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Human Genetic Diseases Periodic fever syndrome (TRAPS) associated with heterozygous extracellular mutations. Autosomal hyper-IgM syndrome associated with loss-of function mutations Locus associated with rheumatoid arthritis (RA) through GWAS Autoimmune lymphoproliferative syndrome (ALPS) associated with heterozygous dominant-interfering mutations Associated with inflammatory bowel disease (IBD) in GWAS Locus associated with ulcerative colitis in GW

Phenotype associated With Deficiency Resistance to TNF-induced arthritis models, resistant to endotoxic shock, increased sensitivity to bacterial pathogens Still susceptible to TNF- induced arthritis models, defective CD8T-cell apoptosis after restimulation, increased sensitivity to bacterial pathogens No LN, PP, defective GC formation Defective CD4 T-cell responses Defective immunoglobulin (Ig) class switching and germinal center formation
TNF Superfamily receptors (receptors in Italics Have a C-Terminal Death Domain)

Key Functions Mediates TNF-induced inflammation (and apoptosis in some cells) May enhance proapoptotic effect of TNFR1 Lymphoid organ formation T-cell costimulation Costimulation and differentiation of B cells and antigen-presenting cells (APCs) Apoptosis of restimulated CD4 T cells, B cells, ?others Soluble decoy receptor for FasL, LIGHT, and TL1A May have a role in tumor immune evasion T-cell costimulation ?Inhibition of CD8 T-cell e

OMIM ID 191190 191191 600979 600315 109535 134637 603361 186711 153243 602250 603611 603612 603613

Binds to Ligand(s) TNF-α (2), Ltα (1) TNF-α (2), Ltα (1) LIGHT (14), LTβ (3) OX40L (4) CD40L (5) FasL (6) FasL (6), TL1A (15), LIGHT (14) CD27L (7) CD30L (8) 4-1BBL (9) TRAIL (10) TRAIL (10) TRAIL (10)

FPF, p55, p60, TBP1, TNF-R, TNFAR, TNFR1, p55-R, CD120a, TNFR55, TNFR60, TNF-R-I, TNF-R55, p75, TBPII, TNFBR, TNFR2, CD120b, TNFR80, TNF-R75, p75TNFR, TNF-R-II LTBR, CD18, TNFCR, TNFR-RP, TNFRSF3, TNFR2-RP, LT-BETA-R, OX40, ACT35, CD134, p50, Bp50, CD40, CDW40, MGC9013 FAS, APT1, CD95, APO-1 M68, TR6, DCR3, DJ583P15.1.1 T14, CD27, S152, Tp55, CD30, KI-1, D1S166E ILA, 4-1BB, CD137, CDw137, MGC2172 DR4, APO2, MGC9365, TRAILR1

aliases MGC19588 TNF-R-III TXGP1L MGC20393 TRAILR3

Common Name(s) Tumor necrosis factor receptor 1 (TNF-R1) Tumor necrosis factor receptor 2 (TNF-R2) Lymphotoxin β receptor OX40 CD40 Fas, CD95 Decoy receptor 3 CD27 CD30 4-1BB, CD137 Death Receptor 4 (DR4) Death Receptor 5 (DR5) Decoy receptor 1

TABLE 9.3 Symbol TNFRSF1A TNFRSF1B TNFRSF3 TNFRSF4 TNFRSF5 TNFRSF6 TNFRSF6B TNFRSF7 TNFRSF8 TNFRSF9 TNFRSF10A TNFRFRSF10B TNFRSF10C