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C-type lectin domain family 12 member A

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 3081

Nomenclature: C-type lectin domain family 12 member A

Systematic Nomenclature: CD371

Family: C-type lectin-like receptors (CLRs)

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 265 12p13.31 CLEC12A C-type lectin domain family 12 member A
Mouse 1 267 6 F3 Clec12a C-type lectin domain family 12, member a
Rat 1 269 4q42 Clec12a C-type lectin domain family 12, member A
Previous and Unofficial Names Click here for help
C-type lectin domain family 12, member A | C-type lectin domain family 12, member a | C-type lectin domain family 12 | CLL-1 | dendritic cell-associated lectin 2 | DCAL-2 | myeloid inhibitory C-type lectin-like receptor | MICL
Database Links Click here for help
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
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Antibodies
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Antibody Sp. Action Value Parameter Reference
tepoditamab Peptide Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Binding 8.5 pKd 5
pKd 8.5 (Kd 3x10-9 M) [5]
Description: Binding affinity for hCLEC12A determined by surface plasmon resonance.
Immunopharmacology Comments
The CLEC12A protein is a negative regulator of granulocyte and monocyte function [2,4]. In vitro analyses indicate that CLEC12A may not act as a bona fide carbohydrate-sensitive pattern recognition receptor [7]. Studies using human cells suggests that CLEC12A synergises with signals from other receptors to facilitate dendritic cell (DC) responses, an action that modulates functions including DC migration and T cell activation.
CLEC12A is recognised as a novel prognostic and therapeutic marker of acute myeloid leukemia (AML) [1,6]. It is not expressed on normal early hematopoietic progenitors (including hematopoietic stem cells), so offers a highly selective target for AML immuno-oncology. One agent in the pharma pipeline is tepoditamab [5], a bispecific monoclonal antibody that binds both CLEC12A (on AML cells) and CD3 (on cytotoxic T cells), and which is expected to eradicate both AML blasts and their progenitors, to provide a more effective outcome for AML patients.
Cell Type Associations
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   classical monocyte (CL:0000860)
References:  4
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   granulocyte (CL:0000094)
References:  4
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
plasmacytoid dendritic cell (CL:0000784)
dendritic cell, human (CL:0001056)
plasmacytoid dendritic cell, human (CL:0001058)
Comment:  Expressed on mouse and human dendritic cell subsets.
References:  3
Immuno Process Associations
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0050776 regulation of immune response ISO
General Comments
The CLEC12A protein is a myeloid cell surface antigen that is regarded as a marker of acute myeloid leukemia (AML) stem cells [1,6], and as a novel target for the treatment of AML.

References

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1. Bakker AB, van den Oudenrijn S, Bakker AQ, Feller N, van Meijer M, Bia JA, Jongeneelen MA, Visser TJ, Bijl N, Geuijen CA et al.. (2004) C-type lectin-like molecule-1: a novel myeloid cell surface marker associated with acute myeloid leukemia. Cancer Res., 64 (22): 8443-50. [PMID:15548716]

2. Han Y, Zhang M, Li N, Chen T, Zhang Y, Wan T, Cao X. (2004) KLRL1, a novel killer cell lectinlike receptor, inhibits natural killer cell cytotoxicity. Blood, 104 (9): 2858-66. [PMID:15238421]

3. Lahoud MH, Proietto AI, Ahmet F, Kitsoulis S, Eidsmo L, Wu L, Sathe P, Pietersz S, Chang HW, Walker ID et al.. (2009) The C-type lectin Clec12A present on mouse and human dendritic cells can serve as a target for antigen delivery and enhancement of antibody responses. J. Immunol., 182 (12): 7587-94. [PMID:19494282]

4. Marshall AS, Willment JA, Lin HH, Williams DL, Gordon S, Brown GD. (2004) Identification and characterization of a novel human myeloid inhibitory C-type lectin-like receptor (MICL) that is predominantly expressed on granulocytes and monocytes. J. Biol. Chem., 279 (15): 14792-802. [PMID:14739280]

5. Van Loo PF, Doornbos R, Dolstra H, Shamsili S, Bakker L. (2015) Preclinical Evaluation of MCLA117, a CLEC12AxCD3 Bispecific Antibody Efficiently Targeting a Novel Leukemic Stem Cell Associated Antigen in AML. Blood, 126 (23): 325.

6. van Rhenen A, van Dongen GA, Kelder A, Rombouts EJ, Feller N, Moshaver B, Stigter-van Walsum M, Zweegman S, Ossenkoppele GJ, Jan Schuurhuis G. (2007) The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. Blood, 110 (7): 2659-66. [PMID:17609428]

7. Weis WI, Taylor ME, Drickamer K. (1998) The C-type lectin superfamily in the immune system. Immunol. Rev., 163: 19-34. [PMID:9700499]

How to cite this page

C-type lectin-like receptors (CLRs): C-type lectin domain family 12 member A. Last modified on 02/04/2019. Accessed on 28/11/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3081.