CLEC7A (C-type Lectin Domain Family 7 Member A), also known as Dectin-1, is a pattern recognition receptor expressed primarily on microglia and other myeloid cells. CLEC7A has emerged as a key marker of disease-associated microglia (DAM), a microglial activation state identified in Alzheimer's disease, amyotrophic lateral sclerosis, and aging. CLEC7A functions downstream of TREM2 signaling and is essential for the transition of microglia from homeostatic to neuroprotective phagocytic states.
| Full Name | C-type Lectin Domain Family 7 Member A (Dectin-1) |
| Gene Symbol | CLEC7A |
| Chromosomal Location | 12p13.2 |
| NCBI Gene ID | [64581](https://www.ncbi.nlm.nih.gov/gene/64581) |
| OMIM | [606264](https://omim.org/entry/606264) |
| Ensembl ID | [ENSG00000172243](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000172243) |
| UniProt ID | [Q9BXN2](https://www.uniprot.org/uniprot/Q9BXN2) |
| Protein | [CLEC7A / Dectin-1 Protein](/proteins/clec7a-protein) |
| Associated Diseases | [Alzheimer's disease](/diseases/alzheimers-disease), [ALS](/diseases/amyotrophic-lateral-sclerosis), [Multiple Sclerosis](/diseases/multiple-sclerosis), [Parkinson's disease](/diseases/parkinsons-disease) |
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:
CLEC7A was originally characterized as a receptor for beta-1,3-glucans on fungal cell walls, mediating antifungal immunity. In the CNS, CLEC7A recognizes:
CLEC7A is one of the most robustly upregulated genes during the transition from homeostatic microglia to disease-associated microglia (DAM):
Upon ligand binding, the hemITAM of CLEC7A is phosphorylated by Src family kinases, recruiting SYK kinase. This activates downstream pathways:
CLEC7A enhances microglial phagocytosis of:
CLEC7A is among the most upregulated genes in plaque-associated microglia in AD:
CLEC7A is upregulated in spinal cord microglia in the SOD1-G93A mouse model of ALS. CLEC7A+ microglia accumulate around degenerating motor neurons and contribute to both neuroprotective debris clearance and neuroinflammatory damage.
In multiple sclerosis and experimental autoimmune encephalomyelitis (EAE):
CLEC7A is upregulated in substantia nigra microglia in PD. Single-nucleus RNA sequencing of PD brains reveals a DAM-like microglial population expressing high CLEC7A alongside GPNMB and SPP1.
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.
CLEC7A expression in the healthy CNS is relatively low but increases dramatically in disease states:
Expression pattern via Allen Brain Atlas.
Since CLEC7A upregulation depends on TREM2 signaling, TREM2 agonist antibodies (AL002/latozinemab in clinical trials for AD) indirectly promote CLEC7A expression and DAM activation.
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.