CLEC7A Gene
Overview
Mermaid diagram (expand to render)
CLEC7A (C-type Lectin Domain Family 7 Member A), also known as Dectin-1, is a pattern recognition receptor expressed primarily on [microglia](/cell-types/microglia) and other myeloid cells. CLEC7A has emerged as a key marker of disease-associated [microglia](/cell-types/microglia-neuroinflammation) (DAM), a microglial activation state identified in [Alzheimer's disease](/diseases/alzheimers-disease), [amyotrophic lateral sclerosis](/diseases/amyotrophic-lateral-sclerosis), and aging. CLEC7A functions downstream of [TREM2](/genes/trem2) signaling and is essential for the transition of microglia from homeostatic to neuroprotective phagocytic states.
<div class="infobox infobox-gene"> [@deczkowska2018]
<div class="infobox-header">CLEC7A</div> [@krasemann2017]
<table> [@brown2006]
<tr><td class="infobox-label">Full Name</td><td>C-type Lectin Domain Family 7 Member A (Dectin-1)</td></tr> [@safaiyan2021]
<tr><td class="infobox-label">Gene Symbol</td><td>CLEC7A</td></tr> [@shah2021]
<tr><td class="infobox-label">Chromosomal Location</td><td>12p13.2</td></tr> [@marschallinger2020]
<tr><td class="infobox-label">NCBI Gene ID</td><td>[64581](https://www.ncbi.nlm.nih.gov/gene/64581)</td></tr> [@zhou2020]
<tr><td class="infobox-label">OMIM</td><td>[606264](https://omim.org/entry/606264)</td></tr>
<tr><td class="infobox-label">Ensembl ID</td><td>[ENSG00000172243](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000172243)</td></tr>
<tr><td class="infobox-label">UniProt ID</td><td>[Q9BXN2](https://www.uniprot.org/uniprot/Q9BXN2)</td></tr>
<tr><td class="infobox-label">Protein</td><td>[CLEC7A / Dectin-1 Protein](/proteins/clec7a-protein)</td></tr>
<tr><td class="infobox-label">Associated Diseases</td><td>[Alzheimer's disease](/diseases/alzheimers-disease), [ALS](/diseases/amyotrophic-lateral-sclerosis), [Multiple Sclerosis](/diseases/multiple-sclerosis), [Parkinson's disease](/diseases/parkinsons-disease)</td></tr>
</table>
</div>
Function
CLEC7A encodes a type II transmembrane protein with an extracellular C-type lectin domain and an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like hemITAM. In the central nervous system, CLEC7A functions primarily in microglia:
Pattern Recognition
CLEC7A was originally characterized as a receptor for beta-1,3-glucans on fungal cell walls, mediating antifungal immunity. In the CNS, CLEC7A recognizes:
- Endogenous damage-associated molecular patterns (DAMPs) released from degenerating [neurons](/entities/neurons)
- Oxidized lipids and lipoproteins associated with [amyloid plaques](/mechanisms/amyloid-cascade)
- Myelin debris during demyelinating processes
- Apoptotic cell markers including exposed phosphatidylserine
Microglial Activation and DAM Transition
CLEC7A is one of the most robustly upregulated genes during the transition from homeostatic microglia to disease-associated microglia (DAM):
- Stage 1 DAM ([TREM2](/proteins/trem2)-independent): Downregulation of homeostatic genes ([CX3CR1](/genes/cx3cr1), [P2RY12](/genes/p2ry12), [TMEM119](/genes/tmem119)) and initial upregulation of [TYROBP/DAP12](/genes/tyrobp) and [APOE](/proteins/apoe)
- Stage 2 DAM (TREM2-dependent): Strong upregulation of CLEC7A, [CST7](/genes/cst7), [LPL](/genes/lpl), [SPP1](/genes/spp1), [ITGAX](/genes/itgax), and phagocytic genes. This transition requires [TREM2](/genes/trem2) signaling through [SYK](/genes/syk) kinase
Syk Kinase Signaling
Upon ligand binding, the hemITAM of CLEC7A is phosphorylated by Src family kinases, recruiting [SYK](/genes/syk) kinase. This activates downstream pathways:
- [NF-κB](/entities/nf-kb) ([NFKB1](/genes/nfkb1)) — pro-inflammatory cytokine production
- NFAT — gene transcription for immune activation
- PI3K/AKT ([PIK3CA](/genes/pik3ca), [AKT1](/genes/akt1)) — cell survival and phagocytosis
- CARD9/BCL10/MALT1 — inflammasome-independent cytokine production
- [ROS](/entities/reactive-oxygen-species) production via NADPH oxidase ([NOX2](/genes/nox2))
Phagocytosis
CLEC7A enhances microglial phagocytosis of:
- [Amyloid-beta](/proteins/amyloid-beta) plaques and oligomers
- Dystrophic neurites surrounding plaques
- Myelin debris in demyelinating lesions
- Apoptotic neurons
Disease Associations
Alzheimer's Disease
CLEC7A is among the most upregulated genes in plaque-associated microglia in AD:
- Single-cell RNA sequencing of microglia from [5xFAD](/mechanisms/5xfad-mouse-model) and human AD brains consistently identifies CLEC7A as a top DAM marker
- CLEC7A+ microglia cluster around amyloid plaques and form a barrier limiting plaque expansion
- [TREM2](/genes/trem2) loss-of-function variants (e.g., R47H) impair CLEC7A upregulation, preventing full DAM activation and worsening pathology
- CLEC7A expression correlates with Braak stage and amyloid burden in human AD brains
- Pharmacological activation of Dectin-1 with beta-glucan (curdlan) enhances microglial amyloid phagocytosis in AD mouse models
Amyotrophic Lateral Sclerosis
CLEC7A is upregulated in spinal cord microglia in the SOD1-G93A mouse model of [ALS](/diseases/amyotrophic-lateral-sclerosis). CLEC7A+ microglia accumulate around degenerating motor neurons and contribute to both neuroprotective debris clearance and neuroinflammatory damage.
Multiple Sclerosis
In [multiple sclerosis](/diseases/multiple-sclerosis) and experimental autoimmune encephalomyelitis (EAE):
- CLEC7A marks activated microglia in active demyelinating lesions
- Dectin-1 signaling promotes myelin debris phagocytosis, which is essential for remyelination
- However, excessive CLEC7A-mediated activation can exacerbate inflammatory demyelination
Parkinson's Disease
CLEC7A is upregulated in [substantia nigra](/brain-regions/substantia-nigra) microglia in PD. Single-nucleus RNA sequencing of PD brains reveals a DAM-like microglial population expressing high CLEC7A alongside [GPNMB](/genes/gpnmb) and [SPP1](/genes/spp1).
Aging
CLEC7A expression increases in aging microglia, even in the absence of overt pathology, suggesting it marks an age-related shift toward a more activated microglial state. White matter-associated microglia (WAM) in aged brains share the CLEC7A+/DAM signature.
Expression
CLEC7A expression in the healthy CNS is relatively low but increases dramatically in disease states:
- Microglia — primary CNS cell type expressing CLEC7A; expression is low in homeostatic microglia and high in DAM
- Perivascular macrophages — constitutive expression at the [blood-brain barrier](/entities/blood-brain-barrier)
- [Astrocytes](/entities/astrocytes) — minimal expression under basal conditions; some reactive [astrocytes](/cell-types/astrocytes) upregulate CLEC7A in AD
- Peripheral myeloid cells — high expression on monocytes, macrophages, dendritic cells, and neutrophils
Expression pattern via [Allen Brain Atlas](https://portal.brain-map.org/).
Therapeutic Targeting
Dectin-1 Agonists
- Beta-glucans (curdlan, zymosan, laminarin): Natural CLEC7A ligands that enhance microglial phagocytosis. Systemic beta-glucan administration in AD mouse models improves amyloid clearance and cognition
- Trained immunity: Beta-glucan-mediated epigenetic reprogramming of microglia may produce long-lasting neuroprotective effects through enhanced phagocytic capacity
TREM2 Pathway Modulation
Since CLEC7A upregulation depends on [TREM2](/genes/trem2) signaling, TREM2 agonist antibodies (AL002/latozinemab in clinical trials for AD) indirectly promote CLEC7A expression and DAM activation.
Considerations
The therapeutic window for CLEC7A modulation is nuanced — enhanced microglial phagocytosis is beneficial for clearing pathological aggregates, but excessive inflammatory activation may worsen neuronal damage. Context-dependent and temporally controlled approaches are under investigation.
External Links
- [NCBI Gene: CLEC7A](https://www.ncbi.nlm.nih.gov/gene/64581)
- [UniProt: Q9BXN2](https://www.uniprot.org/uniprot/Q9BXN2)
- [OMIM: 606264](https://omim.org/entry/606264)
- [GeneCards: CLEC7A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CLEC7A)
References
[Keren-Shaul et al., A unique microglia type associated with restricting development of Alzheimer's disease (2017) (2017)](https://doi.org/10.1016/j.cell.2017.05.018)
[Deczkowska et al., Disease-associated microglia: a universal hypothesis for the regulatory role of microglia in neurodegeneration (2018) (2018)](https://doi.org/10.1016/j.neuron.2018.09.030)
[Krasemann et al., The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases (2017) (2017)](https://doi.org/10.1016/j.immuni.2017.08.008)
[Unknown, Brown GD., Dectin-1: a signalling non-TLR pattern-recognition receptor (2006) (2006)](https://doi.org/10.1038/nri1745)
[Safaiyan et al., White matter aging drives microglial diversity (2021) (2021)](https://doi.org/10.1016/j.neuron.2021.01.027)
[Shah et al., Beta-glucan activates microglia and enhances amyloid clearance in Alzheimer's disease models (2021) (2021)](https://doi.org/10.1186/s12974-021-02323-2)
[Marschallinger et al., Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain (2020) (2020)](https://doi.org/10.1038/s41593-019-0566-1)
[Zhou et al., Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer's disease (2020) (2020)](https://doi.org/10.1038/s41591-019-0695-9)Pathway Diagram
The following diagram shows the key molecular relationships involving CLEC7A Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)