Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUGTR0H)

• DOT Name: C-type lectin domain family 4 member G (CLEC4G)
• Synonyms: Liver and lymph node sinusoidal endothelial cell C-type lectin; LSECtin
• Gene Name: CLEC4G
• Related Disease:
  Hepatocellular carcinoma
  Breast cancer
  Breast carcinoma
  Ebola virus infection
  Metastatic malignant neoplasm
• UniProt ID: CLC4G_HUMAN
• Pfam ID: PF00059
• Sequence:
  MDTTRYSKWGGSSEEVPGGPWGRWVHWSRRPLFLALAVLVTTVLWAVILSILLSKASTER
  AALLDGHDLLRTNASKQTAALGALKEEVGDCHSCCSGTQAQLQTTRAELGEAQAKLMEQE
  SALRELRERVTQGLAEAGRGREDVRTELFRALEAVRLQNNSCEPCPTSWLSFEGSCYFFS
  VPKTTWAAAQDHCADASAHLVIVGGLDEQGFLTRNTRGRGYWLGLRAVRHLGKVQGYQWV
  DGVSLSFSHWNQGEPNDAWGRENCVMMLHTGLWNDAPCDSEKDGWICEKRHNC
• Function: Binds mannose, N-acetylglucosamine (GlcNAc) and fucose, but not galactose, in a Ca(2+)-dependent manner, in vitro; (Microbial infection) Acts as a receptor for Japanese encephalitis virus; (Microbial infection) Acts as a receptor for Ebolavirus; (Microbial infection) Acts as a receptor for SARS-CoV; (Microbial infection) Acts as a receptor for Lassa virus and Lymphocytic choriomeningitis virus glycoprotein.
• Tissue Specificity: Expressed exclusively in fetal and adult liver and in lymph nodes. Specifically expressed by endothelial cells lining lymph node and liver sinuses (at protein level).
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Limited	Biomarker	[2]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[2]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of C-type lectin domain family 4 member G (CLEC4G).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of C-type lectin domain family 4 member G (CLEC4G).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of C-type lectin domain family 4 member G (CLEC4G).	[6]

References

• [1] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [2] LSECtin on tumor-associated macrophages enhances breast cancer stemness via interaction with its receptor BTN3A3.Cell Res. 2019 May;29(5):365-378. doi: 10.1038/s41422-019-0155-6. Epub 2019 Mar 11.
• [3] The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein.PLoS Pathog. 2016 Mar 4;12(3):e1005487. doi: 10.1371/journal.ppat.1005487. eCollection 2016 Mar.
• [4] C-type lectins facilitate tumor metastasis.Oncol Lett. 2017 Jan;13(1):13-21. doi: 10.3892/ol.2016.5431. Epub 2016 Nov 24.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] 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.