Disease:	Activated PI3K delta syndrome	1 target association: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta		more details » « hide details
Disease X-Refs:	OMIM: 615513 Orphanet: ORPHA397596
Target Comments Ligands key to symbols References phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta The effects of constitutive PI3Kδ activation in this syndrome are the opposite (or inverse) of the effects mediated by pharmacological PI3Kδ inhibitio ... leniolisib nemiralisib

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Disease:	Acute lymphocytic leukemia (ALL)	2 target associations: CD3e; CD19		more details » « hide details
Disease X-Refs:	OMIM: 613065
Target Comments Ligands key to symbols References CD3e CD3e is the molecular target of approved drug blinatumomab, as a treatment Philadelphia chromosome-negative precursor B-cell ALL CD19 CD19 is one of the molecular targets of the bi-specific antibody drug blinatumomab (also binds CD3e).

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Disease:	Acute myeloid leukemia	3 target associations: KIT proto-oncogene, receptor tyrosine kinase; fms related receptor tyrosine kinase 3; isocitrate dehydrogenase (NADP(+)) 1		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:9119 OMIM: 601626 Orphanet: ORPHA519
Target Comments Ligands key to symbols References KIT proto-oncogene, receptor tyrosine kinase KIT mutations have been identified in founding clones from AML patients, which suggests that KIT mutations initiate development of AML. 45 fms related receptor tyrosine kinase 3 Somatic mutations in FLT3 have been found in cases of AML Idenification of FLT3 mutations in subclones of AML patient-derived cells, suggests that the ... midostaurin crenolanib 8 isocitrate dehydrogenase (NADP(+)) 1 Mutant IDH1 isoforms are found in 6 to 10% of cases of AML and in a variety of solid tumours, and make these tumours susceptible to IDH1 inhibitor the ... ivosidenib 13,39,41,46,57,69

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Disease:	Allograft rejection	1 target association: CD80		more details » « hide details
Disease X-Refs:
Target Comments Ligands key to symbols References CD80 CD80 is a primary target of the approved anti-rejection drug belatacept. belatacept

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Disease:	Asthma	6 target associations: MMP2; MMP9; MMP8 ...		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:2841 OMIM: 600807
Target Comments Ligands key to symbols References MMP2 MMP2 and MMP9 can promote the egress of inflammatory cells into airway lumen, suggesting a protective anti-inflammatory role in asthma. MMP2/MMP9 gela ... 10 MMP9 MMP2 and MMP9 can promote the egress of inflammatory cells into airway lumen, suggesting a protective anti-inflammatory role in asthma. MMP2/MMP9 gela ... 10 MMP8 MMP8 plays a protective role in asthma by promoting the clearance of recruited neutrophils. 22 MMP12 a common serine variant of the MMP12 gene in human (rs652438) causes more aggressive extracellular matrix degradation and is positively associated wit ... 47 ADAM33 ADAM33 is implicated in the pathology of asthma. 63 ACKR1 ACKR1 may play a role in the temporal regulation of asthma pathophysiology and symptoms. 11

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Disease:	Atopic dermatitis	1 target association: INPP5D		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:3310 OMIM: 603165
Target Comments Ligands key to symbols References INPP5D Target of activating compounds with potential immunosuppressant action. Phase 2 with rosiptor has been completed for atopic dermatitis.

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Disease:	Autoimmune lymphoproliferative syndrome; ALPS	1 target association: Fas		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:6688 OMIM: 601859 Orphanet: ORPHA3261
Target Comments Ligands key to symbols References Fas Type IA ALPS is caused by mutations in Fas receptor (CD95). 7

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Disease:	Behcet syndrome	2 target associations: CIITA; nucleotide binding oligomerization domain containing 1		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:13241 OMIM: 109650 Orphanet: ORPHA117
Target Comments Ligands key to symbols References CIITA Genetic variations in CIITA are associated with Behcet's disease in a Chinese Han population, and confer disease susceptibility. 38 nucleotide binding oligomerization domain containing 1 Genetic variations in NOD1 are associated with Behcet's disease in a Chinese Han population, and confer disease susceptibility. 38

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Disease:	Charcot-Marie-Tooth disease type 2A	1 target association: mitofusin 2		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:0111557 OMIM: 617087 Orphanet: ORPHA99947
Target Comments Ligands key to symbols References mitofusin 2

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Disease:	Chronic lymphocytic leukemia	1 target association: CD20 (membrane-spanning 4-domains, subfamily A, member 1)		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:1040 OMIM: 151400 Orphanet: ORPHA67038
Target Comments Ligands key to symbols References CD20 (membrane-spanning 4-domains, subfamily A, member 1) CD20 is the molecular target of the CLL therapeutics ofatumumab and obinutuzumab. ofatumumab rituximab obinutuzumab veltuzumab

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Disease:	Colitis	1 target association: 5-HT1A receptor		more details » « hide details
Disease X-Refs:
Target Comments Ligands key to symbols References 5-HT1A receptor Serotonin acting via 5-HT1A receptors plays a key role in the pathogenesis of experimental colitis 18

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Disease:	Crohn's disease	1 target association: heat shock protein family A (Hsp70) member 1 like		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:8778 OMIM: 266600 Orphanet: ORPHA206
Target Comments Ligands key to symbols References heat shock protein family A (Hsp70) member 1 like Genetic mutations that cause amino acid changes in the HSPA1L protein have been identified in patients with CD. 60

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Disease:	Graft versus host disease	1 target association: CD86		more details » « hide details
Disease X-Refs:
Target Comments Ligands key to symbols References CD86 CD86 is a primary target of the approved anti-rejection drug belatacept.

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Disease:	Immunodeficiency 9	1 target association: Orai1		more details » « hide details
Disease X-Refs:	OMIM: 612782
Target Comments Ligands key to symbols References Orai1 Mutations in the human ORAI1 gene cause defective T cell activation and immune dysfunction. 16,51

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Disease:	Immunodeficiency, developmental delay, and hypohomocysteinemia (IMDDHH)	1 target association: nuclear factor, erythroid 2 like 2		more details » « hide details
Disease X-Refs:	OMIM: 617744
Target Comments Ligands key to symbols References nuclear factor, erythroid 2 like 2 IMDDHH is associated with heterozygous missense mutations in the NFE2L2 gene. The mutations detected affect the N-terminal Neh2 domain of NRF2 ... 27

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Disease:	Interstitial cystitis	1 target association: INPP5D		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:13949
Target Comments Ligands key to symbols References INPP5D Phase 3 evaluating the SHIP1 activator rosiptor is underway (see NCT02858453).

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Disease:	Irritable bowel syndrome	2 target associations: MMP3; MMP9		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:9778
Target Comments Ligands key to symbols References MMP3 MMP3 has been shown to be causative in the tissue injury in IBD. Several functional polymorphisms in the promoter region of the MMP3 gene are ... 29,52-53 MMP9 MMP9 is suggested to be implicated in fistula formation in IBD. Upregulated mucosal MMP9 expression correlates with disease severity. MMP9 selective i ... 30,33,42

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Disease:	Kawasaki disease	1 target association: Caspase 3		more details » « hide details
Disease X-Refs:	OMIM: 611775
Target Comments Ligands key to symbols References Caspase 3 Caspase 3 mutations confer susceptibility to KD. 49

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Disease:	leukocyte adhesion deficiency type 1	1 target association: integrin, beta 2 subunit (complement component 3 receptor 3 and 4 subunit)		more details » « hide details
Disease X-Refs:	OMIM: 116920
Target Comments Ligands key to symbols References integrin, beta 2 subunit (complement component 3 receptor 3 and 4 subunit) Multiple inherited mutations in the integrin β2 protein (CD18) that reduce expression or function have been identified as the causative factor in ... 14-15,59

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Disease:	Mastocytosis	1 target association: KIT proto-oncogene, receptor tyrosine kinase		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:350
Target Comments Ligands key to symbols References KIT proto-oncogene, receptor tyrosine kinase Constitutively active KIT D816V is associated with mast cell clonal disorders. KIT D816V detection in blood and bone marrow is important for diagnosin ... masitinib 6,21,48,61

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Disease:	Multiple sclerosis	3 target associations: BAFF receptor; MMP9; regulator of G-protein signaling 10		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:2377 OMIM: 126200 Orphanet: ORPHA802
Target Comments Ligands key to symbols References BAFF receptor The anti-BAFF-R mAb VAY736 has completed Phase 2 clinical evaluation in RRMS- see NCT02038049. 55 MMP9 MMP9 is upregulated in cerebrospinal fluid (CSF), blood and brain tissue of MS patients, can be a useful biomarker and expression level is reduced in ... 2,5,68 regulator of G-protein signaling 10 36

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Disease:	Myelofibrosis	1 target association: Janus kinase 2		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:4971 OMIM: 254450 Orphanet: ORPHA824
Target Comments Ligands key to symbols References Janus kinase 2 Somatic mutations in the JAK2 gene have been identified in many cases of myelofibrosis. ruxolitinib 4,31

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Disease:	non-Hodgkin lymphoma	1 target association: CD20 (membrane-spanning 4-domains, subfamily A, member 1)		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:0060060 OMIM: 605027
Target Comments Ligands key to symbols References CD20 (membrane-spanning 4-domains, subfamily A, member 1) CD20 is the molecular target of the B cell NHL therapeutic ibritumomab tiuxetan. ibritumomab tiuxetan tositumomab

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Disease:	Osteoarthritis	5 target associations: MMP13; MMP3; ADAMTS5 ...		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:8398
Target Comments Ligands key to symbols References MMP13 The collagenolytic MMPs 3 and 13 are strongly implicated in cartilage destruction in OA. AZD6605 62 MMP3 The collagenolytic MMPs 3 and 13 are strongly implicated in cartilage destruction in OA. 62 ADAMTS5 ADAMTS4 and -5 are major players in development of OA. 58 ADAMTS4 ADAMTS4 and -5 are major players in development of OA. In human OA ADAMTS4 is induced by IL-1αand TNF-α, two cytokines involved in OA. 58,65 ADAMTS5 Preclinical molecular target for OA. Anti-ADAMTS5-selective monoclonal antibodies CRB0017 and GSK2394002 have indicated some efficacy in OA disease m ... 12,34

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Disease:	Osteoporosis	1 target association: regulator of G-protein signaling 10		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:11476 OMIM: 166710
Target Comments Ligands key to symbols References regulator of G-protein signaling 10 66-67

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Disease:	Ovarian cancer	1 target association: regulator of G-protein signaling 10		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:2394 OMIM: 167000
Target Comments Ligands key to symbols References regulator of G-protein signaling 10 1,9,26

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Disease:	Parkinson Disease	1 target association: regulator of G-protein signaling 10		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:14330 OMIM: 168600
Target Comments Ligands key to symbols References regulator of G-protein signaling 10 35,37

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Disease:	Pemphigus	1 target association: CD20 (membrane-spanning 4-domains, subfamily A, member 1)		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:9182
Target Comments Ligands key to symbols References CD20 (membrane-spanning 4-domains, subfamily A, member 1) CD20 is the molecular target of the antibody veltuzumab. rituximab veltuzumab

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Disease:	Periodontal disease	1 target association: regulator of G-protein signaling 10		more details » « hide details
Disease X-Refs:
Target Comments Ligands key to symbols References regulator of G-protein signaling 10 66

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Disease:	Polycythemia vera	1 target association: Janus kinase 2		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:8997 OMIM: 263300 Orphanet: ORPHA729
Target Comments Ligands key to symbols References Janus kinase 2 Most cases of PV are associated with a somatic mutation in the JAK2 gene. The JAK2 V617F mutation causes constitutive tyrosine phosphorylation activit ... ruxolitinib 4,28,31

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Disease:	Psoriasis	2 target associations: CD2; CD6		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:8893
Target Comments Ligands key to symbols References CD2 CD2 is the molecular target of alefacept, a drug that was approved for the treatment of moderate to severe plaque psoriasis. alefacept CD6 CD6 is the molecular target of itolizumab, a drug approved for the treatment of chronic plaque psoriasis. itolizumab

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Disease:	Relapsing-remitting multiple sclerosis	1 target association: CD20 (membrane-spanning 4-domains, subfamily A, member 1)		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:2378
Target Comments Ligands key to symbols References CD20 (membrane-spanning 4-domains, subfamily A, member 1) CD20 is the molecular target of the RRMS therapeutic ocrelizumab. ocrelizumab

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Disease:	Rheumatoid arthritis	11 target associations: BAFF receptor; MMP1; MMP3 ...		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:7148 OMIM: 180300
Target Comments Ligands key to symbols References BAFF receptor Molecular target for RA- see NCT02675803 which was designed to evaluate clinical efficacy of anti-BAFF-R mAb VAY736 in RA patients. MMP1 Serum level of MMP1 correlates with disease activity in RA. 20 MMP3 Serum level of MMP3 correlates with disease activity in RA, and is used as a biomarker for predicting bone and cartilage damage and evaluating therape ... 17,20 MMP14 MMP14 (also called MT1-MMP) is highly expressed in fibroblast-like synoviocytes and macrophages from patients with RA, and is reckoned to be one of th ... 50,56 ADAMTS4 ADAMTS4 is involved in RA pathogenesis. 43,54 ADAMTS5 ADAMTS5 is involved in RA pathogenesis. 43,54 CD86 CD86 is a primary target of the ligand abatacept, which is clinically approved for the treatment of rheumatoid arthritis. abatacept 64 CD80 CD80 is a primary target of the ligand abatacept, which is clinically approved for the treatment of rheumatoid arthritis. abatacept 64 NLRC5 A study by Liu et al. (2017) found that NLRC5 is upregulated in synovial tissues and cells of AA animal models, NLRC5 silencing inhibits inflam ... 40 BLT2 receptor The expression of LTB4R (BLT1) and LTB4R2 (BLT2) mRNA is elevated in synovial tissues of RA patients compared to OA patients., ... 23 BLT1 receptor The expression of LTB4R (BLT1) and LTB4R2 (BLT2) mRNA is elevated in synovial tissues of RA patients compared to OA patients., ... 23

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Disease:	Schizophrenia	1 target association: regulator of G-protein signaling 10		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:5419 OMIM: 181500 Orphanet: ORPHA3140
Target Comments Ligands key to symbols References regulator of G-protein signaling 10 Possible link to schizophrenia and depression. 19,25

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Disease:	Sjögren's syndrome	1 target association: BAFF receptor		more details » « hide details
Disease X-Refs:	Orphanet: ORPHA378
Target Comments Ligands key to symbols References BAFF receptor Molecular target for SS- see NCT02962895 which is designed to evaluate clinical efficacy of anti-BAFF-R mAb VAY736 in SS patients.

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Disease:	Ulcerative colitis	1 target association: heat shock protein family A (Hsp70) member 1 like		more details » « hide details
Disease X-Refs:	Disease Ontology: DOID:8577 OMIM: 266600 Orphanet: ORPHA771
Target Comments Ligands key to symbols References heat shock protein family A (Hsp70) member 1 like Genetic mutations that cause amino acid changes in the HSPA1L protein have been identified in patients with UC. 60

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Disease:	Vascular injury	1 target association: regulator of G-protein signaling 10		more details » « hide details
Disease X-Refs:
Target Comments Ligands key to symbols References regulator of G-protein signaling 10 24,44

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Disease:	WHIM syndrome	1 target association: CXCR4		more details » « hide details
Disease X-Refs:	OMIM: 193670 Orphanet: ORPHA51636
Target Comments Ligands key to symbols References CXCR4 Mutations in CXCR4 that augment its activity have been identified in patients with WHIM syndrome. Such mutations can impair CXCR4/β-arrestin inte ... mavorixafor 3,32

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