Details for: CLEC9A

Gene ID: 283420

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CLEC9A

Ensembl ID: ENSG00000197992

Description: C-type lectin domain containing 9A

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • myeloid leukocyte CL0000766
    CSI 5.08
    rCSI 4.69%
    PRS 99.8
  • hematopoietic stem cell CL0000037
    CSI 4.37
    rCSI 2.9%
    PRS 99.8
  • mononuclear phagocyte CL0000113
    CSI 2.78
    rCSI 6.13%
    PRS 99.87

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CLEC9A](/details-gene/283420) (C-type lectin domain containing 9A) encodes a type II transmembrane receptor that functions as a key sensor for cellular damage. As a member of the C-type lectin family, it specializes in recognizing and binding specific molecular patterns, particularly exposed actin filaments from necrotic cells ([Link](https://doi.org/10.1016/j.immuni.2012.03.009)). Its expression is highly restricted to specific subsets of the myeloid lineage. **Overall**, expression data reveals its highest significance in [myeloid leukocyte](/details-cell/CL0000766), [hematopoietic stem cell](/details-cell/CL0000037), and [mononuclear phagocyte](/details-cell/CL0000113) populations. This expression pattern aligns with its established role in initiating immune responses by facilitating the uptake and presentation of antigens from dead cells, particularly by a specialized subset of dendritic cells ([Link](https://doi.org/10.1074/jbc.m709923200)). ## Cellular Roles and Expression Landscape The expression profile of [CLEC9A](/details-gene/283420) underscores its specialized function within the hematopoietic system. The **Overall** context shows high significance scores in cells of the myeloid lineage, including [myeloid leukocyte](/details-cell/CL0000766) (CSI: 5.08) and [mononuclear phagocyte](/details-cell/CL0000113) (CSI: 2.78). This is consistent with published research identifying [CLEC9A](/details-gene/283420) as a marker for BDCA3+ (CD141+) dendritic cells and a small subset of monocytes ([Link](https://doi.org/10.1074/jbc.m709923200)). These cells are professional antigen-presenting cells renowned for their ability to cross-present antigens to CD8+ T cells, a critical step in initiating cytotoxic anti-tumor and anti-viral immunity. The notable significance in [hematopoietic stem cell](/details-cell/CL0000037) populations (CSI: 4.37) may suggest its early expression during myeloid differentiation pathways leading to these specialized dendritic cells. ## Pathways and Molecular Function Functionally, [CLEC9A](/details-gene/283420) is an integral [membrane](/details-cell/GO:0016020) protein located on the [cell surface](/details-cell/GO:0009986), where it performs [carbohydrate binding](/details-cell/GO:0030246) and other pattern recognition activities. Its primary biological role involves sensing cell death. Upon binding to components of necrotic cells, such as F-actin, [CLEC9A](/details-gene/283420) triggers [receptor-mediated endocytosis](/details-cell/GO:0006898), internalizing cellular debris for antigen processing ([Link](https://doi.org/10.1016/j.immuni.2012.03.009)). This process is directly linked to the [positive regulation of cytokine production](/details-cell/GO:0001819) and the subsequent activation and priming of T cells. By delivering antigens from damaged cells directly to the cross-presentation machinery, [CLEC9A](/details-gene/283420) serves as a critical bridge between innate recognition of tissue damage and the adaptive immune response. ## Research Directions The restricted expression and specialized function of [CLEC9A](/details-gene/283420) make it a focal point for immunological research and therapeutic development. Its role as a receptor for necrotic cell antigens has significant implications for both autoimmunity and anti-cancer immunity. Based on the available data, several testable hypotheses can be proposed: 1. Genetic polymorphisms in [CLEC9A](/details-gene/283420) that alter its binding affinity for F-actin could be associated with the risk or severity of autoimmune diseases characterized by high levels of cell death, such as systemic lupus erythematosus. 2. Targeting antigens to [CLEC9A](/details-gene/283420) on dendritic cells using antibody-antigen conjugates will be more effective at inducing cytotoxic T-cell responses against tumors than conventional vaccination strategies, as has been suggested in preclinical models ([Link](https://doi.org/10.1172/jci34584)). 3. The expression of [CLEC9A](/details-gene/283420) on tumor-infiltrating dendritic cells may serve as a prognostic biomarker, where higher expression correlates with improved T-cell infiltration and better patient outcomes in immunogenic tumors. To test the second hypothesis regarding its therapeutic utility, a key experiment could be designed. To directly assess the efficacy of [CLEC9A](/details-gene/283420) targeting in a therapeutic context, one could generate an antibody-drug conjugate (ADC) where a cytotoxic payload is linked to a [CLEC9A](/details-gene/283420)-specific antibody. This ADC could be tested in a co-culture system containing [CLEC9A](/details-gene/283420)-positive target cells (e.g., a transfected cell line) and bystander cells. The hypothesis predicts that the ADC will selectively kill only the [CLEC9A](/details-gene/283420)-expressing cells, demonstrating target-specific delivery and efficacy. Given its highly specific expression on a dendritic cell subset critical for initiating cytotoxic immunity, [CLEC9A](/details-gene/283420) represents an exceptional therapeutic target. The primary strategy would be activation or targeting, not inhibition. It is an ideal candidate for developing novel vaccine adjuvants, antibody-antigen conjugates for cancer immunotherapy ([Link](https://doi.org/10.1172/jci34584)), or as a target for CAR-T therapies designed to modulate dendritic cell function.

Genular Protein ID: 3529455332

Symbol: CLC9A_HUMAN

Name: C-type lectin domain family 9 member A

UniProtKB Accession Codes:

Q6UXN8 B0ZBM2

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 1 EvolutionaryTrace 1 GO 5 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 UniLectin 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 18408006

Title: CLEC9A is a novel activation C-type lectin-like receptor expressed on BDCA3+ dendritic cells and a subset of monocytes.

PubMed ID: 18408006

DOI: 10.1074/jbc.m709923200

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 18497879

Title: Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin.

PubMed ID: 18497879

DOI: 10.1172/jci34584

PubMed ID: 22483802

Title: The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments.

PubMed ID: 22483802

DOI: 10.1016/j.immuni.2012.03.009

Sequence Information:

  • Length: 241
  • Mass: 27324
  • Checksum: 6158B3AC44EEC9C3
  • Sequence:
    • MHEEEIYTSL QWDSPAPDTY QKCLSSNKCS GACCLVMVIS CVFCMGLLTA SIFLGVKLLQ 
VSTIAMQQQE KLIQQERALL NFTEWKRSCA LQMKYCQAFM QNSLSSAHNS SPCPNNWIQN 
RESCYYVSEI WSIWHTSQEN CLKEGSTLLQ IESKEEMDFI TGSLRKIKGS YDYWVGLSQD 
GHSGRWLWQD GSSPSPGLLP AERSQSANQV CGYVKSNSLL SSNCSTWKYF ICEKYALRSS 
V