Identification of Novel Therapeutic Molecular Targets in Inflammatory Bowel Disease by Using Genetic Databases

Figures & data

Table 1 Genes Overlapping in IBD (UC and CD) and Its Extra-Intestinal Manifestations (Uveitis, Arthritis, Primary Sclerosing Cholangitis and Skin Manifestations – Pyoderma Gangrenosum); with the Individual Gene, Specific Disease Processes, and Gene Function Listed

SN #	Genes	Conditions	Pathways*
1	IL17A	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	Mucin expression in CF via IL6, IL17, IL27 mediated pathway, PDGF signaling, Th17 differentiation, RA pathway
2	NOD2	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	Activated TLR4 signaling, NF-kappaB Pathway, NOD Pathway, Deubiquitination
3	TNF	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	TNFR1 pathway, IL6 pathway, STAT 3 pathway, Death Receptor signaling, Toll Like Receptor signaling
4	CCR6	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	Akt Signaling, Defensins, GPCR Signaling
5	CXCL8	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	PEDF induced signaling, Toll-like receptor signaling pathway, TGF-Beta Pathway, GPCR ligand binding
6	1L1B	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	PEDF induced signaling, Toll-like receptor signaling pathway, TGF-Beta Pathway, GPCR ligand binding, ERK Signaling
7	NLRP3	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	NLR signaling pathway, Innate immune system, metabolism of proteins, Toll-like receptor signaling pathway
8	MPO	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	Innate immune system, Folate Metabolism, NF-kappaB Pathway, Cytochrome P450
9	IL1RN	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	NF-kappaB Pathway, IL1 Signaling, PEDF induced signaling, Toll-like receptor signaling pathway
10	ITGB2	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	MAPK Erk Pathway, PPAR Pathway, Rho Family GTPases, FAK1 signaling, Actin nucleation, and Branching
11	PTPN22	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	PAK pathway, CTLA4 signaling, NF-kappaB Pathway
12	MMP9	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	Matrix Metalloproteinase’s, Integrin pathway, Degradation of extracellular matrix, Innate immune system
13	ICAM1	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	VCAM-1/CD106 signaling, Folate metabolism, Interferon gamma signaling
14	GPBAR1	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	GPCR signaling
15	ITGA4	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	GPCR signaling, PPAR pathway, FAK1 signaling, Focal adhesion, Actin Nucleation, and branching
16	F3	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	Formation of fibrin clot, AGE-RAGE signaling pathway, complement, and coagulation cascades
17	SELE	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	AGE-RAGE signaling pathway, Cell adhesion molecules, VEGF Signaling
18	SPP1	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	FAK1 signaling, ERK signaling, Toll-like receptor signaling pathway, ECM receptor interaction, Focal adhesion
19	IL1R1	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	PEDF Signaling, Toll-like receptor signaling pathway, TGF-Beta Pathway
20	ELANE	UC, CD, Arthritis, Uveitis, PSC, and Pyoderma Gangrenosum	Degradation of extracellular matrix, Innate immune system, Transcriptional misregulation in cancer
21	IL20	UC,CD, Arthritis, Uveitis, and PSC	PEDF, TGF beta, AKT signaling, Rho family Gtpase, PAK pathway
22	IL21	UC, CD, Arthritis, Uveitis, and PSC	PEDF, Rho Gtpase, PAK, AKT, Th17
23	IL2RA	UC, CD, Arthritis, Uveitis, and PSC	Apoptosis, IL-receptor SHC signaling, PEDF pathway, TGF Beta, AKT
24	SAG	UC, CD, Arthritis, Uveitis, and PSC	Rhodopsin mediated signal pathway
25	IFNG	UC, CD, Arthritis, Uveitis, and PSC	Allograft rejection, Immune response INF γ signaling pathway, Toll Pathway
26	CXCR3	UC,CD, Arthritis, Uveitis, and PSC	Class A/1, GPCR, Neuropeptide signaling, AKT
27	CXCL10	UC, CD, Arthritis, Uveitis, and PSC	PEDF, Class A/1 receptor, Rho family GTPase, Toll like receptor
28	CTLA4	UC, CD, Arthritis, Uveitis, and PSC	PKC-theta, CD28, Cell adhesion molecules
29	CCL2	UC, CD, Arthritis, Uveitis, and PSC	PEDF, TGF beta, AKT, and Rho
30	LTA	UC, CD, Arthritis, Uveitis, and PSC	PEDF, Rho, TRAF, NF-Kb
31	IL10	UC, CD, Arthritis, Uveitis, and PSC	PEDF, TGF, Rho, AKT
32	CCR5	UC, CD, Arthritis, Uveitis, and PSC	HIV Receptor-Class A1, Akt, GPCR, Neuropeptide, and Chemokine
33	RBP3	UC, CD, Arthritis, Uveitis, and PSC	Visual cycle, metabolism of fat-soluble vitamins, GPCR signaling
34	CXCR1	UC, CD, Arthritis, Uveitis, and PSC	IL8-R pathway-Class A/1, GPCR, Neuropeptide signaling, Cell Adhesion ECM modeling, Inhibitory actions of lipoxins on SOD
35	FASLG	UC, CD, Arthritis, Uveitis, and PSC	Apoptosis and Death receptor
36	TNFRSF1A	UC, CD, Arthritis, Uveitis, and PSC	TWEAK, Apoptosis, TGF, PEDF
37	TLR4	UC, CD, Arthritis, Uveitis, and PSC	TRAF, Toll like receptor pathway
38	IL2RB	UC, CD, Arthritis, Uveitis, and PSC	PEDF, AKT, TGF-beta, IL22 pathway
39	NLRC4	UC, CD, Uveitis, and Arthritis	Gene Expression, innate immune system, Legionellosis, and NLR signaling
40	SLC22A4	UC, CD, Arthritis, and PSC	Phospholipase D signaling pathway, Transport of metal ions, glucose, bile salt, and organic acids
41	AREG	UC, CD, Arthritis, and PSC	TGF Beta, Rho Gtpases, Nanpg on mammalian ESC pluriopotency
42	IL25	UC,CD, Arthritis, and Pyoderma Gangrenosum	IL17 signaling pathway, PEDF induced signaling, TH2 differentiation
43	MON2	UC,CD, Arthritis, and Pyoderma Gangrenosum	Regulates endosome to golgi trafficking
44	FASN	UC, CD, and Arthritis	AMPK signaling pathway, Fatty acid biosynthesis, Fatty acid metabolism, Insulin signaling pathway, Metabolic pathways
45	LZTR1	UC, CD, and Arthritis	Protein modification and ubiquitination
46	LAMP2	UC, CD, and Arthritis	Autophagy, Platelet, and Neutrophil degranulation
47	ALOX5	UC, CD, and Arthritis	arachidonic acid, LT, Selenium pathway
48	SLCO1B3	UC, CD, and Pyoderma Gangrenosum	Bile acid, bile salt metabolism

Notes: *Source – Kegg pathway database (https://www.genome.jp/kegg/pathway.html); UniProt (https://www.uniprot.org/) and Genecards – the human genome database (https://www.genecards.org/).26–28

Abbreviations: UC, ulcerative colitis; CD, Crohn’s disease; PSC, primary sclerosing cholangitis; IL-17A, interleukin 17A; NOD2, nucleotide binding oligomerization domain containing 2; TNF, tumor necrosis factor; CCR6, C-C motif chemokine receptor 6; CXCL8, C-X-C motif chemokine ligand 8; 1L1B, interleukin 1 beta; NLRP3, NLR family pyrin domain containing 3; MPO, myeloperoxidase; IL1RN, interleukin 1 receptor antagonist; ITGB2, integrin subunit beta 2; PTPN22, protein tyrosine phosphatase non-receptor type 22; MMP9, matrix metallopeptidase 9; ICAM1, intercellular adhesion molecule 1; GPBAR1, G protein-coupled bile acid receptor 1; ITGA4, integrin subunit alpha 4; F3, coagulation factor III, tissue factor; SELE, selectin E; SPP1, secreted phosphoprotein 1; IL-1R1, interleukin 1 receptor type 1; ELANE, elastase, neutrophil expressed; IL-20, interleukin 20; IL-21, interleukin 21; IL-2RA, interleukin 2 receptor subunit alpha; SAG, S-antigen visual arrestin; IFNG, interferon gamma; CXCR3, C-X-C motif chemokine receptor 3; CXCL10, C-X-C motif chemokine ligand 10; CTLA4, cytotoxic T-lymphocyte associated protein 4; CCL2, C-C motif chemokine ligand 2; LTA, lymphotoxin alpha; IL10, interleukin 10; CCR5, C-C motif chemokine receptor 5; RBP3, retinol binding protein 3; CXCR1, C-X-C motif chemokine receptor 1; FASLG, Fas ligand; TNFRSF1A, TNF receptor superfamily member 1A; TLR4, toll like receptor 4; IL2RB, interleukin 2 receptor subunit beta; NLRC4, NLR family CARD domain containing 4; SLC22A4, solute carrier family 22 member 4; AREG, amphiregulin; IL25, interleukin 25; MON2, MON2 homolog, regulator of endosome-to-golgi trafficking; FASN, fatty acid synthase; LZTR1, leucine zipper like transcription regulator 1; LAMP2, lysosomal associated membrane protein 2; ALOX5, arachidonate 5-lipoxygenase; SLCO1B3, solute carrier organic anion transporter family member 1B3; CF, cystic fibrosis; IL-6, interleukin 6; IL-17, interleukin 17; IL-27, interleukin 27; PDGF, platelet derived growth factor; RA pathway, retinoic acid pathway; NF-kappaB, nuclear factor kappa light chain enhancer of activated B cells; NOD, nucleotide binding oligomerization domain; STAT 3, signal transducer and activator of transcription 3; AKT, protein kinase B; GPCR, G protein coupled receptor; PEDF, pigment epithelium derived factor; TGF–Beta, transforming growth factor beta; ERK, extracellular signal regulated kinase; NLR, nod like receptor; MAPK, mitogen activated protein kinase; PPAR, peroxisome proliferator-activated receptors; FAK1, focal adhesion kinase 1; PAK, P21 activated protein kinase; VCAM-1, vascular cell adhesion molecule 1; AGE, advanced glycation end products; RAGE, receptor for advanced glycation end products; Rho family, Ras homolog family; Class A/1, rhodopsin like receptors; PKC, protein kinase C; HIV, human immunodeficiency virus; IL-8, interleukin 8; ECM, extracellular matrix; SOD, superoxide dismutase; TWEAK, TNF related weak inducer of apoptosis; TRAF, tumor necrosis factor receptor associated factor; ESC, embryonic stem cells; AMPK, AMP activated protein kinase; LT, leukotriene.

Figure 1 Signaling map of genes (interactome) overlapping in inflammatory bowel disease (UC and CD) and its extra-intestinal manifestations.

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