CLEC12A

C-type lectin domain family 12 member A is a protein that in humans is encoded by the CLEC12A gene.^[5]

CLEC12A
Identifiers
Aliases	CLEC12A, CLL-1, CLL1, DCAL-2, MICL, CD371, C-type lectin domain family 12 member A
External IDs	OMIM: 612088; MGI: 3040968; HomoloGene: 51378; GeneCards: CLEC12A; OMA:CLEC12A - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12p13.31 Start 9,951,316 bp[1] End 9,995,694 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6|6 F3 Start 129,319,654 bp[2] End 129,342,266 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte granulocyte bone marrow trabecular bone blood bone marrow cell spleen appendix right lung testicle Top expressed in granulocyte primary oocyte left lobe of liver secondary oocyte zygote bone marrow spleen right lobe of liver pharynx placenta More reference expression data BioGPS n/a
Gene ontology Molecular function carbohydrate binding Cellular component membrane integral component of membrane plasma membrane specific granule membrane tertiary granule membrane Biological process neutrophil degranulation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 160364 232413 Ensembl ENSG00000172322 ENSMUSG00000053063 UniProt Q5QGZ9 Q504P2 RefSeq (mRNA) NM_001207010 NM_001300730 NM_138337 NM_201623 NM_201625 NM_177686 RefSeq (protein) NP_001193939 NP_001287659 NP_612210 NP_963917 NP_808354 Location (UCSC) Chr 12: 9.95 – 10 Mb Chr 6: 129.32 – 129.34 Mb PubMed search [3] [4]
Wikidata
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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.^[5]

CLEC12A, also known as MICL, is inhibitory C-type lectin-like receptor. It contains ITIM motif in cytoplasmic tail that can associate with signaling phosphatases SHP-1 and SHP-2.^[6][7]

There are two types, human (hMICL) and murine (mMICL). Human MICL is expressed as a monomer primarily on myeloid cells, including granulocytes, monocytes, macrophages and dendritic cells.^[6]

Murine MICL is expressed as dimer on granulocytes, monocytes but also on B lymphocytes and can be also found on NK cells surface in bone marrow.^[8]

Use in therapy

In the immunotherapy of acute myeloid leukemia (AML), CLL-1 becomes one of the target due to its high expression in AML cells while being absent in normal hematopoietic stem cells. CLL-1 is also expressed on the surface of leukemic stem cells (LSC), which possesses the ability to indefinitely self-renew, produce plenty of leukemic cells and are associated with leukemia relapses.^[9][10]

Scientists are working on various therapeutic approaches using CLL-1 as a target for AML. One of them is development of bispecific antibodies such as CD3/CLL-1 antibody. It can recruit unstimulated primary T cells in patients against cancer cells with CLL-1 on surface.^[11]

Other way is development of CAR T cells specific for CLL-1 antigen. This principle showed efficient and specific anti-leukemia activity to AML cell lines from AML patients, as well as in mouse model.^[12][13]