Table 6.

IgAN susceptibility loci discovered in genome-wide association studies (GWAS).

Locus	Gene	Function
1p13	VAV3	Chemokine signaling; NK, T cells, B cells, FcεRI, FcγR. VAV proteins are essential for adaptive immune function and NF-κB activation in B cells, i.e., a process that stimulates IgA production
1q32	CFHR1, CFHR3	Complement system; encode Factor H related peptides that modulate the activity of the alternative complement pathway. FHR1 competes with factor H for binding to surface-fixed C3b leading to activation of C3 convertase
6p21	HLA-DQA1, HLA-DQB1, HLA-DRB1 PSMB8, PSMB9, TAP1, TAP2	MHC class II molecules critical for antigen processing and presentation and adaptive immunity Phagosome pathway
8p23	DEFA1, DEFA3, DEFA4, DEFA5, DEFA6	Innate immunity; antimicrobial peptides in mucosal defense; α-defensins 1,3,4 are synthesized in neutrophils, while α-defensins 5 and 6 are constitutively produced by the Paneth cells in the small intestine
8q22.3	ODF1-KLF10	Encodes a transcriptional repressor that acts as an effector of TGFβ signaling
9q34	CARD9	Innate immunity; NOD-like receptor signaling
11p11.2	ACCS	Encodes a1-aminocyclopropane-1-carboxylate synthase homologue that interact with a protein required for epithelial cell polarization and ciliogenesis
16p11	ITGAM, ITGAX	Encode leukocyte-specific α-integrins involved in the process of phagocytosis and regulation of IgA production
17p13	TNFSF13	Encode APRIL, a B cell stimulating cytokine induced by intestinal bacteria and promotes CD40-independent IgA class switching
22q12	LIF, OSM, HORMAD2, MTMR3	Cytokine-cytokine interaction; cytokine encoding genes expressed in mucosal tissues with immunomodulatory properties JAK-STAT signaling pathway
3q27.3	ST6GAL1	Encode enzyme ST3Gal-1 responsible for sialylation of Gal
7p21.3	C1GALT1	Encode enzyme C1GalT1 that catalyzes attachment of Gal to GalNAc
Xq24	C1GALT1C1	Encode chaperone Cosmc, required for the stability of C1GalT1 enzyme