CLEC7A (Dectin-1) is a type II transmembrane C-type lectin receptor (CLR) expressed primarily on [microglia](/cell-types/microglia) and other myeloid cells. Dectin-1 is the defining surface marker of disease-associated [microglia](/cell-types/microglia-neuroinflammation) (DAM) — a protective microglial activation state discovered in [Alzheimer's disease](/diseases/alzheimers-disease) that is dependent on [TREM2](/proteins/trem2-protein) signaling. CLEC7A activates SYK kinase-dependent phagocytic and inflammatory programs through its hemITAM signaling motif.
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CLEC7A / Dectin-1 Protein
Overview
CLEC7A (Dectin-1) is a type II transmembrane C-type lectin receptor (CLR) expressed primarily on [microglia](/cell-types/microglia) and other myeloid cells. Dectin-1 is the defining surface marker of disease-associated [microglia](/cell-types/microglia-neuroinflammation) (DAM) — a protective microglial activation state discovered in [Alzheimer's disease](/diseases/alzheimers-disease) that is dependent on [TREM2](/proteins/trem2-protein) signaling. CLEC7A activates SYK kinase-dependent phagocytic and inflammatory programs through its hemITAM signaling motif.
<div class="infobox infobox-protein"> [@brown2006] <div class="infobox-header">CLEC7A / Dectin-1 Protein</div> [@krasemann2017] <table> [@zhou2020] <tr><td class="infobox-label">Protein Name</td><td>C-type Lectin Domain Family 7 Member A (Dectin-1)</td></tr> [@safaiyan2021] <tr><td class="infobox-label">Gene</td><td>[CLEC7A](/genes/clec7a)</td></tr> [@goodridge2011] <tr><td class="infobox-label">UniProt ID</td><td>[Q9BXN2](https://www.uniprot.org/uniprot/Q9BXN2)</td></tr> [@deczkowska2018] <tr><td class="infobox-label">Molecular Weight</td><td>~28 kDa</td></tr> [@shah2021] <tr><td class="infobox-label">Subcellular Localization</td><td>Plasma membrane (type II orientation)</td></tr> <tr><td class="infobox-label">Protein Family</td><td>C-type lectin receptors (CLRs), Group V NK cell receptors</td></tr> <tr><td class="infobox-label">Associated Diseases</td><td>[Alzheimer's disease](/diseases/alzheimers-disease), [Multiple Sclerosis](/diseases/multiple-sclerosis), [ALS](/diseases/amyotrophic-lateral-sclerosis)</td></tr> </table> </div>
Structure
CLEC7A is a 247 amino acid type II transmembrane glycoprotein:
Domain Architecture
Cytoplasmic tail (aa 1–44): Contains a hemITAM motif (YxxxL) at Tyr-15 that recruits [SYK](/genes/syk) kinase upon phosphorylation. Unlike classical ITAM motifs (which have two YxxL sequences), the hemITAM is sufficient for SYK recruitment through receptor dimerization
Transmembrane domain (aa 45–66): Single-pass type II orientation (N-terminus intracellular, C-terminus extracellular)
Stalk region (aa 67–117): Flexible linker; contains an N-linked glycosylation site. The stalk enables dimerization, which is required for full signaling capacity
C-type lectin-like domain (CTLD) (aa 118–247): Binds beta-1,3-glucan ligands. Despite being classified as a C-type lectin, Dectin-1 binds ligands in a calcium-independent manner. The CTLD adopts a compact fold with two alpha-helices, two antiparallel beta-sheets, and a ligand-binding groove
Oligomerization
Dectin-1 forms homodimers on the cell surface through its stalk region and CTLD. Dimerization brings two hemITAM motifs into proximity, enabling productive SYK recruitment (SYK has tandem SH2 domains that bridge two phospho-hemITAMs).
Splice Variants
Two major isoforms exist:
Isoform A (full-length): Contains the stalk region; forms higher-order oligomers
Isoform B (Δ stalk): Lacks the stalk; remains monomeric but retains ligand binding and some signaling capacity
Normal Function
Pattern Recognition
In the periphery, Dectin-1 is the primary receptor for beta-1,3-glucans on fungal cell walls, mediating antifungal innate immunity. In the CNS, Dectin-1 recognizes endogenous ligands:
Damage-associated molecular patterns (DAMPs): Released from dying [neurons](/entities/neurons), including oxidized lipids and carbohydrates
Myelin debris: During demyelination, exposed carbohydrate structures on damaged myelin are recognized by Dectin-1
Amyloid-associated lipids: Modified lipoproteins in the plaque microenvironment
Signaling Cascade
Ligand binding triggers:
Src family kinase phosphorylation of the hemITAM Tyr-15
[SYK](/genes/syk) kinase recruitment and activation
CLEC7A is one of the most robustly upregulated genes in DAM:
Single-cell RNA-seq of 5xFAD mouse brains identified CLEC7A as a top Stage 2 DAM marker
CLEC7A+ microglia form a physical barrier around amyloid plaques, compacting them and limiting neuritic dystrophy
[TREM2](/genes/trem2) loss-of-function (e.g., R47H variant) prevents CLEC7A upregulation, locking microglia in a dysfunctional intermediate state
Human AD brain single-nucleus RNA-seq confirms CLEC7A as a conserved DAM marker
CLEC7A expression correlates with Braak stage and plaque density
Multiple Sclerosis
Dectin-1 has dual roles in demyelinating disease:
Protective: Promotes myelin debris phagocytosis, enabling remyelination by [oligodendrocyte precursors](/cell-types/oligodendrocyte-precursor-cells)
Pathogenic: Excessive Dectin-1 signaling can amplify inflammatory demyelination through IL-17 and GM-CSF production
ALS and Aging
CLEC7A marks activated microglia in the spinal cord of [SOD1](/genes/sod1) mice and in aging white matter (white matter-associated microglia, WAM). These populations share the DAM transcriptional signature.
Therapeutic Targeting
Beta-Glucan Agonists
Systemic administration of particulate beta-glucan (curdlan, whole glucan particles) in AD mouse models enhances amyloid phagocytosis and improves cognition
[TREM2](/proteins/trem2) agonist antibodies (AL002/latozinemab) in AD clinical trials promote CLEC7A upregulation by facilitating the Stage 1 → Stage 2 DAM transition.
[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)
[Unknown, Brown GD., Dectin-1: a signalling non-TLR pattern-recognition receptor (2006) (2006)](https://doi.org/10.1038/nri1745)
[Krasemann et al., The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia (2017) (2017)](https://doi.org/10.1016/j.immuni.2017.08.008)
[Zhou et al., Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and independent cellular responses in Alzheimer's disease (2020) (2020)](https://doi.org/10.1038/s41591-019-0695-9)
[Safaiyan et al., White matter aging drives microglial diversity (2021) (2021)](https://doi.org/10.1016/j.neuron.2021.01.027)
[Goodridge et al., Activation of the innate immune receptor Dectin-1 upon formation of a phagocytic synapse (2011) (2011)](https://doi.org/10.1038/nature10071)
[Deczkowska et al., Disease-associated microglia: a universal hypothesis for neurodegeneration (2018) (2018)](https://doi.org/10.1016/j.neuron.2018.09.030)
[Shah et al., Beta-glucan activates microglia and enhances amyloid clearance (2021) (2021)](https://doi.org/10.1186/s12974-021-02323-2)