CLEC7A Gene

CLEC7A Gene

Overview

CLEC7A Gene

Overview

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

• 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

• 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

• [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

• [Amyloid-beta](/proteins/amyloid-beta) plaques and oligomers
• Dystrophic neurites surrounding plaques
• Myelin debris in demyelinating lesions
• Apoptotic neurons

Disease Associations

Alzheimer's Disease

• 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

Multiple Sclerosis

• 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

Aging

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

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

Considerations

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

Pathway Diagram

The following diagram shows the key molecular relationships involving CLEC7A Gene discovered through SciDEX knowledge graph analysis: