CLEC12A

Official Full Name

C-type lectin domain family 12 member A

Organism

Homo sapiens

GeneID

160364

Background

This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signaling, glycoprotein turnover, and roles in inflammation and immune response. The protein encoded by this gene is a negative regulator of granulocyte and monocyte function. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. This gene is closely linked to other CTL/CTLD superfamily members in the natural killer gene complex region on chromosome 12p13. [provided by RefSeq, May 2011]

Synonyms

CLL1; MICL; CD371; CLL-1; DCAL-2; hKLRL1;

Protein Sequence

MSEEVTYADLQFQNSSEMEKIPEIGKFGEKAPPAPSHVWRPAALFLTLLCLLLLIGLGVLASMFHVTLKIEMKKMNKLQNISEELQRNISLQLMSNMNISNKIRNLSTTLQTIATKLCRELYSKEQEHKCKPCPRRWIWHKDSCYFLSDDVQTWQESKMACAAQNASLLKINNKNALEFIKSQSRSYDYWLGLSPEEDSTRGMRVDNIINSSAWVIRNAPDLNNMYCGYINRLYVQYYHCTYKKRMICEKMANPVQLGSTYFREA

Open

Disease

Acute myeloid leukaemia, BCR-ABL1-negative chronic myeloid leukaemia, Leukaemia, Lymphoma, Multiple myeloma

Approved Drug

Clinical Trial Drug

9 +

Discontinued Drug

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Tag	Price

Cat.No.	Product Name	Price

Detailed Information

Within the C-type lectin (CTL) group is CLEC12A (C-type lectin domain family 12 member A). Members of this family often have similar ways of folding proteins. They play important roles in various biological functions, such as helping cells stick together, communicating between cells, processing glycoproteins, and responding to inflammation and immune reactions. With its translated protein directing neutrophil and monocyte activity, the CLEC12A gene is found in the 12p13 region of human chromosome 12 close to the natural killer gene complex. The protein made by CLEC12A has a special part that can recognize certain sugars and help manage how cells communicate.

Structure and Function of CLEC12A

CLEC12A is a type II transmembrane glycoprotein that has an outside part called a C-type lectin-like domain and a section that spans the membrane. Six important cysteine residues in its protein structure help keep the protein folded correctly in the C-type lectin family. The YXXM motif and the ITIM in CLEC12A help it associate with proteins called SHP-1 and SHP-2. This contact happens through a process called phosphorylation, which lowers cell stimulation reactions.

Research shows that CLEC12A helps control the immune system, which affects how our body responds to infections and inflammation. Clec12A might work with uric acid crystals to lower inflammation caused by cell death. CLEC12A is thought to help move dendritic cells into the brain by crossing the blood-brain barrier, and it could help treat various illnesses.

Figure 1 illustrates the signal transduction pathways potentially regulated by CLEC12A, highlighting receptors it influences in neutrophils and indicating signaling molecules possibly inhibited by CLEC12A, with specific emphasis on its effects on TNF receptor activation and other pathways in myeloid cells. Figure 1. Signal transduction pathways are potentially regulated by CLEC12A. (McLeish KR, et al., 2023)

Expression Characteristics of CLEC12A

CLEC12A is found in normal blood stem cells and their early forms. It becomes more active as these cells grow into myeloid cells, especially in mature forms like granulocytes and monocytes. CLEC12A is mainly found in mature myeloid cells such as granulocytes, macrophages, monocytes, and dendritic cells, according to a flow cytometry study. It is not present in normal B cells, T cells, red blood cells, or megakaryocytes. CLEC12A is found mainly in specific cell types, which means it has less impact on regular cells. This makes it an ideal tumor marker.

Application of CLEC12A in Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is a very aggressive blood cancer that has a poor outlook and is hard to treat. Research on CLEC12A in acute myeloid leukemia (AML) shows it may be useful for tracking leftover cancer cells, diagnosing the disease, and predicting outcomes. Most leukemia cells in AML patients show a protein called CLEC12A, making it a good sign of the disease and helpful for checking treatment progress.

CLEC12A is found to be highly present in AML stem cells, and research has shown that its level is closely related to the clinical features of AML patients. Leukemic stem cells (LSCs) in acute myeloid leukemia (AML) often produce a protein called CLEC12A, which makes them a target for treatment. CLEC12A is a reliable measure for tracking minimal residual disease (MRD) because its levels stay steady before, during, and after treatment. Finding CLEC12A-positive cells in blood or bone marrow helps doctors check how well treatment is working and if there are any leftover leukemia cells. This information helps them create tailored treatment plans.

CLEC12A as a Prognostic Marker

Recent studies indicate that the outcome of AML is closely linked to the amounts of CLEC12A mRNA. People with low levels of CLEC12A have sometimes been found to have more serious genetic features, lower rates of full recovery after treatment, and shorter lifespans in some studies. So, AML CLEC12A could be useful both for predicting outcomes and diagnosing the disease. By studying how CLEC12A is expressed in patient bone marrow samples, we can predict how well a treatment will work and the chance of it coming back.

Therapeutic Prospects of CLEC12A

Strategies for CLEC12A-based immunotherapies mainly include monoclonal antibodies, antibody-drug conjugates (ADCs), bispecific antibodies, and CAR-T cell treatment. These immunotherapy methods focus on leukemia cells that show CLEC12A, helping to eliminate harmful cells with strong treatment potential.

Research has shown that monoclonal antibodies aimed at CLEC12A can specifically kill AML cells through two processes: antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). ADCs combine chemotherapy drugs with antibodies to provide more precise and effective cancer treatment. As immunotherapy advances, treatments based on CLEC12A may bring new hope to people with AML.

References:

Morsink LM, Walter RB, et al. Prognostic and therapeutic role of CLEC12A in acute myeloid leukemia. Blood Rev. 2019 Mar;34:26-33.
McLeish KR, Fernandes MJ. Understanding inhibitory receptor function in neutrophils through the lens of CLEC12A. Immunol Rev. 2023 Mar;314(1):50-68.
Ma H, Padmanabhan IS, et al. Targeting CLL-1 for acute myeloid leukemia therapy. J Hematol Oncol. 2019 Apr 24;12(1):41.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry