Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAIA3NA)

• DOT Name: NLR family CARD domain-containing protein 4 (NLRC4)
• Synonyms: CARD, LRR, and NACHT-containing protein; CED-4-like protein Clan; Caspase recruitment domain-containing protein 12; Ice protease-activating factor; Ipaf
• Gene Name: NLRC4
• Related Disease:
  Periodic fever-infantile enterocolitis-autoinflammatory syndrome
  Acute coronary syndrome
  Advanced cancer
  Alzheimer disease
  Anthrax
  Astrocytoma
  Autoinflammatory syndrome
  Bacillary dysentery
  Bacterial infection
  Breast carcinoma
  Chorioamnionitis
  CINCA syndrome
  Colitis
  Colorectal carcinoma
  Cystic fibrosis
  Diabetic kidney disease
  Familial cold autoinflammatory syndrome 4
  Glioma
  Hereditary periodic fever syndrome
  Hyperglycemia
  Influenza
  Melioidosis
  Multiple sclerosis
  Neoplasm
  Non-alcoholic fatty liver disease
  Pneumonia
  Pneumonitis
  Relapsing-remitting multiple sclerosis
  Salmonella infection
  Systemic lupus erythematosus
  Tuberculosis
  Urinary tract infection
  Arthritis
  Enterocolitis
  Hepatocellular carcinoma
  Keratitis
  Obesity
  Vulvovaginal Candidiasis
  Crohn disease
  Familial cold autoinflammatory syndrome
  Glaucoma/ocular hypertension
  Inflammation
  Melanoma
  Periodontal disease
  Periodontitis
  Streptococcal pneumonia
  Stroke
• UniProt ID: NLRC4_HUMAN
• PDB ID: 6K8J; 6MKS; 6N1I
• Pfam ID: PF00619 ; PF05729 ; PF17889
• Sequence:
  MNFIKDNSRALIQRMGMTVIKQITDDLFVWNVLNREEVNIICCEKVEQDAARGIIHMILK
  KGSESCNLFLKSLKEWNYPLFQDLNGQSLFHQTSEGDLDDLAQDLKDLYHTPSFLNFYPL
  GEDIDIIFNLKSTFTEPVLWRKDQHHHRVEQLTLNGLLQALQSPCIIEGESGKGKSTLLQ
  RIAMLWGSGKCKALTKFKFVFFLRLSRAQGGLFETLCDQLLDIPGTIRKQTFMAMLLKLR
  QRVLFLLDGYNEFKPQNCPEIEALIKENHRFKNMVIVTTTTECLRHIRQFGALTAEVGDM
  TEDSAQALIREVLIKELAEGLLLQIQKSRCLRNLMKTPLFVVITCAIQMGESEFHSHTQT
  TLFHTFYDLLIQKNKHKHKGVAASDFIRSLDHCGDLALEGVFSHKFDFELQDVSSVNEDV
  LLTTGLLCKYTAQRFKPKYKFFHKSFQEYTAGRRLSSLLTSHEPEEVTKGNGYLQKMVSI
  SDITSTYSSLLRYTCGSSVEATRAVMKHLAAVYQHGCLLGLSIAKRPLWRQESLQSVKNT
  TEQEILKAININSFVECGIHLYQESTSKSALSQEFEAFFQGKSLYINSGNIPDYLFDFFE
  HLPNCASALDFIKLDFYGGAMASWEKAAEDTGGIHMEEAPETYIPSRAVSLFFNWKQEFR
  TLEVTLRDFSKLNKQDIRYLGKIFSSATSLRLQIKRCAGVAGSLSLVLSTCKNIYSLMVE
  ASPLTIEDERHITSVTNLKTLSIHDLQNQRLPGGLTDSLGNLKNLTKLIMDNIKMNEEDA
  IKLAEGLKNLKKMCLFHLTHLSDIGEGMDYIVKSLSSEPCDLEEIQLVSCCLSANAVKIL
  AQNLHNLVKLSILDLSENYLEKDGNEALHELIDRMNVLEQLTALMLPWGCDVQGSLSSLL
  KHLEEVPQLVKLGLKNWRLTDTEIRILGAFFGKNPLKNFQQLNLAGNRVSSDGWLAFMGV
  FENLKQLVFFDFSTKEFLPDPALVRKLSQVLSKLTFLQEARLVGWQFDDDDLSVITGAFK
  LVTA
• Function: Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis. The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria.
• Tissue Specificity: Isoform 2 is expressed ubiquitously, although highly expressed in lung and spleen. Isoform 1 is highly expressed in lung, followed by leukocytes especially monocytes, lymph node, colon, brain, prostate, placenta, spleen, bone marrow and fetal liver. Isoform 4 is only detected in brain.
• KEGG Pathway:
  NOD-like receptor sig.ling pathway (hsa04621)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Legionellosis (hsa05134)
  Yersinia infection (hsa05135)
• Reactome Pathway:
  The IPAF inflammasome (R-HSA-844623)
  TP53 Regulates Transcription of Caspase Activators and Caspases (R-HSA-6803207)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Periodic fever-infantile enterocolitis-autoinflammatory syndrome	DISCVB63	Definitive	Autosomal dominant	[1]
Acute coronary syndrome	DIS7DYEW	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Anthrax	DISFPT78	Strong	Biomarker	[5]
Astrocytoma	DISL3V18	Strong	Altered Expression	[3]
Autoinflammatory syndrome	DISCMCGL	Strong	Genetic Variation	[6]
Bacillary dysentery	DISFZHKN	Strong	Biomarker	[7]
Bacterial infection	DIS5QJ9S	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[9]
Chorioamnionitis	DISL1D9U	Strong	Altered Expression	[10]
CINCA syndrome	DISU6RZC	Strong	Genetic Variation	[11]
Colitis	DISAF7DD	Strong	Biomarker	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[14]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[15]
Familial cold autoinflammatory syndrome 4	DISNPGTL	Strong	Autosomal dominant	[16]
Glioma	DIS5RPEH	Strong	Altered Expression	[3]
Hereditary periodic fever syndrome	DISS9RWQ	Strong	Biomarker	[1]
Hyperglycemia	DIS0BZB5	Strong	Posttranslational Modification	[17]
Influenza	DIS3PNU3	Strong	Biomarker	[18]
Melioidosis	DISB13HR	Strong	Genetic Variation	[19]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[20]
Neoplasm	DISZKGEW	Strong	Altered Expression	[21]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[22]
Pneumonia	DIS8EF3M	Strong	Biomarker	[19]
Pneumonitis	DIS88E0K	Strong	Biomarker	[19]
Relapsing-remitting multiple sclerosis	DISSXFCF	Strong	Biomarker	[23]
Salmonella infection	DISTJ434	Strong	Altered Expression	[24]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[25]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[26]
Urinary tract infection	DISMT6UV	Strong	Biomarker	[27]
Arthritis	DIST1YEL	moderate	Altered Expression	[16]
Enterocolitis	DISYACTL	moderate	Genetic Variation	[28]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[29]
Keratitis	DISMFOEI	moderate	Biomarker	[30]
Obesity	DIS47Y1K	moderate	Altered Expression	[21]
Vulvovaginal Candidiasis	DISRCR6D	moderate	Biomarker	[31]
Crohn disease	DIS2C5Q8	Disputed	Genetic Variation	[32]
Familial cold autoinflammatory syndrome	DISAPE70	Limited	Genetic Variation	[33]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[34]
Inflammation	DISJUQ5T	Limited	Biomarker	[35]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[36]
Periodontal disease	DISJQHVN	Limited	Biomarker	[37]
Periodontitis	DISI9JOI	Limited	Biomarker	[37]
Streptococcal pneumonia	DIS2EKMJ	Limited	Biomarker	[38]
Stroke	DISX6UHX	Limited	Biomarker	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of NLR family CARD domain-containing protein 4 (NLRC4).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of NLR family CARD domain-containing protein 4 (NLRC4).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of NLR family CARD domain-containing protein 4 (NLRC4).	[43]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of NLR family CARD domain-containing protein 4 (NLRC4).	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of NLR family CARD domain-containing protein 4 (NLRC4).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of NLR family CARD domain-containing protein 4 (NLRC4).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of NLR family CARD domain-containing protein 4 (NLRC4).	[46]

References

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