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7 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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OR6A2
olfactory receptor family 6 subfamily A member 2
Chromosome 11 · 11p15.4
NCBI Gene: 8590Ensembl: ENSG00000184933.6HGNC: HGNC:15301UniProt: A0A126GW91
10PubMed Papers
12Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membraneolfactory receptor activitydetection of chemical stimulus involved in sensory perception of smellmembranemetabolic syndromeepididymitispsoriasisovarian dysfunction
✦AI Summary

OR6A2 is a human olfactory receptor and G protein-coupled receptor that detects medium-chain aldehydes, particularly octanal, through a reversible Schiff base linkage mechanism 1. Beyond its canonical role in odorant detection, OR6A2 has critical extranasal functions in vascular inflammation and immune regulation. In vascular macrophages, OR6A2 activation by octanal—a lipid peroxidation product present in blood plasma at pathologically relevant concentrations—triggers NLRP3 inflammasome assembly and interleukin-1β secretion 2. This mechanism drives atherosclerosis development; notably, OR6A2 expression is upregulated in monocytes from patients with large abdominal aortic aneurysms (AAAs) 3. OR6A2 also regulates monocyte recruitment via CX3CR1-dependent migration, with genetic deletion or pharmacological antagonism protecting against AAA formation 3. During myocardial ischemia-reperfusion injury, elevated OR6A2 expression correlates with increased major adverse cardiovascular events and activates the Olfr2/cAMP/PKA/NR4A1 axis, promoting mitochondrial fission and oxidative stress in macrophages 4. IL-1R1/TLR signaling potentiates OR6A2-mediated inflammasome activation by inhibiting β-arrestin-2-mediated receptor internalization 5. These findings establish OR6A2 as a promising therapeutic target for cardiovascular inflammatory diseases.

Sources cited
1
OR6A2 detects octanal and activates NLRP3 inflammasome to drive atherosclerosis in vascular macrophages
PMID: 35025664
2
OR6A2 is expressed in macrophages and triggers inflammasome assembly and IL-1β secretion upon octanal binding
PMID: 36311776
3
OR6A2 is upregulated in monocytes from AAA patients; regulates monocyte recruitment via CX3CR1 and protects against AAA when deleted
PMID: 41473953
4
IL-1R1/TLR signaling potentiates OR6A2-mediated NLRP3 inflammasome activation by blocking β-arrestin-2-mediated receptor endocytosis
PMID: 41343277
5
OR6A2 is the human ortholog of Olfr2 and represents a therapeutic target for atherosclerosis
PMID: 35283015
6
Elevated OR6A2 expression associates with major adverse cardiovascular events and activates the Olfr2/cAMP/PKA/NR4A1 axis during myocardial IR injury
PMID: 41223038
7
OR6A2 senses medium-chain aldehydes through reversible Schiff base linkage with K4.60 and belongs to a cilantro-perception-associated OR cluster
PMID: 41570822
Disease Associationsⓘ12
metabolic syndromeOpen Targets
0.07Suggestive
epididymitisOpen Targets
0.03Suggestive
ovarian dysfunctionOpen Targets
0.03Suggestive
psoriasisOpen Targets
0.03Suggestive
orchitisOpen Targets
0.03Suggestive
placental retentionOpen Targets
0.02Suggestive
achalasia-alacrima syndromeOpen Targets
0.01Suggestive
atherosclerosisOpen Targets
0.01Suggestive
neuroblastomaOpen Targets
0.00Suggestive
severe malarial anemiaOpen Targets
0.00Suggestive
Aarskog-Scott syndrome, X-linkedOpen Targets
0.00Suggestive
aneurysmOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
OR8U9Shared pathway100%OR8U8Shared pathway100%OR14J1Shared pathway100%OR9K2Shared pathway100%OR5B3Shared pathway100%OR5K4Shared pathway100%
Tissue Expression6 tissues
Heart
0%
Lung
0%
Bone Marrow
0%
Ovary
0%
Liver
0%
Brain
0%
Gene Interaction Network
Click a node to explore
OR6A2OR8U9OR8U8OR14J1OR9K2OR5B3OR5K4
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O95222
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.95LoF Tolerant
pLIⓘ
0.08Tolerant
Observed/Expected LoF0.51 [0.29–0.95]
RankingsWhere OR6A2 stands among ~20K protein-coding genes
  • #17,131of 20,598
    Most Researched10
  • #8,924of 17,882
    Most Constrained (LOEUF)0.95
Genes detectedOR6A2
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production.
PMID: 35025664
Science · 2022
1.00
2
Olfactory receptors in macrophages and inflammation.
PMID: 36311776
Front Immunol · 2022
0.86
3
Olfr2 Promotes Recruitment of Monocytes via CX3CR1 in Abdominal Aortic Aneurysm.
PMID: 41473953
Circ Res · 2026
0.71
4
Interleukin-1/Toll-like receptor signaling potentiates macrophage olfactory receptor 2-driven atherosclerosis.
PMID: 41343277
Cell Rep · 2025
0.57
5
Odorant receptors in macrophages: potential targets for atherosclerosis.
PMID: 35283015
Trends Immunol · 2022
0.43