TNFRSF13B

Chr 17ADAR

TNF receptor superfamily member 13B

Also known as: CD267, CVID, CVID2, IGAD2, RYZN, TACI, TNFRSF14B

NCBI Gene: 23495 ENSG00000240505 UniProt: O14836 OMIM: 604907

The TNFRSF13B protein is a lymphocyte-specific receptor that binds APRIL and BAFF ligands to regulate B- and T-cell function and humoral immunity through activation of transcription factors including NF-AT, NF-kappa-B, and AP-1. Mutations cause common variable immunodeficiency and IgA deficiency, with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene shows high tolerance to loss-of-function variants (high LOEUF score), suggesting variable penetrance or that some variants may act through alternative mechanisms.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily. It interacts with calcium-modulator and cyclophilin ligand (CAML). The protein induces activation of the transcription factors NFAT, AP1, and NF-kappa-B and plays a crucial role in humoral immunity by interacting with a TNF ligand. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 1.962 OMIM phenotypes

Clinical Summary— TNFRSF13B

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Gene-Disease Validity (ClinGen)

immunodeficiency, common variable, 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.96LOEUF

pLI 0.000

Z-score -2.17

OE 1.73 (1.14–1.96)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.20Z-score

OE missense 1.26 (1.13–1.41)

215 obs / 170.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.73 (1.14–1.96)

0≤0.351.4

Missense OE?1.26 (1.13–1.41)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 18 / 10.4Missense obs/exp: 215 / 170.8Syn Z: -0.99

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongTNFRSF13B-related immunodeficiency, common variableLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6358th %ile

GOF

0.6540th %ile

LOF

0.4038th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNAlthough TNFRSF13B supports host defense, dominant-negative TNFRSF13B alleles are common in humans and other species and only rarely associate with disease.1

GOFA gain-of-function mutation in TNFRSF13B is a candidate for predisposition to familial or sporadic immune thrombocytopenia.2

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References