”(direct interaction)	0.640
OLR1	F5	psi-mi:“MI:0915”(physical association)	0.590
OLR1	CCT4	psi-mi:“MI:0915”(physical association)	0.590
CCT4	OLR1	psi-mi:“MI:0407”(direct interaction)	0.590
OLR1	SLITRK4	psi-mi:“MI:0407”(direct interaction)	0.560
HSPA1L	OLR1	psi-mi:“MI:0915”(physical association)	0.400
EEA1	TCP1	psi-mi:“MI:0403”(colocalization)	0.270
M6PR	TCP1	psi-mi:“MI:0403”(colocalization)	0.270
HUNK	OLR1	psi-mi:“MI:0915”(physical association)	0.000
DSCR9	OLR1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): OLR1 (Reconstituted Complex), F5 (Affinity Capture-MS), OLR1 (Proximity Label-MS), OLR1 (Proximity Label-MS), OLR1 (Two-hybrid), SYVN1 (Affinity Capture-Western), OLR1 (Affinity Capture-Western), SYVN1 (Co-localization), F5 (Affinity Capture-MS), OLR1 (Affinity Capture-MS), OLR1 (Affinity Capture-MS), OLR1 (Affinity Capture-MS), OLR1 (Affinity Capture-MS), OLR1 (Affinity Capture-MS), OLR1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0E4BZH1, A4KWA1, D3W0D1, O35778, O54707, P27471, P27812, P27814, P78380, P79391, Q0VCS6, Q0ZUP0, Q0ZUP1, Q12918, Q13241, Q2HXU8, Q38HS3, Q49BZ4, Q58DF9, Q5NKN2, Q5NKN4, Q5QGZ9, Q60651, Q60652, Q60653, Q60660, Q60682, Q63378, Q64329, Q6QLQ4, Q6UVW9, Q80ZC8, Q863H3, Q8BWY2, Q8C567, Q8CJC7, Q8HZR8, Q8MHY9, Q8NC01, Q8VD98

Diamond homologs: C0HKZ6, D3W0D1, D3ZWT9, O70156, P02706, P07307, P08290, P0C7M8, P0C7M9, P10716, P20693, P23806, P27471, P27811, P27812, P27814, P34927, P49300, P49301, P70194, P78380, P79391, Q0H8B9, Q0ZCA7, Q0ZUP0, Q0ZUP1, Q13241, Q149M0, Q28768, Q3LUH2, Q49BZ4, Q5NKN2, Q5NKN4, Q60654, Q67EQ1, Q6QLQ4, Q6UXB4, Q6ZS10, Q7LZ71, Q80ZC8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

42 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

807 predictions. Top by Δscore:

Variant	Effect	Δscore
12:10160345:A:AC	donor_gain	1.0000
12:10160346:C:CC	donor_gain	1.0000
12:10160781:CTCA:C	donor_loss	1.0000
12:10160782:TCA:T	donor_loss	1.0000
12:10160783:CA:C	donor_loss	1.0000
12:10160784:A:AC	donor_gain	1.0000
12:10160785:C:CC	donor_gain	1.0000
12:10160921:AGGAG:A	acceptor_gain	1.0000
12:10160922:GGAG:G	acceptor_gain	1.0000
12:10160923:GAG:G	acceptor_gain	1.0000
12:10160923:GAGC:G	acceptor_loss	1.0000
12:10160925:GC:G	acceptor_loss	1.0000
12:10160926:C:CA	acceptor_loss	1.0000
12:10160926:C:CC	acceptor_gain	1.0000
12:10160927:T:A	acceptor_loss	1.0000
12:10164062:A:AC	donor_gain	1.0000
12:10166730:T:A	donor_gain	1.0000
12:10169072:A:AC	donor_gain	1.0000
12:10169073:C:CC	donor_gain	1.0000
12:10172007:G:C	donor_gain	1.0000
12:10160346:CAA:C	donor_gain	0.9900
12:10160346:CAAG:C	donor_gain	0.9900
12:10160778:ACACT:A	donor_loss	0.9900
12:10160779:CACTC:C	donor_loss	0.9900
12:10160780:ACTC:A	donor_loss	0.9900
12:10160785:CCAG:C	donor_gain	0.9900
12:10160924:AG:A	acceptor_gain	0.9900
12:10164063:T:C	donor_gain	0.9900
12:10166955:ATA:A	acceptor_gain	0.9900
12:10169073:CATTG:C	donor_gain	0.9900

AlphaMissense

1778 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:10160855:C:A	W165C	0.993
12:10160855:C:G	W165C	0.993
12:10160376:C:A	W217C	0.992
12:10160376:C:G	W217C	0.992
12:10160418:C:A	W203C	0.989
12:10160418:C:G	W203C	0.989
12:10160906:C:A	W148C	0.986
12:10160906:C:G	W148C	0.986
12:10160382:C:A	W215C	0.981
12:10160382:C:G	W215C	0.981
12:10159914:A:T	I263K	0.980
12:10159974:C:G	C243S	0.980
12:10159975:A:T	C243S	0.980
12:10159911:C:G	C264S	0.979
12:10159912:A:T	C264S	0.979
12:10159935:C:G	C256S	0.977
12:10159936:A:T	C256S	0.977
12:10160384:A:G	W215R	0.977
12:10160384:A:T	W215R	0.977
12:10160835:C:G	C172S	0.976
12:10160836:A:T	C172S	0.976
12:10160378:A:G	W217R	0.973
12:10160378:A:T	W217R	0.973
12:10160414:C:A	G205W	0.973
12:10160421:G:C	F202L	0.971
12:10160421:G:T	F202L	0.971
12:10160423:A:G	F202L	0.971
12:10160836:A:G	C172R	0.971
12:10159934:G:C	C256W	0.970
12:10159974:C:T	C243Y	0.969

dbSNP variants (sampled 300 via entrez): RS1000064997 (12:10165514 T>A,C), RS1000114217 (12:10171346 G>A), RS1000226288 (12:10162897 T>A,C), RS1000392931 (12:10168850 A>C), RS1000480327 (12:10168245 C>G), RS1000789153 (12:10168564 G>C), RS1001170734 (12:10171934 C>A,T), RS1001320835 (12:10177817 T>A), RS1001383332 (12:10177570 T>C), RS1001427988 (12:10177762 G>C), RS1001862107 (12:10167090 C>G,T), RS1001948462 (12:10161129 C>T), RS1002020855 (12:10161257 G>A,C), RS1002060920 (12:10167197 G>T), RS1002369477 (12:10173562 C>T)

Disease associations

OMIM: gene MIM:602601 | disease phenotypes: MIM:608446

GenCC curated gene-disease

Mondo (1): myocardial infarction, susceptibility to (MONDO:0012039)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3421522 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

86 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Tretinoin	increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
Resveratrol	decreases response to substance, decreases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Lipopolysaccharides	decreases reaction, increases expression, affects response to substance	2
Quercetin	increases expression, decreases reaction, affects cotreatment	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
Glupearl 19S	increases expression	1
4-oxoretinoic acid	increases expression	1
apocarotenal	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
titanium dioxide	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
2-tert-butylhydroquinone	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
andrographolide	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression	1
4-oxoretinol	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	increases expression	1
3-methylquercetin	decreases reaction, increases expression	1
demethoxycurcumin	decreases reaction, increases expression	1
acetovanillone	decreases reaction, increases expression	1
Am 580	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3424906	Binding	Inhibition of LOX1-induced DiI-L5 endocytosis in HAEC at 3 uM preincubated for 30 mins followed by DiI-L5 treatment measured after 8 hrs by fluorescence microscopic analysis	Sesamol reduces the atherogenicity of electronegative L5 LDL in vivo and in vitro. — J Nat Prod

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.