Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM1IJO2)

• DOT Name: Interleukin-12 receptor subunit beta-1 (IL12RB1)
• Synonyms: IL-12 receptor subunit beta-1; IL-12R subunit beta-1; IL-12R-beta-1; IL-12RB1; IL-12 receptor beta component; CD antigen CD212
• Gene Name: IL12RB1
• Related Disease:
  Bacteremia
  Tuberculosis
  Adult lymphoma
  Allergic rhinitis
  Anemia
  Atopic dermatitis
  Autoimmune disease
  Behcet disease
  Brain ischaemia
  Candidiasis
  Capillary malformation
  Carcinoma of esophagus
  Chronic mucocutaneous candidiasis
  Diabetic kidney disease
  Endometriosis
  Esophageal cancer
  Gastric cancer
  Hidradenitis suppurativa
  Inflammatory bowel disease
  Intestinal disorder
  Lymphoma
  Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency
  Neoplasm of esophagus
  Non-hodgkin lymphoma
  Oral candidiasis
  Pediatric lymphoma
  Primary biliary cholangitis
  Psoriasis
  Psoriatic arthritis
  Pulmonary tuberculosis
  Sjogren syndrome
  Stomach cancer
  Systemic sclerosis
  Immunodeficiency
  Neuroblastoma
  Salmonella infection
  Type-1 diabetes
  Visceral leishmaniasis
  Advanced cancer
  Asthma
  Leishmaniasis
  Malaria
  Multi-drug resistant tuberculosis
  Neoplasm
  Osteomyelitis
  Severe acute respiratory syndrome (SARS)
• UniProt ID: I12R1_HUMAN
• PDB ID: 6WDP; 6WDQ
• Pfam ID: PF00041
• Sequence:
  MEPLVTWVVPLLFLFLLSRQGAACRTSECCFQDPPYPDADSGSASGPRDLRCYRISSDRY
  ECSWQYEGPTAGVSHFLRCCLSSGRCCYFAAGSATRLQFSDQAGVSVLYTVTLWVESWAR
  NQTEKSPEVTLQLYNSVKYEPPLGDIKVSKLAGQLRMEWETPDNQVGAEVQFRHRTPSSP
  WKLGDCGPQDDDTESCLCPLEMNVAQEFQLRRRQLGSQGSSWSKWSSPVCVPPENPPQPQ
  VRFSVEQLGQDGRRRLTLKEQPTQLELPEGCQGLAPGTEVTYRLQLHMLSCPCKAKATRT
  LHLGKMPYLSGAAYNVAVISSNQFGPGLNQTWHIPADTHTEPVALNISVGTNGTTMYWPA
  RAQSMTYCIEWQPVGQDGGLATCSLTAPQDPDPAGMATYSWSRESGAMGQEKCYYITIFA
  SAHPEKLTLWSTVLSTYHFGGNASAAGTPHHVSVKNHSLDSVSVDWAPSLLSTCPGVLKE
  YVVRCRDEDSKQVSEHPVQPTETQVTLSGLRAGVAYTVQVRADTAWLRGVWSQPQRFSIE
  VQVSDWLIFFASLGSFLSILLVGVLGYLGLNRAARHLCPPLPTPCASSAIEFPGGKETWQ
  WINPVDFQEEASLQEALVVEMSWDKGERTEPLEKTELPEGAPELALDTELSLEDGDRCKA
  KM
• Function: Functions as an interleukin receptor which binds interleukin-12 with low affinity and is involved in IL12 transduction. Associated with IL12RB2 it forms a functional, high affinity receptor for IL12. Associates also with IL23R to form the interleukin-23 receptor which functions in IL23 signal transduction probably through activation of the Jak-Stat signaling cascade.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  Pathways in cancer (hsa05200)
  Inflammatory bowel disease (hsa05321)
• Reactome Pathway:
  Interleukin-23 signaling (R-HSA-9020933)
  Interleukin-12 signaling (R-HSA-9020591)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bacteremia	DIS6N9RZ	Definitive	Genetic Variation	[1]
Tuberculosis	DIS2YIMD	Definitive	Biomarker	[2]
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[3]
Allergic rhinitis	DIS3U9HN	Strong	Genetic Variation	[4]
Anemia	DISTVL0C	Strong	Genetic Variation	[5]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[6]
Autoimmune disease	DISORMTM	Strong	Biomarker	[7]
Behcet disease	DISSYMBS	Strong	Biomarker	[8]
Brain ischaemia	DIS9Q4RT	Strong	Biomarker	[9]
Candidiasis	DISIRYMU	Strong	Genetic Variation	[10]
Capillary malformation	DISR6ZSG	Strong	Biomarker	[11]
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[12]
Chronic mucocutaneous candidiasis	DISPSGYF	Strong	Biomarker	[13]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[14]
Endometriosis	DISX1AG8	Strong	Genetic Variation	[15]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[12]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[16]
Hidradenitis suppurativa	DIS3ZNAK	Strong	Genetic Variation	[17]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[18]
Intestinal disorder	DISGPMUQ	Strong	Biomarker	[19]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[3]
Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency	DISUJN77	Strong	Autosomal recessive	[20]
Neoplasm of esophagus	DISOLKAQ	Strong	Genetic Variation	[12]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[21]
Oral candidiasis	DISAVKAH	Strong	Genetic Variation	[13]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[3]
Primary biliary cholangitis	DIS43E0O	Strong	Biomarker	[22]
Psoriasis	DIS59VMN	Strong	Biomarker	[23]
Psoriatic arthritis	DISLWTG2	Strong	Genetic Variation	[24]
Pulmonary tuberculosis	DIS6FLUM	Strong	Genetic Variation	[25]
Sjogren syndrome	DISUBX7H	Strong	Genetic Variation	[7]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[16]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[26]
Immunodeficiency	DIS093I0	moderate	Genetic Variation	[16]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[27]
Salmonella infection	DISTJ434	moderate	Altered Expression	[28]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[29]
Visceral leishmaniasis	DISTKEYK	moderate	Genetic Variation	[30]
Advanced cancer	DISAT1Z9	Disputed	Biomarker	[31]
Asthma	DISW9QNS	Limited	Genetic Variation	[32]
Leishmaniasis	DISABTW7	Limited	Biomarker	[33]
Malaria	DISQ9Y50	Limited	Altered Expression	[34]
Multi-drug resistant tuberculosis	DIS1A2CS	Limited	Altered Expression	[35]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[36]
Osteomyelitis	DIS0VUZL	Limited	Genetic Variation	[37]
Severe acute respiratory syndrome (SARS)	DISYW14W	Limited	Genetic Variation	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-12 receptor subunit beta-1 (IL12RB1).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interleukin-12 receptor subunit beta-1 (IL12RB1).	[40]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interleukin-12 receptor subunit beta-1 (IL12RB1).	[42]
Dinoprostone	DMTYOPD	Approved	Dinoprostone decreases the expression of Interleukin-12 receptor subunit beta-1 (IL12RB1).	[42]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Interleukin-12 receptor subunit beta-1 (IL12RB1).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-12 receptor subunit beta-1 (IL12RB1).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Interleukin-12 receptor subunit beta-1 (IL12RB1).	[46]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Interleukin-12 receptor subunit beta-1 (IL12RB1).	[47]
Dimethylallyl Diphosphate	DMP5I47	Investigative	Dimethylallyl Diphosphate increases the expression of Interleukin-12 receptor subunit beta-1 (IL12RB1).	[48]

2 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 Interleukin-12 receptor subunit beta-1 (IL12RB1).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Interleukin-12 receptor subunit beta-1 (IL12RB1).	[44]

References

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• [17] Haplotypes of IL-12R1 impact on the clinical phenotype of hidradenitis suppurativa.Cytokine. 2013 May;62(2):297-301. doi: 10.1016/j.cyto.2013.03.008. Epub 2013 Apr 2.
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• [19] Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12R1 Deficiency.J Clin Immunol. 2017 Oct;37(7):732-738. doi: 10.1007/s10875-017-0435-1. Epub 2017 Sep 1.
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• [22] Polymorphisms of IL12RB2 May Affect the Natural History of Primary Biliary Cholangitis: A Single Centre Study.J Immunol Res. 2017;2017:2185083. doi: 10.1155/2017/2185083. Epub 2017 Feb 19.
• [23] Gene-gene interactions in IL23/Th17 pathway contribute to psoriasis susceptibility in Chinese Han population.J Eur Acad Dermatol Venereol. 2013 Sep;27(9):1156-62. doi: 10.1111/j.1468-3083.2012.04683.x. Epub 2012 Aug 22.
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• [30] Visceral leishmaniasis in two patients with IL-12p40 and IL-12R1 deficiencies.Pediatr Blood Cancer. 2017 Jun;64(6). doi: 10.1002/pbc.26362. Epub 2016 Nov 22.
• [31] Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12-IFN-.Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11482-11487. doi: 10.1073/pnas.1705536114. Epub 2017 Oct 9.
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• [38] IL-12 RB1 genetic variants contribute to human susceptibility to severe acute respiratory syndrome infection among Chinese.PLoS One. 2008 May 14;3(5):e2183. doi: 10.1371/journal.pone.0002183.
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• [48] Vgamma9/Vdelta2 T lymphocytes in Italian patients with Beh?et's disease: evidence for expansion, and tumour necrosis factor receptor II and interleukin-12 receptor beta1 expression in active disease. Arthritis Res Ther. 2003;5(5):R262-8. doi: 10.1186/ar785. Epub 2003 Jun 30.