Table 3.

NOD-like receptors (NLR) and IBD. The proteins, the belonging families, functions and associated diseases are reported. MHC: major histocompatibility complex; NOD: Nucleotide-binding oligomerization domain; VAMAS1: Vitiligo-associated multiple autoimmune disease 1; MSPC: Multiple self-healing palmoplantar carcinoma; JRRP: Congenital juvenile recurrent respiratory papillomatosis; FMF: Familial Mediterranean Fever; FCAS: Familial cold autoinflammatory syndrome; AIADK: Autoinflammation with arthritis and dyskeratosis; MWS: Muckle-Wells syndrome; RA: Rheumatoid arthritis.

Family	Protein	Gene	Mutation-Related Diseases	IBD-Associated	Function	Complex
NLR	MHC class II transactivator	CIITA	Bare lymphocyte syndrome RA	Unknown	Positive regulator of class II MHC
NLRB	NRL family apoptosis inhibitory protein	NAIP	Spinal muscular atrophy	Unknown	Anti-apoptotic (inhibits CASP3, CASP7 and CASP9)	Sensor component of NLRC4 that recognizes and binds CprI from pathogenic bacteria C. violaceum
NLRC	NOD1	NOD1	IBD, Asthma, Behcet’s disease and sarcoidosis	Yes	Innate and adaptive immune responses and cellular homeostasis. Binds bacterial peptidoglycans, single-stranded RNA (ssRNA) from viruses and the metabolite sphingosine-1-phosphate	Interacts with RIPK2 activating NF-kB and MAPK signaling pathways
NLRC	NOD2	NOD2	Crohn’s disease and Blau syndrome	Yes	Innate and adaptive immune responses and cellular homeostasis. Binds LPS by recognizing the muramyl dipeptide (MDP), single-stranded RNA (ssRNA) from viruses and the metabolite sphingosine-1-phosphate	Interacts with RIPK2 activating NF-kB and MAPK signaling pathways. Interacts with NLRP1 leading to IL-1 release. Interacts with ATG16L1 leading to autophagy
NLRC	NOD-like receptor caspase recruitment domain containing proteins 3–5	NLRC3		Yes	Negative regulator of the innate immune response (negative regulation of NF-kB and type I interferon signaling pathways)	Prevents NLRP3 inflammasome formation and may affect NOD1- or NOD2-mediated NF-kB activation
		NRLC4	FCAS 4 Autoinflammation with infantile enterocolitis	Yes	Innate immune response. Promotes caspase-1 activation, cytokine production and macrophage pyroptosis	Homo-oligomerizes in the NLRC4 inflammasome and enters the NRLP3 inflammasome
		NRLC5	Pityriasis rubra pilaris Bare lymphocytic syndrome type I FMF	Unknown	Negative regulator of the innate immune response (negative regulation of NF-kB and type I interferon signaling pathways)
NLRP	NACHT, LRR, and PRD containing proteins 1–14	NLRP1-14	NRLP1: VAMAS1 MSPC JRRP	Yes	NLRP1: Innate immunity and inflammation. Cytokines IL-1, IL-18 and gasdermin-D (GSDMD), leading to pyroptosis, an inflammatory form of programmed cell death	NRLP1 inflammasome response to various pathogen-associated signals, recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation; may be activated by MDP in a NOD2-dependent manner
			NRLP3: FCAS1 AIADK MWS CINCA syndrome	Yes	NLRP3: regulation of inflammation, immune response, and apoptosis. Stimulated by extracellular ATP, reactive oxygen species, K(+) efflux, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, cytosolic dsRNA	NRLP3 inflammasome upstream activator of NF-kappaB signaling
			NLRP12: FCAS2	Yes	NLRP12 potent mitigator of inflammation Primarily expressed in dendritic cells and macrophages, inhibits both canonical and non-canonical NF-kB and ERK activation pathways Functions as a negative regulator of NOD2 by targeting it to degradation via the proteasome pathway. Promotes bacterial tolerance
NLRX	NOD-like receptor with “unknown” domain	NLRX1	Histiocytic sarcoma Combined oxidative phosphorylation deficiency 4 Mooren Ulcer Mitochondrial Complex V Nuclear deficiency Type 3	Unknown	Regulator of mitochondrial antivirus responses. Promotes autophagy Enhances NF-kB and JUN N-terminal kinase dependent signaling through the production of reactive oxygen species. Regulates energy metabolism in a sex-dependent manner	Regulates NLRP3 inflammasome activation to attenuate apoptosis

Data from GeneCard^®, The human gene database–https://www.genecards.org/ (accessed on 25 January 2023).