Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRTBH27)

• DOT Name: C-type lectin domain family 7 member A (CLEC7A)
• Synonyms: Beta-glucan receptor; C-type lectin superfamily member 12; Dendritic cell-associated C-type lectin 1; DC-associated C-type lectin 1; Dectin-1; CD antigen CD369
• Gene Name: CLEC7A
• Related Disease:
  Acute myelogenous leukaemia
  Arthritis
  Hereditary intrinsic factor deficiency
  Acute graft versus host disease
  Alzheimer disease
  Amyloidosis
  Arteriosclerosis
  Atherosclerosis
  Atopic dermatitis
  Autism spectrum disorder
  Autoimmune disease
  Bacterial infection
  Behcet disease
  Candidemia
  Candidiasis
  Cystic fibrosis
  Fungal keratitis
  Hepatitis B virus infection
  Inflammatory bowel disease
  Influenza
  Invasive candidiasis
  Keratitis
  Neoplasm
  Obesity
  Osteoarthritis
  Pneumocystis pneumonia
  Pneumonia
  Pneumonitis
  Psoriasis
  Rheumatoid arthritis
  Systemic lupus erythematosus
  T-cell lymphoma
  Tuberculosis
  Ulcerative colitis
  Vulvovaginal Candidiasis
  Chronic obstructive pulmonary disease
  Coronary atherosclerosis
  Hepatitis
  Lupus nephritis
  Myocardial ischemia
  Onychomycosis
  Chronic mucocutaneous candidiasis
  Advanced cancer
  Asthma
  Carcinoma of liver and intrahepatic biliary tract
  Colitis
  Invasive aspergillosis
  Invasive pulmonary aspergillosis
  Liver cancer
  Pancreatic cancer
• UniProt ID: CLC7A_HUMAN
• Pfam ID: PF00059
• Sequence:
  MEYHPDLENLDEDGYTQLHFDSQSNTRIAVVSEKGSCAASPPWRLIAVILGILCLVILVI
  AVVLGTMAIWRSNSGSNTLENGYFLSRNKENHSQPTQSSLEDSVTPTKAVKTTGVLSSPC
  PPNWIIYEKSCYLFSMSLNSWDGSKRQCWQLGSNLLKIDSSNELGFIVKQVSSQPDNSFW
  IGLSRPQTEVPWLWEDGSTFSSNLFQIRTTATQENPSPNCVWIHVSVIYDQLCSVPSYSI
  CEKKFSM
• Function: Lectin that functions as a pattern recognizing receptor (PRR) specific for beta-1,3-linked and beta-1,6-linked glucans, which constitute cell wall constituents from pathogenic bacteria and fungi. Necessary for the TLR2-mediated inflammatory response and activation of NF-kappa-B: upon beta-glucan binding, recruits SYK via its ITAM motif and promotes a signaling cascade that activates some CARD domain-BCL10-MALT1 (CBM) signalosomes, leading to the activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines. Enhances cytokine production in macrophages and dendritic cells. Mediates production of reactive oxygen species in the cell. Mediates phagocytosis of C.albicans conidia. Binds T-cells in a way that does not involve their surface glycans and plays a role in T-cell activation. Stimulates T-cell proliferation. Induces phosphorylation of SCIMP after binding beta-glucans.
• Tissue Specificity: Highly expressed in peripheral blood leukocytes and dendritic cells. Detected in spleen, bone marrow, lung, muscle, stomach and placenta.
• KEGG Pathway:
  Phagosome (hsa04145)
  Neutrophil extracellular trap formation (hsa04613)
  C-type lectin receptor sig.ling pathway (hsa04625)
  Tuberculosis (hsa05152)
• Reactome Pathway: CLEC7A (Dectin-1) signaling (R-HSA-5607764)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Arthritis	DIST1YEL	Definitive	Biomarker	[2]
Hereditary intrinsic factor deficiency	DISCZQBU	Definitive	Genetic Variation	[1]
Acute graft versus host disease	DIS8KLVM	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Amyloidosis	DISHTAI2	Strong	Genetic Variation	[5]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[6]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[6]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[7]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[8]
Autoimmune disease	DISORMTM	Strong	Biomarker	[9]
Bacterial infection	DIS5QJ9S	Strong	Biomarker	[10]
Behcet disease	DISSYMBS	Strong	Biomarker	[11]
Candidemia	DISVKFN7	Strong	Genetic Variation	[3]
Candidiasis	DISIRYMU	Strong	Genetic Variation	[12]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[13]
Fungal keratitis	DISA0XP5	Strong	Biomarker	[14]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[15]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[16]
Influenza	DIS3PNU3	Strong	Altered Expression	[17]
Invasive candidiasis	DIS5EI0L	Strong	Biomarker	[18]
Keratitis	DISMFOEI	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Obesity	DIS47Y1K	Strong	Biomarker	[21]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[9]
Pneumocystis pneumonia	DISFSOM3	Strong	Biomarker	[22]
Pneumonia	DIS8EF3M	Strong	Biomarker	[23]
Pneumonitis	DIS88E0K	Strong	Biomarker	[23]
Psoriasis	DIS59VMN	Strong	Biomarker	[7]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[24]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[24]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[25]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[26]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[27]
Vulvovaginal Candidiasis	DISRCR6D	Strong	Biomarker	[28]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[29]
Coronary atherosclerosis	DISKNDYU	moderate	Biomarker	[30]
Hepatitis	DISXXX35	moderate	Biomarker	[31]
Lupus nephritis	DISCVGPZ	moderate	Altered Expression	[32]
Myocardial ischemia	DISFTVXF	moderate	Biomarker	[30]
Onychomycosis	DISE4C4D	moderate	Genetic Variation	[33]
Chronic mucocutaneous candidiasis	DISPSGYF	Supportive	Autosomal dominant	[33]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[34]
Asthma	DISW9QNS	Limited	Genetic Variation	[35]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[36]
Colitis	DISAF7DD	Limited	Biomarker	[37]
Invasive aspergillosis	DISAI029	Limited	Genetic Variation	[38]
Invasive pulmonary aspergillosis	DISIZ0VJ	Limited	Biomarker	[39]
Liver cancer	DISDE4BI	Limited	Altered Expression	[36]
Pancreatic cancer	DISJC981	Limited	Biomarker	[40]

10 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 7 member A (CLEC7A).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of C-type lectin domain family 7 member A (CLEC7A).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of C-type lectin domain family 7 member A (CLEC7A).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of C-type lectin domain family 7 member A (CLEC7A).	[44]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of C-type lectin domain family 7 member A (CLEC7A).	[45]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of C-type lectin domain family 7 member A (CLEC7A).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of C-type lectin domain family 7 member A (CLEC7A).	[48]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of C-type lectin domain family 7 member A (CLEC7A).	[49]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of C-type lectin domain family 7 member A (CLEC7A).	[50]
Beta-D-Glucose	DM5IHYP	Investigative	Beta-D-Glucose decreases the expression of C-type lectin domain family 7 member A (CLEC7A).	[51]

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 7 member A (CLEC7A).	[47]

References

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