Table 2.

Polymorphisms and mutations in genes encoding co-receptors, signalling proteins, transcription factors and cytokines/chemokines that are associated with human diseases

Gene	Chromosome	Disease association	Protein	Function in B cells	Reference
PTPN22	1p13.2	RA, SLE, GT, T1D	LYP	Lymphocyte-specific tyrosine phosphatasea	[47]
NCF2	1q25	SLE	p67phox	Subcomponent of NADPH oxidase, ROS generationa	[48]
IL10	1q31-q32	SLE, UC, T1D	IL-10	Anti-inflammatory cytokinea	[49]
PTPRC	1q31.3-q32.1	SLE, RA, MS, T1D	CD45	Membrane protein tyrosine kinases	[50]
FCGR2A	1q23.2	SLE, RA	IGFR2	Low-affinity IgG FC receptora	[51, 52]
RASGRP3	2p25.1-p24.1	SLE	GRP3	Signalling downstream of the BCRa	[53]
BANK1	4q24	SLE, SSc, RA	BANK1	Scaffold protein involved in BCR signalling	[54]
IL21	4q27	SLE, PSO, CEL	IL-21	Cytokine, class switch recombination, plasma cell differentiationa	[55]
BACH2	6q15	SLE, AS, ATD, CEL, CD, MS, T1D, IBD, PSC	BACH2	Negative regulator of transcriptiona	[50]
PRDM1-ATG5	6q21	SLE, RA, CD	Blimp1	Differentiation and development of plasma cellsa	[49]
IKZF1	7p12.2	SLE, CD	Ikaros	TF, differentiation, development, self-tolerancea	[53]
BLK	8p23-p22	SLE, SS, RA, SSc, pAPS	BLK	Tyrosine kinase, BCR signalling, development	[56]
LYN	8q12	SLE	Lyn	Tyrosine protein kinase, BCR signalling	[4, 57]
CCL21	9q13.3	RA	CCL21	Chemokine, germinal centre formation	[58]
ETS1	11q23.3	SLE	Ets1	TF, negative regulator of differentiationa	[59]
CXCR5	11q23.3	SS	CXCR5	Chemokine receptor, migration to B cell folliclesa	[60]
SLC15A4	12q24.32	SLE	PTR4	Proton-coupled amino-acid transporter located in endolysosomes, autoantibody productiona	[53, 61]
ELF1	13q13	SLE	Elf1	TF, binding the IgH enhancera	[62]
CSK	15q24.1	SLE	Csk	Increases BCR-mediated activation of mature B cellsa	[63]
ITGAM	16p11.2	SLE	CD11B	Regulation of BCR signallinga	[64]
IRF8	16q24.1	SLE	IRF8	TF, cell developmenta	[65]
IKZF3	17q21	SLE	Aiolos	TF, downregulation of the pre-BCRa	[65]
CD40	20q13.12	RA	CD40	Co-stimulatory molecule, promotes antibody production	[58]
IKBKE	1q32.1	SLE	IKKI	Phosphorylates IκBαa	[50]
TNIP1	5q33.1	SLE, SS, PS	NAF1	TNFAIP3 interacting proteina	[49, 60]
TNFAIP3	6q23	SLE, SS, RA, T1D UC, CEL, PSO	A20	Ubiquitination and negative signalling regulator ubiquitin editing enzymea	[58, 60]
PRKCB	16p11.2	SLE	PRKCB1	Member of the PKC family, BCR-dependent NF-κB activationa	[66]
UBE2L3	22q11.21	SLE, CD, RA, CEL	UBE2L3	Ubiquinase, NFkB activation, plasmablast and plasma cell developmenta	[67]
IRAK1/MECP2	Xq28	SLE, RA	Irak1	TACI-dependent Ig class switching via MyD88a	[68, 69]
REL	2p16.1	RA	Rel	Survival and proliferationa	[70]
TRAF1	9q33.1	RA	Traf1	CD40 and TLR signallinga	[58]

The table lists polymorphic risk loci associated with the development of autoimmune diseases. The data are generated in GWAS and genes cited include those that encode proteins with known functions in B lymphocytes

RA rheumatoid arthritis, SLE systemic lupus erythematosus, GT Graves thyroiditis, T1D type 1 diabetes, CEL coeliac disease, MS multiple sclerosis, CD Crohn’s disease, PSO psoriasis, UC ulcerative colitis, AS ankylosing spondylitis, ATD autoimmune thyroid disease, JIA juvenile idiopathic arthritis, AA alopecia areata, IBD inflammatory bowel disease, PSC primary sclerosing cholangitis, SS Sjögren’s syndrome, SSc systemic sclerosis, TF transcription factor, BCR B cell receptor

^aNot specific for B cells