TNFRSF13B

Chr 17ADAR

TNF receptor superfamily member 13B

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 1.962 OMIM phenotypes
Clinical SummaryTNFRSF13B
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Gene-Disease Validity (ClinGen)
immunodeficiency, common variable, 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
137 unique Pathogenic / Likely Pathogenic· 206 VUS of 496 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.96LOEUF
pLI 0.000
Z-score -2.17
OE 1.73 (1.141.96)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.20Z-score
OE missense 1.26 (1.131.41)
215 obs / 170.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.73 (1.141.96)
00.351.4
Missense OE1.26 (1.131.41)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 18 / 10.4Missense obs/exp: 215 / 170.8Syn Z: -0.99
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTNFRSF13B-related immunodeficiency, common variableLOFAR

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

DN
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.PMID:34111031
GOFA gain-of-function mutation in TNFRSF13B is a candidate for predisposition to familial or sporadic immune thrombocytopenia.PMID:28834165

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

ClinVar Variant Classifications

496 submitted variants in ClinVar

Classification Summary

Pathogenic127
Likely Pathogenic10
VUS206
Likely Benign111
Benign18
Conflicting23
127
Pathogenic
10
Likely Pathogenic
206
VUS
111
Likely Benign
18
Benign
23
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
0
104
0
127
Likely Pathogenic
9
0
1
0
10
VUS
14
169
19
4
206
Likely Benign
0
8
29
74
111
Benign
0
2
11
5
18
Conflicting
23
Total4617916483495

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TNFRSF13B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗