Alt. symbols: TACI | CD267 | IGAD2

Approved name: TNF receptor superfamily member 13B
Alt. names: tumor necrosis factor receptor superfamily, member 13B

Location: 17p11.2: 16929816 - 16972118 (-)
Gene type: protein_coding, 7 transcripts.

Scores: LoFtool: 0.218000 | pLI: 0.00000000 | LOEUF: 1.958

HGNC: 18153

NCBI: 23495, RefSeq: NG_007281.1

Ensembl: ENSG00000240505.9

LRG_120 | Status: public

OMIM: 604907

Expression | ProteinAtlas

TNFRSF13B encodes TACI, a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily that plays a role in the stimulation of B- and T-cell function and the regulation of humoral immunity. TACI binds both TNFSF13/APRIL and TNFSF13B/TALL1/BAFF/BLYS ligands with similar high affinity. Ligand activation induces downstream calcineurin-dependent activation of NF-AT, as well as activation of NF-kappa-B and AP-1 family transcription factors. TACI stimulation has been shown essential for T-independent- but not for T-cell-dependent B cell responses (PMID 33679786).

Monoallelic or biallelic frameshift, missense, nonsense and splice site mutations in TNFRSF13B are associated with a form of Common Variable Immunodeficiency (CVID) [OMIM: 240500] as well as selective IgA deficiency [OMIM: 609529]. However, many variants show incomplete penetrance and can be found in many asymptomatic carriers, or are considered risk alleles. TNFRSF13B has a greater number of missense variants than it would be predicted by a sequence-context-based mutational model, as well as m ore observed than expected loss of function variants (stop gain and splice site variants), indicating a high tolerance to these mutations (pLI = 0.00, where pLI of 1 is the most intolerant) [Genome Aggregation Database, v2.1.1]. Most common variants are phenotypically dominant, either as dominant negatives or by causing haplo-insufficiency, but how they affect receptor signaling and function remains unclear. Additionally, TACI is expressed as two isoforms that differ by the presence (long, L) or absence (short, S) of exon 2, which is alternatively spliced following B cell activation (PMID 25631768). The short version lacks the cysteine rich domain 1 (CDR1) thought to mediate ligand binding, but the absence of this domain does not preclude receptor trimerization or subsequent signaling. TNFRSF13B-S requires a lower ligand concentration to signal than TNFRSF13B-L, in part due to increased ligand binding affinity. In contrast, certain mutations - C104R, A181E, and S194X – have been shown to result in receptors with impaired or no signaling (PMID 30333819). [Load More]