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Target id: 3081
Nomenclature: C-type lectin domain family 12 member A
Systematic Nomenclature: CD371
Gene and Protein Information | ||||||
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 |
Database Links | |
Alphafold | Q5QGZ9 (Hs), Q504P2 (Mm) |
Ensembl Gene | ENSG00000172322 (Hs), ENSMUSG00000053063 (Mm), ENSRNOG00000054860 (Rn) |
Entrez Gene | 160364 (Hs), 232413 (Mm), 680338 (Rn) |
Human Protein Atlas | ENSG00000172322 (Hs) |
KEGG Gene | hsa:160364 (Hs), mmu:232413 (Mm), rno:680338 (Rn) |
OMIM | 612088 (Hs) |
Pharos | Q5QGZ9 (Hs) |
RefSeq Nucleotide | NM_138337 (Hs), NM_177686 (Mm), NM_001134716 (Rn) |
RefSeq Protein | NP_612210 (Hs), NP_808354 (Mm), NP_001128188 (Rn) |
UniProtKB | Q5QGZ9 (Hs), Q504P2 (Mm) |
Wikipedia | CLEC12A (Hs) |
Download all structure-activity data for this target as a CSV file
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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 | ||||||||
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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. |
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]
C-type lectin-like receptors (CLRs): C-type lectin domain family 12 member A. Last modified on 02/04/2019. Accessed on 03/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3081.