Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT31629M)

• DOT Name: C-type lectin domain family 12 member A (CLEC12A)
• Synonyms: C-type lectin-like molecule 1; CLL-1; Dendritic cell-associated lectin 2; DCAL-2; Myeloid inhibitory C-type lectin-like receptor; MICL; CD antigen CD371
• Gene Name: CLEC12A
• UniProt ID: CL12A_HUMAN
• Pfam ID: PF00059
• Sequence:
  MSEEVTYADLQFQNSSEMEKIPEIGKFGEKAPPAPSHVWRPAALFLTLLCLLLLIGLGVL
  ASMFHVTLKIEMKKMNKLQNISEELQRNISLQLMSNMNISNKIRNLSTTLQTIATKLCRE
  LYSKEQEHKCKPCPRRWIWHKDSCYFLSDDVQTWQESKMACAAQNASLLKINNKNALEFI
  KSQSRSYDYWLGLSPEEDSTRGMRVDNIINSSAWVIRNAPDLNNMYCGYINRLYVQYYHC
  TYKKRMICEKMANPVQLGSTYFREA
• Function: Cell surface receptor that modulates signaling cascades and mediates tyrosine phosphorylation of target MAP kinases.
• Tissue Specificity: Detected in normal myeloid cells and in acute myeloid leukemia cells. Detected in neutrophils, eosinophils, monocytes and dendritic cells. Detected in spleen macrophage-rich red pulp and in lymph node (at protein level). Detected in peripheral blood leukocytes, dendritic cells, bone marrow, monocytes, mononuclear leukocytes and macrophages.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-type lectin domain family 12 member A (CLEC12A).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of C-type lectin domain family 12 member A (CLEC12A).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of C-type lectin domain family 12 member A (CLEC12A).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of C-type lectin domain family 12 member A (CLEC12A).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C-type lectin domain family 12 member A (CLEC12A).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of C-type lectin domain family 12 member A (CLEC12A).	[7]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of C-type lectin domain family 12 member A (CLEC12A).	[5]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [6] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [7] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.